Title of Invention: Methods for lyoprotecting a macromolecule using tricine Abstract: This invention relates to lyoprotection agents for protecting macromolecules during lyophilization or freeze-drying. In particular, methods for use of these lyoprotectants in conjugate formulations are disclosed. Additionally, this invention describes lyophilized instant kit formulations for the radiolabeling of pharmaceuticals and/or macromolecules. Detailed Description: Part PAC: 5. DETAILED DESCRIPTION OF THE INVENTION Part PAC_2: 5.1. Novel Lyoprotectants Part PAR: According to one embodiment, the invention comprises a novel lyoprotectant/filler or bulking agent for macromolecules, which encompass proteinaceous materials, including peptide, polypeptide, protein, glycoprotein and proteoglycan substances. Lyophilized or freeze-dried products, such as proteins, require a bulking agent/lyoprotectant that forms a cake that is instantly soluble upon rehydration which protects the product from damage due to freezing and/or dehydration. Specifically, the purpose of the lyoprotectant is to insure that the lyophilized macromolecule does not aggregate upon rehydration and that the product substantially retains its biological/pharmaceutical activity. "Lyoprotectants" have been understood to function as such as a result of their tendencies to develop, and to persist in the form of glass-like concentrates (in which, for example, protein molecules are safely incorporated). Lyoprotection is lost if the lyoprotectant crystallizes. Part PAR_2: This embodiment of the present invention is based on the discovery that a compound having the formula: EQU (R.sup.3)(R.sup.4)(R.sup.5)C--N(R)--C(R.sup.1)(R.sup.2)--(CH.sub.2).sub.n --COOH Part PA1: where R is hydrogen, hydroxy, alkyl, hydroxyalkyl, or alkylcarboxy, or R and R.sup.1 together may form a mono-, di-, tri-, or tetra-methylene radical, or R and R.sup.2 together may form a mono-, di-, tri-, or tetra-methylene radical, and PA1 R.sup.1 and R.sup.2 may be the same or different and are selected from hydrogen, hydroxy, alkyl, hydroxyalkyl, carboxy, alkylcarboxy, alkylamine, alkylthiol and aryl or R.sup.1 and R.sup.2 together may form a tetra- or penta-methylene radical, and PA1 R.sup.3 and R.sup.4 and R.sup.5 may be the same or different and are selected from hydrogen, hydroxy, alkyl, hydroxyalkyl, carboxy and alkylcarboxy, provided that at least one of R.sup.3, R.sup.4 and R.sup.5 is hydroxyalkyl, and PA1 n is equal to 0, 1 or 2, PA1 where R is hydrogen, hydroxy, alkyl, hydroxyalkyl, or alkylcarboxy, or R and R.sup.1 together may form a mono-, di-, tri-, or tetra-methylene radical, or R and R.sup.2 together may form a mono-, di-, tri-, or tetra-methylene radical, and PA1 R.sup.1 and R.sup.2 may be the same or different and are selected from hydrogen, hydroxy, alkyl, hydroxyalkyl, carboxy, alkylcarboxy, alkylamine, alkylthiol and aryl or R.sup.1 and R.sup.2 together may form a tetra- or penta-methylene radical, and PA1 R.sup.3 and R.sup.4 and R.sup.5 may be the same or different and are selected from hydrogen, hydroxy, alkyl, hydroxyalkyl, carboxy and alkylcarboxy, provided that at least one of R.sup.3, R.sup.4 and R.sup.5 is hydroxyalkyl, and PA1 n is equal to 0, 1 or 2. PA1 E is an alkenyl group or represents H.sub.2 in which case the compound is in an acid addition salt form, PA1 NNH is a hydrazyl fragment PA1 Py is a fragment of pyridine, C.sub.5 H.sub.3 N PA1 J is selected from the group consisting of --CO--NH, --CO--O--, --CO--S-- and --NH--CO--, PA1 T is an alkylene chain or, if J is --CO--NH--, T is the residue of an amino acid moiety, PA1 Q is a hydrophilic or cleavable moiety, and PA1 Z is an amine- and/or thiol reactive moiety. PA1 1. the molecule in which E represents H.sub.2, J is the group C(.dbd.O)--O, and bound to the oxygen of J is the fragment (CH.sub.2).sub.3 --O--C(.dbd.O)--CH.sub.2 --Br. ##STR2## 2. the molecule in which E represents H.sub.2, J is the group --C(.dbd.O)--NH--, and bound to the NH group of J is the fragment --C--(--(CH.sub.2).sub.2 --C(.dbd.O)--OH)--C(.dbd.O)--O--(CH.sub.2).sub.3 --O--C(.dbd.O)--CH.sub.2 --Br ##STR3## 3. the molecule in which E represents H.sub.2, J is the group --C(.dbd.O)--NH--, and bound to the NH group of J is the fragment --(CH.sub.2).sub.2 --S--C(.dbd.O)--(CH.sub.2)--Br. ##STR4## PA1 D is an alkyl backbone, cyclic alkyl backbone or aryl backbone group having the NHCSNHR groups at the 1,2-, 1,3-, 1,4-, or 1,5- (etc.) positions, and PA1 R is H or a substituent with the general formula: ##STR6## in which a=0 or 1 PA1 b=0 to 10 PA1 c=0 or 1 PA1 if c=1 then, Y=S, O or H.sub.2 PA1 d=0 to 2 PA1 e=0 to 10 and PA1 Z=--H, --N(R').sub.3 !.sup.+ X.sup.-, --SO.sub.3 H, --COOH, --OH, H.sub.2 PO.sub.3 ; PA1 where R is hydrogen, hydroxy, alkyl, hydroxyalkyl, or alkylcarboxy, or R and R.sup.1 together may form a mono-, di-, tri-, or tetra-methylene radical, or R and R.sup.2 together may form a mono-, di-, tri-, or tetra-methylene radical, and PA1 R.sup.1 and R.sup.2 may be the same or different and are selected from hydrogen, hydroxy, alkyl, hydroxyalkyl, carboxy, alkylcarboxy, alkylamine, alkylthiol and aryl or R.sup.1 and R.sup.2 together may form a tetra- or penta-methylene radical, and PA1 R.sup.3 and R.sup.4 and R.sup.5 may be the same or different and are selected from hydrogen, hydroxy, alkyl, hydroxyalkyl, carboxy and alkylcarboxy, provided that at least one of R.sup.3, R.sup.4 and R.sup.5 is hydroxyalkyl, and PA1 n is equal to 0, 1 or 2. Part PAL: is a very effective lyoprotectant and bulking agent for macromolecules or macromolecular compositions. Part PAR_3: Preferred alkyl and substituted alkyl groups for R are alkyl of 1 to 3 carbon atoms. Preferably, when R.sup.1 and R.sup.2 are alkyl or substituted alkyl, they are 1 to 4 carbon atoms. Preferred aryl groups are phenyl and benzyl. Preferably, when R.sup.3 and R.sup.4 and R.sup.5 are alkyl or substituted alkyl groups they are 1 to 3 carbon atoms. Part PAR_4: Preferably, at least one of R, R.sup.1 and R.sup.2 is hydrogen and at least one of R.sup.3, R.sup.4 and R.sup.5 is hydroxymethyl. Other desirable compounds are those in which R, R.sup.1 and R.sup.2 are all hydrogen, R.sup.3 is hydrogen, methyl or ethyl, and R.sup.4 and R.sup.5 are hydroxymethyl or 2-hydroxyethyl; R, R.sup.1 and R.sup.2 are all hydrogen, R.sup.3 and R.sup.4 are hydrogen or methyl, and R.sup.5 is hydroxymethyl or 2-hydroxyethyl. Also desirable are compounds in which R and R.sup.1 are both hydrogen, R.sup.2 is methyl hydroxy, hydroxymethyl, carboxy, carboxymethyl, 2-carboxyethyl, phenyl, benzyl, 1-hydroxyethyl or mercaptomethyl, and R.sup.3, R.sup.4 and R.sup.5 are all hydroxymethyl; R is hydrogen, R.sup.1 and R.sup.2 are both methyl, and R.sup.3, R.sup.4 and R.sup.5 are all hydroxymethyl; R is hydroxy, hydroxymethyl, or carboxymethyl, R.sup.1 and R.sup.2 are both hydrogen, and R.sup.3, R.sup.4 and R.sup.5 are all hydroxymethyl. Part PAR_5: In a preferred embodiment the compound is N-tris(hydroxymethyl)methyl!glycine, also known as tricine. In this preferred embodiment tricine, is used at a pH value in which the buffering capacity of tricine is of no value. The range at which tricine is an effective buffer is about pH 7.15-9.15. The preferred pH for the specific embodiments of the invention is about pH 5. Further, tricine is also used in amounts of 10-200 mg/ml, which is typically more than those amounts used when tricine is used as a buffer. Part PAR_6: Supporting the findings of this discovery are the results of thermal analyses and freezing microscopy studies, in which it was found that tricine is more difficult than mannitol to crystalize, see Section 6.1, infra. Differential thermal analysis (DTA) and Electrical Resistance (ER) measurements demonstrated the characteristic freezing/thawing behavior of an aqueous tricine solution. These studies revealed the development and persistence of a concentrated amorphous tricine phase in the presence of ice and the subsequent softening of that phase during warming. Correspondingly, they did not reveal any of the thermal behavior associated with the crystallization of a dissolved solute or of its subsequent eutectic melting. Eutectic behavior was very obviously absent. The T.sub.g ', the temperature at which the glassy tricine concentrate softens abruptly was seen close to, and a little above -40.degree. C. The behavior upon cooling of an aqueous tricine solution observed by cryomicroscopy techniques (see A. P. MacKenzie, 1975, In:Freeze Drying and Advanced Food Technology, Goldblith et al., (Eds.), Academic Press, NY) failed to reveal any crystallization of tricine. Concentrated amorphous aqueous tricine persisted as such at all temperatures to -20.degree. C. By freeze-drying microscopy, an aqueous tricine solution was seen to proceed with retention at -50, -45 and -40.degree. C. and with collapse at -35 and -30.degree. C. All experiments point to a consistent freezing/thawing behavior of aqueous tricine solutions that make it a desirable cryoprotectant. An aqueous solution of tricine will crystallize only under extreme conditions and when the solution has been seeded with dry tricine. This observed crystallization proceeds very slowly, too slowly to allow crystallization during a normal freezing cycle during lyophilization (see for example Section 6.1). Part PAR_7: Lyophilization processes are well known in the art and an appropriate lyophilization cycle could easily be designed based on the data presented in the Examples, see infra. For example, FIG. 1 shows an illustrative lyophilization cycle that results in an acceptable product. Preferably, however, the primary drying cycle would be about 6-20 hours, more preferably about 10-15 hours. Part PAR_8: According to one embodiment, tricine at 10-200 mg/ml is used as a lyoprotectant for macromolecules. Preferably, it is used in a range of about 18-150 mg/ml and most preferably 18-144 mg/ml. One simply mixes tricine with the desired macromolecule in an aqueous solution that optionally contains a buffer and the resultant mixture is lyophilized. Using tricine as a lyoprotectant, entails using it in a range of about 80% to about 99+% of the mixture of active ingredients, more preferably about 90% to about 99%, most preferably about 95% to about 99%. In a preferred embodiment, the solution containing the macromolecule is typically formulated outside of tricine's effective biological buffering range (approximately pH 7.15-9.15), preferably about pH 5. Part PAC_3: 5.2. One Pot Lyophilized Formulation and Kit Part PAR_9: Another embodiment of the present invention relates to novel compositions for the formation of a lyophilized formulation as well as an instant kit for the formation of a radiopharmaceutical. The radiopharmaceutical, which in a preferred embodiment is a radioconjugate, formed using the formulation or kit can be used for in vivo imaging or therapy. The lyophilized formulation or kit comprises a lyophilized mixture of the following components: a chemical reducing agent, a transchelator, and a conjugate of a linker and a targeting molecule. The kit may further comprise other kit components known to those skilled in the art. Part PAR_10: Solely for ease of explanation, the description of this embodiment of the invention is divided into the following sections: i) Chemical reducing agent; ii) Transchelator; iii) Linker; iv) Targeting molecule; and v) One pot method for lyophilization. Part PAL_2: 5.2.1. Chemical Reducing Agent Part PAR_11: The chemical reducing agent serves to reduce a radioisotope in an high oxidation state to a lower oxidation state, from which the radioisotope can be chelated by the transchelator and linker molecule. For use with Tc or Re, the reducing agent can be stannous ion (Sn.sup.+2), ferrous ion (Fe.sup.+2), or dithionite ion (S.sub.2 O.sub.4.sup.2-), also termed hydrosulfite. Most preferably, it is stannous ion formed from stannous chloride dihydrate. As a weight fraction of the weight of the active components of the kit, the stannous chloride dihydrate fraction preferably should be in the range 0.1% to 0.6%, most preferably in the range 0.1% to 0.2%. The active components of the kit do not take into account inert ingredients, vials, caps, packaging material and the like. The kits of the present invention advantageously permit lower than conventional amounts of reducing agent to be employed and provide a good stability profile for the reducing agent. Part PAL_3: 5.2.2. Transchelator Part PAR_12: The transchelator serves to hold chemically reduced radioisotopes in a lower oxidation state prior to association with the linker molecule. According to the present invention, the transchelator is a compound of the formula: EQU (R.sup.3)(R.sup.4)(R.sup.5)C--N(R)--C(R.sup.1)(R.sup.2)--(CH.sub.2).sub.n --COOH Part PAR_13: Preferred alkyl and substituted alkyl groups for R are alkyl of 1 to 3 carbon atoms. Preferably, when R.sup.1 and R.sup.2 are alkyl or substituted alkyl, they are 1 to 4 carbon atoms. Preferred aryl groups are phenyl and benzyl. Preferably, when R.sup.3 and R.sup.4 and R.sup.5 are alkyl or substituted alkyl groups they are 1 to 3 carbon atoms. Part PAR_14: Preferably, at least one of R, R.sup.1 and R.sup.2 is hydrogen and at least one of R.sup.3, R.sup.4 and R.sup.5 is hydroxymethyl. Other desirable compounds are those in which R, R.sup.1 and R.sup.2 are all hydrogen, R.sup.3 is hydrogen, methyl or ethyl, and R.sup.4 and R.sup.5 are hydroxymethyl or 2-hydroxyethyl; R, R.sup.1 and R.sup.2 are all hydrogen, R.sup.3 and R.sup.4 are hydrogen or methyl, and R.sup.5 is hydroxymethyl or 2-hydroxyethyl. Also desirable are compounds in which R and R.sup.1 are both hydrogen, R.sup.2 is methyl hydroxy, hydroxymethyl, carboxy, carboxymethyl, 2-carboxyethyl, phenyl, benzyl, 1-hydroxyethyl or mercaptomethyl, and R.sup.3, R.sup.4 and R.sup.5 are all hydroxymethyl; R is hydrogen, R.sup.1 and R.sup.2 are both methyl, and R.sup.3, R.sup.4 and R.sup.5 are all hydroxymethyl; R is hydroxy, hydroxymethyl, or carboxymethyl, R.sup.1 and R.sup.2 are both hydrogen, and R.sup.3, R.sup.4 and R.sup.5 are all hydroxymethyl. Part PAR_15: In the present invention, the transchelator functions additionally as a lyoprotectant and bulking agent. Most preferably, it is tricine, N-tris(Hydroxymethyl)methyl!glycine, C.sub.6 H.sub.13 NO.sub.5, chemical registry number 5704-04-1. Part PAR_16: As a weight fraction of the weight of the active components of the kit, the transchelator fraction should be in the range of about 80% to about 99+%, more preferably in the range of about 90% to about 99%, most preferably about 95% to about 99%. The active components of the kit do not take into account inert ingredients and other kit components such as vials, caps, packaging material and the like. Part PAL_4: 5.2.3. Linker Molecule Part PAR_17: The linker molecule serves to coordinately bind the radioisotope and to form a covalent bond to the targeting molecule. Additionally in the present invention, the linker molecule and/or the targeting molecule serve to protect the chemical reducing agent from oxidation, such that less reducing agent is required in the instant kit. There are two preferred classes of linker molecules, although others would be understood by those of average skill in the art having considered the present invention. Part PAR_18: First, as described in European Patent Application PCT WO 94/10149 and in Schwartz, D. A. et al., 1991, Bioconjugate Chem. 2:333-336, there are hydrazyl pyridine derivatives of the general form EQU ENNH-Py-J-T-Q-Z Part PAL_5: in which Part PAR_19: Where E is alkenyl, it may be straight or branched lower alkenyl, of up to four carbon atoms. Part PAR_20: The most preferred member of this class is the molecule in which E represents H.sub.2, J is the group --C(.dbd.O)--NH, and bound to the NH group of J is the fragment: --(CH.sub.2).sub.3 --O--C(.dbd.O)--CH.sub.2 --Br, as depicted below: ##STR1## Part PAR_21: Other preferred members of this class are the following: Part PAR_22: Second, as described in U.S. Pat. No. 5,326,856 and PCT publication WO93/21151, there are substituted thioureas of the formula: ##STR5## in which L contains functionality to link to the targeting molecule Part PA2: in which X- is a counteranion such as a halide or an acid anion and R' is a C1 to C4 lower alkyl. Part PAR_23: The most preferred member of this class is the molecule in which the NHCSNHR groups are in the 3,5 positions on a phenyl ring as depicted: ##STR7## R is NHC(.dbd.O)CH.sub.2 !N.sup.+ CH.sub.3).sub.3 ! X.sup.-, in which X.sup.- is a halide ion and L is an acid hydrazide. Part PAR_24: A preferred member of this class is the molecule in which the NHCSNHR groups are in the 3,5 positions, R is NHC(.dbd.O)CH.sub.2 !N.sup.+ CH.sub.3).sub.3 ! X.sup.-, in which X.sup.- is a halide ion and L is an acid hydrazide (linker BL14), see Coughlin and Belinka, U.S. Pat. No. 5,326,856. Another preferred member is as above except L is a carboxylic acid (linker BL1). Part PAR_25: The weight of (linker molecule+targeting molecule) as a fraction of the entire weight of the active components of the kit is in the range of about 1% to about 20%, most preferably about 2% to about 3%. The active components of the kit do not take into account inert ingredients and other kit components such as vials, caps, packaging material and the like. Part PAL_6: 5.2.4. Targeting Molecule Part PAR_26: The targeting molecule in the present invention is a subset of macromolecules having the ability to bind specifically to a target site and encompasses proteinaceous substances, including non-glycosylated proteins, glycoproteins, proteoglycans, etc., as well as peptidyl, polypeptidyl and glycopeptidyl substances. As such, the term includes polyclonal serum immunoglobulins, monoclonal antibodies, fragments of monoclonal antibodies having at least a portion of an antigen binding region including such as Fv, F(ab').sub.2, Fab, and Fab' fragments, single chain antibodies, chimeric or humanized antibodies, complementary determining regions (CDRs), etc., serum complement components, enzymes, cell surface histocompatibility antigens, cell surface receptors, receptor ligands, peptide or proteinaceous hormones, proteins or peptides which bind to cellular receptors, and molecular recognition units as that term is described in U.S. Pat. No. 5,196,510, incorporated herein by reference, and totally synthetic affinity reagents, as described in PCT/US94/00977, publication number WO94/18318, incorporated herein by reference. The targeting molecule has the ability to bind to a specific target and the targets encompass, for example, cells, tissues, organs, tumors and sites of infectious diseases, etc. These examples are merely illustrative and are not meant to limit the scope of possible targets. Part PAL_7: 5.2.5. One Pot Method for Preparing Lyophilized Formulation and Kit Part PAR_27: The present invention provides a method for preparing a formulation as well as an instant kit comprising mixing a chemical reducing agent, a transchelator, and a conjugate molecule in aqueous solution and lyophilizing the resulting solution or lyophilizing an aqueous mixture of chemical reducing agent, transchelator, and conjugate molecule. The lyophilized mixture may be stored for over one year without a significant loss in activity. The lyophilized formulation or instant kit is combined with an aqueous solution of a radioisotope, such as Tc or Re, and the conjugate is radiolabelled. Part PAR_28: Preferably, the chemical reducing agent comprises about 0.1% to 0.6% of the active components of the kit by weight, the transchelator comprises about 80% to 99+% of the active components of the kit by weight, and a conjugate, which comprises a targeting molecule covalently attached to a linker able to chelate a radiometal, such as Tc or Re and lyophilizing the mixture, comprises about a 1% to 4% fraction of the active components of the kit by weight. The active components of the kit do not take into account inert ingredients and other kit components such as vials, caps, packaging material and the like, known to those skilled in the art. Part PAR_29: The transchelator is a compound of the formula: EQU (R.sup.3)(R.sup.4)(R.sup.5)C--N(R)--C(R.sup.1)(R.sup.2)--(CH.sub.2).sub.n --COOH Part PAR_30: Preferred alkyl and substituted alkyl groups for R are alkyl of 1 to 3 carbon atoms. Preferably, when R.sup.1 and R.sup.2 are alkyl or substituted alkyl, they are 1 to 4 carbon atoms. Preferred aryl groups are phenyl and benzyl. Preferably, when R.sup.3 and R.sup.4 and R.sup.5 are alkyl or substituted alkyl groups they are 1 to 3 carbon atoms. Part PAR_31: Preferably, at least one of R, R.sup.1 and R.sup.2 is hydrogen and at least one of R.sup.3, R.sup.4 and R.sup.5 is hydroxymethyl. Other desirable compounds are those in which R, R.sup.1 and R.sup.2 are all hydrogen, R.sup.3 is hydrogen, methyl or ethyl, and R.sup.4 and R.sup.5 are hydroxymethyl or 2-hydroxyethyl; R, R.sup.1 and R.sup.2 are all hydrogen, R.sup.3 and R.sup.4 are hydrogen or methyl, and R.sup.5 is hydroxymethyl or 2-hydroxyethyl. Also desirable are compounds in which R and R.sup.1 are both hydrogen, R.sup.2 is methyl hydroxy, hydroxymethyl, carboxy, carboxymethyl, 2-carboxyethyl, phenyl, benzyl, 1-hydroxyethyl or mercaptomethyl, and R.sup.3, R.sup.4 and R.sup.5 are all hydroxymethyl; R is hydrogen, R.sup.1 and R.sup.2 are both methyl, and R.sup.3, R.sup.4 and R.sup.5 are all hydroxymethyl; R is hydroxy, hydroxymethyl, or carboxymethyl, R.sup.1 and R.sup.2 are both hydrogen, and R.sup.3, R.sup.4 and R.sup.5 are all hydroxymethyl. Part PAR_32: In the present invention, the transchelator functions additionally as a lyoprotectant and bulking agent. Most preferably, the transchelator/lyoprotectant/bulking agent is N-tris (hydroxymethyl) methyl! glycine, C.sub.6 H.sub.13 NO.sub.5, chemical registry number 5704-04-1. Preferably, the reducing agent is tin dichloride dihydrate. The lyophilized mixture can then be combined with an aqueous solution of radioactive metal, such as Tc or Re, wherein the linker chelates the radiometal. The aqueous solution can be water, saline, or any other pharmaceutically acceptable aqueous solution. This resultant radioactive mixture can then be used for in vivo treatment and/or diagnostics as well as for in vitro diagnostics. Part PAR_33: Additionally, as a consequence of using a transchelator, such as tricine, as a lyoprotectant, as well as a transchelator, the dissolution of the lyophilized powder is rapid and particulate free and the immunoreactivity of the conjugate is unchanged. Part PAR_34: In an embodiment of the instant kit, up to 10 mg/ml conjugate can be used in an instant kit formulation of the resent invention. Part PAR_35: In a preferred embodiment the instant kit is formed by mixing about 36 mg tricine, 50 .mu.g tin dichloride dihydrate, 0.2-1 mg conjugate, CYT-402 (Fab' fragment of mAb 15A8 covalently attached to linker BAHNH), 10 mM citrate, and 1 nM Na.sub.2 EDTA in about 1.0 ml total volume, at about pH 5, and lyophilizing the mixture in one pot. The lyophilized kit is stable for months. Part PAR_36: In another preferred embodiment, the instant kit comprises a lyophilized mixture of about 36 mg tricine, 50 .mu.g tin dichloride dihydrate, 0.2-1 mg conjugate, CYT 422 (7E11C5 mAb covalently attached to linker BL14), 10 mM citrate, and 1 mM Na.sub.2 EDTA at about pH 5 in one pot. Part PAR_37: In yet another preferred embodiment of the present invention, the instant kit comprises a lyophilized mixture of about 36 mg tricine, 50 .mu.g tin dichloride dihydrate, 0.2-1 mg conjugate, CYT 421 (Antibody B72.3 covalently attached to linker BL14), 10 mM citrate, and 1 mM Na.sub.2 EDTA at about pH 5 in one pot. Part PAR_38: The instant kit may further comprise inert ingredients and other kit components such as vials, packaging components and the like, which are well known to those skilled in the art. Part PAR_39: The lyophilized instant kit of the present invention tested against a prior art formulation is shown in FIG. 2. FIG. 2 demonstrates the difference in incubation time required to achieve &gt;95% incorporation of .sup.99m Tc by radioimmunoconjugate prepared using the lyophilized kit formulation of the present invention and by a fresh two pot method liquid formulation of the prior art. Part PAC_4: 6. Examples Part PAR_40: In order to more fully illustrate the nature of the invention and the manner of practicing the same, the following examples are provided, which are not to be construed as limiting the remainder of the disclosure or the scope of the invention in any way whatsoever. Part PAL_8: 6.1 Tricine as a Lyoprotectant Part PAR_41: According to the present invention, tricine is an excellent lyoprotectant since it is very difficult to crystallize dissolved tricine from frozen aqueous solutions. Thermal analyses demonstrated very clearly that a 20% w/w aqueous tricine solution froze and thawed without any eutectic behavior. Electrical resistance rose during freezing in a manner strongly characteristic of any system in which water separates as ice while solute continues merely to concentrate. Differential thermal analysis revealed a highly characteristic warming behavior of a sort always associated with the stepwise softening of a concentrated amorphous phase. Consecutive glass transitions were clearly identified. A first glass transition occurred between ca -60.degree. C. and ca -45.degree. C. and a second subsequent glass transition occurred between ca -40.degree. C. and ca -32.degree. C. In addition, a characteristic melting endotherm began at -25.degree. C. and ends at -2.degree. C. Glass transition temperatures were identified also from the electrical resistance recordings and seemed to correspond rather nicely to those determined by DTA. Part PAR_42: Similar results were found using cryomicroscopy and freeze-drying microscopy. A 5 .mu.l volume of a 5% wt/wt aqueous tricine solution was put on a cryomicroscope and frozen at -10.degree. C., with seeding by indirect contact with colder forceps. The frozen preparation was subjected to temperatures of -8, 10, -12.5, -15 and -20.degree. C. each for 15 to 30 minutes. The development of an ice phase and the attendant segregation of an implicitly concentrated aqueous tricine phase was observed. Intermittent observation failed to reveal any corresponding crystallization of tricine. No nucleation of any additional crystalline phase was detected at any time. Concentrated amorphous aqueous tricine appeared to persist as such at all temperatures to -20.degree. C. Next the sample was seeded with dry tricine crystals. Tricine crystal growth was seen to begin at the edge of the preparation and progressed very slowly beneath the glass cover slip. The tricine crystals dissolved during a warming cycle to -3.degree. C. and did not reappear when the preparation was again cooled. The freeze-drying process was also studied on a Freeze-Drying microscope. Freeze-drying of a 5% wt/wt aqueous tricine solution was seen to proceed with retention (fine structure was retained) at -50, -45, and -40.degree. C. and with collapse (fine structure was not retained) at -35 and -30.degree. C. Part PAR_43: All the experimental findings point to the consistent freezing/thawing behavior on the part of aqueous tricine solutions and to the further consistency of their freezing and freeze-drying behavior. Only a deliberate intervention altered the pattern. Aqueous tricine solutions froze with the development of an amorphous tricine concentrate that hardened to a glass with sufficient cooling, which could be softened with sufficient warming. One safely concludes that aqueous tricine solutions demonstrate: i) "non-eutectic" freezing, and ii) non-eutectic freeze-drying behavior governed by the properties of the amorphous tricine concentrate. Part PAC_5: 6.2 .sup.99m Tc Radioconjugate Prepared Using the One Pot Lyophilized Kit Part PAR_44: An instant kit was formulated for one step radiolabeling which on combination with .sup.99m Tc provided very fast labeling kinetics. The instant kit comprised a mixture of a reducing agent, i.e., tin dichloride dihydrate, a transchelator and lyoprotectant, i.e., tricine, and an immuno-conjugate. The conjugate was comprised of a targeting molecule, i.e., monoclonal antibody Fab' 15A8 White et al., 1985, Cancer Res. 45:1337-1343; Rosenstraus et al., 1991, Cancer Res. 51:5744-5751; U.S. Pat. No. 5,032,521! covalently attached to a linker molecule, in which the linker was a hydrazyl pyridine, i.e., BAHNH Schwartz et al., PCT WO 94/10149!, shown below. ##STR8## 6.2.1 .sup.99m mTc Incorporation Using the Lyophilized Instant Kit of the Invention Part PAR_45: F(ab').sub.2 fragments of 15A8 were generated by pepsin digestion of mAb 15A8 as previously described Rea et al., 1993, J. Immunol. Methods 157:165-173!. BAHNH (Acetic acid, bromo-,3-{(6-hydrazino-3-pyridinyl)carbonyl!amino}propyl ester monohydrobromide) was synthesized by Johnson-Matthey (West Chester, Pa.) as described in PCT WO 94/10149 and was used without further purification. Part PAR_46: Conjugation to form CYT-402: 15A8 F(ab').sub.2 fragments in PBS-EDTA (10 mM Phosphate, 150 mM NaCl, 1 mM EDTA, pH 7) were concentrated to 5-20 mg/ml using an Amicon.RTM. Centricon-10.RTM. concentrator (W. R. Grace & Co., Beverly, Mass.) or Amicon.RTM. Stirred Ultrafiltration Cell with a YM10 membrane. The conjugation was initiated by reduction of the F(ab').sub.2 with an 8 molar excess of dithiolthreitol (DTT) to Fab' for 14-18 hours at room temperature in the dark. The reduction was monitored by isocratic size exclusion HPLC using a TSK-3000 SW.sub.XL column (TOSOHASS, Philadelphia, Pa.) equilibrated with PBS/1 mM EDTA, pH 6. The DTT was not removed from the conjugation mixture after reduction. The reduced F(ab').sub.2 -DTT mixture was conjugated with a 3 molar excess of BAHNH to the DTT thiol content. BAHNH was added as a 30 mM-100 mM solution in water and the pH adjusted to 6.0 with 1 M NaOH. The F(ab')-DTT-BAHNH mixture was incubated for 16-23 garciamartha@example.org. C. after purging the reaction vessel with nitrogen or argon. The CYT-402 conjugate (15A8-Fab'-BAHNH) was purified from the mixture by size exclusion HPLC using a preparative or analytical grade Superose-12 column (Pharmacia, Piscataway, N.J.). The conjugation mixture load volumes were 3% of total bed volume. The column was eluted at a linear flow rate of 0.5 cm/min with 10-20 mM Na citrate, pH 5.0 containing 1-2 mM EDTA. The Fab'-BAHNH conjugate was concentrated to 2-5 mg/ml using an Amicons Centricons concentrator. The protein concentration of the samples was determined by either extinction coefficients of E.sub.280,mg/ml of 1.36 for 15A8-2a or by the Biorad Protein Determination Assay as described by the manufacturer using 15A8-2a protein reference standards. Part PAR_47: 4,4' DTDP Residual Thiol Assay: Samples to be examined were diluted in a total volume of 0.9 mL thiol assay buffer (100 mM Phosphate pH 7, 1 mM EDTA) and UV absorbance at 280 nm and 324 nm was determined. 100 .mu.L of 2 mM 4,4'-Dithiodipyridyl in water was added to the diluted sample and the absorbance at 324 nm was again determined. The thiol concentration was calculated using the published extinction coefficient of 4-thiol pyridone (E.sub.324,M =23,000) after subtraction of the pre-DTDP OD.sub.324 absorbance from the post-DTDP OD.sub.324 absorbance. The number of thiols per antibody fragment was determined by dividing the thiol concentration (.mu.M) by the protein concentration (.mu.M). Part PAR_48: o-Sulfonic Benzoic Acid Hydrazine Assay: Samples to be examined were diluted into 1 mL of o-sulfonic benzoic acid (Eastman Kodak, Rochester, N.Y.) 10.4 mg/100 mL 0.1 M acetate, pH 4.73. The hydrazine concentration was calculated using an extinction coefficient of E.sub.343.M =26,500. The molecular substitution ratio (MSR) of hydrazine conjugated to antibody was determined by dividing the hydrazine concentration (.mu.M) by the protein concentration (.mu.M) as determined by a Biorad protein determination assay. Part PAR_49: Radiolabeling of CYT-402: A mixture of CYT-402 conjugate, tin dichloride dihydrate, and tricine in an aqueous solution was lyophilized. The lyophilized mixture was subsequently resuspended with an aqueous solution of radioactive .sup.99m Tc, and upon incubation, in less than about 5 minutes, greater than 95% incorporation of .sup.99m Tc by the conjugate was observed. Part PAR_50: Radiopurity of the radiolabelled Fab' fragments was determined by Instant Thin Layer Chromatography (ITLC-SG, Gelman, Ann Arbor, Mich.). Saline, methylethylketone and IAW (isopropanol:ammonia:water 2:1:5) were used for mobile phases to determine percent incorporation, free pertechnetate levels and colloid, respectively. ITLC strips were garciamartha@example.org =0.5. Part PAR_51: Results of .sup.99m Tc incorporation are presented in FIG. 3. As shown in FIG. 3, when an aqueous solution of .sup.99m TCO.sub.4 was combined with the lyophilized mixture, &gt;95% Tc was incorporated into the conjugate in less than 5 minutes. Part PAR_52: In contrast, the two pot method of the prior art, i.e., EP 0569132 A1, (where the chemical reducing agent and lyoprotectant-transchelator are lyophilized together, then combined with radiolabel and subsequently added to a liquid formulation of the conjugate), required over 75 minutes to incorporate &gt;95% Tc, at loadings of 50-200 mCi Tc per 1 mg conjugate, which is typical of clinical situations. Additionally, the resultant radioconjugate prepared according to this prior art reference might need to be filtered to remove any aggregate particles formed, prior to administration. Part PAR_53: Moreover, as seen in FIG. 3, using the present invention, good speed and efficiency of labeling was obtained even with increasing levels of radiolabel, in the range of 50-200 mCi/mg immuno-conjugate. Part PAR_54: However, EP 0 569 132 A1 discloses that using the two pot tricine labeling method, &gt;90% Tc is incorporated in less than 5 minutes, contradicting the present inventors' results using this method. In contradistinction to the results obtained using the present invention, these two-pot experiments showing rapid labeling were performed with .sup.99m Tc at a specific activity of only 3 mCi/mg conjugate, far less than what is clinically required, which preferably is 50-200 mCi/mg conjugate. Furthermore, at greater specific activities (140 mCi/mg), 95% incorporation was reported after a 75-90 minute incubation. Thus, it is an important advantage of the present invention that high specific activity (50-200 mCi/mg) radiolabeling can be achieved in less than 5 minutes. Part PAL_9: 6.2.2 Long Term Stability of Lyophilized Mixture Part PAR_55: The lyophilized mixture of tricine, tin, and conjugate prepared as described in Section 6.2 was garciamartha@example.org. C. or 25.degree. C. for extended periods of time and still retained activity. As shown in Table I the same formulation of conjugate, either as a lyophilized mixture with transchelator and tin dichloride dihydrate or as an aqueous mixture, was garciamartha@example.org. C. or 25.degree. C. for up to 14 months. The differentially stored formulations were subsequently tested for efficiency of radiolabeling by measuring percent incorporation of radiolabel into the conjugate, percent pertechnetate, percent radiolabelled transchelator, and percent colloid formation. These results are presented in Table I and in FIG. 4. Part TBL: TABLE I ______________________________________ TIME % INCP.sup.1 % TcO.sub.4 % Tc-Tricine % COLLOID ______________________________________ LIQUID garciamartha@example.org. C. Initial 96.21 .+-. 0.31 1.10 .+-. 0.74 2.69 .+-. 1.05 Not Done 1 Week 96.86 .+-. 0.27 1.33 .+-. 0.16 1.81 9.13 .+-. 8.80 8 Weeks 87.77 .+-. 0.15 0.76 .+-. 0.18 11.48 .+-. 0.19 2.38 .+-. 0.23 3 No. 87.56 .+-. 0.30 0.59 .+-. 0.01 11.85 .+-. 0.32 4.66 .+-. 0.80 5 Mo. 81.96 .+-. 0.63 0.44 .+-. 0.18 17.60 .+-. 0.45 3.02 .+-. 1.05 14 Mo. 70.57 .+-. 0.69 0.19 .+-. 0.05 29.20 .+-. 0.08 0.60 .+-. 0.14 LIQUID garciamartha@example.org. C. Initial 96.21 .+-. 0.31 1.10 .+-. 0.74 2.69 .+-. 1.05 Not Done 1 Week 94.72 .+-. 0.16 2.05 .+-. 0.24 3.23 1.43 .+-. 0.04 8 Weeks 64.21 .+-. 1.08 0.97 .+-. 0.04 34.82 .+-. 0.41 2.61 .+-. 0.16 3 Mo. 55.93 .+-. 0.11 1.13 .+-. 0.06 42.94 .+-. 0.05 2.42 .+-. 0.71 5 Mo. 53.72 .+-. 0.34 2.30 .+-. 1.34 43.98 .+-. 1.68 7.80 .+-. 8.30 14 Mo. Not Done Not Done Not Done Not Done LYOPHILIZED garciamartha@example.org. C. Initial 98.66 .+-. 0.11 1.53 .+-. 0.37 0.82 .+-. 0.49 8.32 .+-. 1.46 1 Week 98.22 .+-. 0.01 0.30 .+-. 0.08 1.49 .+-. 0.08 2.29 .+-. 0.10 8 Weeks 98.71 .+-. 0.23 0.37 .+-. 0.17 0.92 .+-. 0.39 5.12 .+-. 0.58 5 Mo. 98.03 .+-. 0.27 0.37 .+-. 0.22 1.61 .+-. 0.05 2.58 .+-. 0.56 14 Mo. 98.00 .+-. 0.16 0.03 .+-. 0.07 1.97 .+-. 0.02 1.57 .+-. 0.11 LYOPHILIZED garciamartha@example.org. C. Initial 98.66 .+-. 0.11 0.53 .+-. 0.37 0.82 .+-. 0.49 8.32 .+-. 1.46 1 Week 98.31 .+-. 0.18 0.23 .+-. 0.05 1.47 .+-. 0.13 4.99 .+-. 1.63 8 Weeks 98.58 .+-. 0.15 0.21 .+-. 0.04 1.22 .+-. 0.10 5.14 .+-. 1.53 5 Mo. 98.37 .+-. 0.10 0.23 .+-. 0.04 1.40 .+-. 0.08 2.77 .+-. 1.63 14 Mo. 97.21 .+-. 0.41 0.02 .+-. 0.04 Not Done 1.76 .+-. 0.40 ______________________________________ .sup.1 Percent incorporation into the conjugate. Part PAR_56: Table I demonstrates the long term stability of the lyophilized mixture of tricine, tin dichloride dihydrate, and conjugate stored at either room temperature garciamartha@example.org. C. as compared to liquid formulations stored at room temperature or 2-8.degree. C. Methods for testing .sup.99m Tc incorporation, percent pertechnetate, percent labeled transchelator, and percent colloid formation herein are as described by Robbins, 1984, Chromatography of Technetium-99.sup.m Radiopharmaceuticals: A Practical Guide., Society of Nuclear Medicine, NY, N.Y. Part PAR_57: As demonstrated in Table I and FIG. 4 over a 14 month period, the liquid formulations have shown a continuous decline in activity even when garciamartha@example.org. C. (by 8 weeks the percent incorporation fell below the required specification (90%) of the conjugate for use in vivo). In contrast, the formulations prepared using the present one pot lyophilization method have shown excellent stability. Part PAR_58: The lyophilized formulation according to the present invention, after 14 garciamartha@example.org. C. still shows excellent stability by every parameter measured: HPLC and SDS-PAGE, immunoreactivity, protein concentration, Isoelectric focusing (IEF), hydrolysis product formation and linker labeling functional group quantitation. The protocols for measuring these parameter are well known in the art or are as follows. For example, 15A8 immunoreactivity was determined by a radioimmunoassay using live ME180 cells. Trypsinized ME180 cells were washed and serially diluted to 2.times.10.sup.6 cells/mL in MEM containing 10 mM HEPES and 10% fetal bovine serum (MEM-FBS). To each cell dilution was added 1.times.10.sup.5 cpm of .sup.99m Tc-labeled 15A8. The cells were incubated for 1 garciamartha@example.org. C. and were collected by centrifugation, washed and counts obtained in a gamma counter. The immunoreactive fraction was determined by plotting the inverse of the bound fraction versus the inverse of the cell concentration. The Y intercept, the fraction of radioactivity at infinite antigen excess, was determined by linear regression analysis. Part PAR_59: Table II shows a comparison of the lyophilized formulation of conjugate, transchelator, and chemical reducing agent, (CYT-402, tricine, and tin dichloride dihydrate), or as an aqueous conjugate preparation, garciamartha@example.org. C. or 25.degree. C. These formulations were tested at the various time points for the various parameters listed after labeling with .sup.99m Tc. TBL3 TABLE II - CYT-402 INSTANT KIT WITH TRICINE AND TIN LYOPHILIZED LIQUID garciamartha@example.org. C. INITIAL* T = 1 WEEK T = 8 WEEKS T = 3 MONTHS T = 5 MONTHS T = 14 MONTHS ASSAY BAHNH-ALC MOLE ND ND ND ND 0.07 .+-. 0.02 0.24 .+-. 0.04 RATIO MONOMER % ND 100 .+-. 0.00 94.81 .+-. 0.65 95.43 .+-. 0.43 96.38 .+-. 43 93.33 .+-. 1.86 SDS-PAGE BANDS 2 MAJOR @ 25000D 2 MAJOR @ 25000D 2 MAJOR @ 25000D 2 MAJOR @ 25000D 2 MAJOR @ 25000D 2 MAJOR @ 25000D 1 MINOR @ 50000D 1 MINOR @ 50000D 1 MINOR @ 50000D 1 MINOR @ 50000D 1 MINOR @ 50000D 1 MINOR @ 50000D IEF PI ND 2 MAJOR BANDS 2 MAJOR BANDS 2 MAJOR BANDS 2 MAJOR, 2 MAJOR, pI 7.0, 6.4 pI 7.0, 6.4 pI 7.0, 6.4 1 MINOR BAND 1 MINOR BAND pI 7.0, 6.4, 6.3 PROTEIN mg/mL 2.3 .+-. 0.10 1.75 .+-. 0.24 2.26 .+-. 0.04 1.80 .+-. 0.10 1.89 .+-. 0.11 1.73 .+-. 0.05 (IN CUVETTE) .mu.M/L 4.620 3.50 .+-. 0.48 4.66 .+-. 0.28 3.60 .+-. 0.21 3.78 .+-. 0.23 3.46 .+-. 0.09 PROTEIN HYDRAZINE .mu.M/L 11.472 .+-. 0.37 11.23 .+-. 0.03 10.08 .+-. 0.43 9.91 .+-. 0.08 8.57 .+-. 0.21 6.72 .+-. 0.21 MSR 2.483 .+-. 0.081 3.24 .+-. 0.44 2.17 .+-. 0.04 2.76 .+-. 0.18 2.27 .+-. 0.19 1.94 .+-. 0.01 pH ND 5.09 .+-. 0.05 5.05 .+-. 0.01 4.99 .+-. 0.01 5.06 .+-. 0.01 ND RADIOLABELING % INCP 96.21 .+-. 1.89% 96.86 .+-. 0.28 87.77 .+-. 0.15 87.56 .+-. 0.30 81.96 .+-. 0.63 70.57 .+-. 0.69 IMMUNORX % 81.3% 70.9% 79.6% ND ND ND STD % 88.5% 77.2% 79.6% ND ND ND % OF 91.9% 91.8% 100.00 ND ND ND STD LIQUID garciamartha@example.org. C. T = 1 WEEK T = 8 WEEKS T = 3 MONTHS T = 5 MONTHS ASSAY BAHNH-ALC MOLE ND ND ND &lt;0.05 RATIO MONOMER % 100 .+-. 0.00 86.69 .+-. 4.38 88.95 .878-275-7613 .+-. 0.65 SDS-PAGE BANDS 2 MAJOR @ 25000D 2 MAJOR @ 25000D 2 MAJOR @ 25000D 2 MAJOR @ 25000D 1 MINOR @ 50000D 1 MINOR @ 50000D 1 MINOR @ 50000D 1 MINOR @ 50000D IEF PI 2 MAJOR BANDS 3 MAJOR BANDS 3 MAJOR BANDS 3 MAJ/4 MIN BANDS pI 7.0, 6.4 pI 7.0, 6.4, 6.2 pI 7.0, 6.4, 6.2 pI 7.0, 6.4, 6.2 PROTEIN mg/mL 1.85 .+-. 0.02 2.15 .+-. 0.01 1.70 .+-. 0.04 1.73 .+-. 0.07 (IN CUVETTE) .mu.M/L 3.70 .+-. 0.03 4.34 .+-. 0.03 3.41 .+-. 0.08 3.46 .+-. 0.14 PROTEIN HYDRAZINE .mu.M/L 10.55 .+-. 0.08 5.64 .+-. 1.36 4.00 .+-. 1.71 2.80 .+-. 0.53 MSR 2.85 .+-. 0.00 1.30 .+-. 0.32 1.18 .+-. 0.53 0.81 .+-. 0.19 pH 5.10 .+-. 0.01 5.01 .+-. 0.06 4.99 .+-. 0.00 5.11 .+-. 0.02 RADIOLABELING % INCP 94.72 .+-. 0.16 64.21 .+-. 1.08 55.93 .+-. 0.11 53.72 .+-. 0.34 IMMUNORX % 70.4% 76.4 .+-. 0.4% ND ND STD % 77.2% 79.6% ND ND % OF 91.2% 96.0 .+-. 0.5% ND ND STD LYOPHILIZED garciamartha@example.org. C. INITIAL* T = 1 WEEK T = 8 WEEKS T = 5 MONTHS T = 14 MONTHS ASSAY BAHNH-ALC MOLE ND ND ND NONE DETECTED NONE DETECTED RATIO MONOMER % 97.45 .+-. 0.34% 100.00 .+-. 0.00 97.16 .+-. 0.18 97.63 .+-. 0.02 99.17 .+-. 1.18 SDS-PAGE BANDS 2 MAJOR @ 25000D 2 MAJOR @ 25000D 2 MAJOR @ 25000D 2 MAJOR @ 25000D 2 MAJOR @ 25000D 1 MINOR @ 50000D 1 MINOR @ 50000D 1 MINOR @ 50000D 1 MINOR @ 50000D 1 MINOR @ 50000D IEF PI ND 3 MAJOR BANDS 3 MAJOR BANDS 3 MAJOR BANDS 3 MAJOR BANDS pI 7.0, 6.4, 6.2 pI 7.0, 6.4, 6.2 pI 7.0, 6.4, 6.2 PROTEIN mg/ 1.09 .+-. 0.07 0.87 .+-. 0.09 0.95 .+-. 0.06 0.95 .+-. 0.05 0.81 .+-. 0.03 VIAL (IN CUVETTE) .mu.M/L 4.350 3.50 .+-. 0.35 3.79 .+-. 0.23 3.80 .+-. 0.21 3.23 .+-. 0.13 PROTEIN HYDRAZINE .mu.M/L 10.057 .+-. 0.29 8.99 .+-. 0.59 7.68 .+-. 0.72 8.34 .+-. 1.33 8.64 .+-. 0.75 MSR 2.312 .+-. 0.067 2.57 .+-. 0.09 2.02 .+-. 0.07 2.19 .+-. 0.23 2.68 .+-. 0.13 pH 4.91 .+-. 0.01 4.94 .+-. 0.00 4.92 .+-. 0.01 5.02 .+-. 0.00 RADIOLABELING % INCP 98.66 .+-. 0.10% 98.22 .+-. 0.01 98.71 .+-. 0.23 98.03 .+-. 0.27 98.00 .+-. 0.16 IMMUNORX % 80.6% 79.7% 85.2% 77.7% ND STD % 88.5% 77.2% 79.6% ND ND % OF 91.1% 103.2% 107.1% ND ND STD LYOPHILIZED garciamartha@example.org. C. T = 1 WEEK T = 8 WEEKS T = 5 MONTHS T = 14 MONTHS ASSAY BAHNH-ALC MOLE ND ND NONE DETECTED NONE DETECTED RATIO MONOMER % 100 .+-. 0.00 97.09 .+-. 0.13 98.09 .+-. 0.06 97.94 .+-. 0.37 SDS-PAGE BANDS 2 MAJOR @ 25000D 2 MAJOR @ 25000D 2 MAJOR @ 25000D 2 MAJOR @ 25000D 1 MINOR @ 50000D 1 MINOR @ 50000D 1 MINOR @ 50000D 1 MINOR @ 50000D IEF PI 3 MAJOR BANDS 3 MAJOR BANDS 3 MAJOR BANDS 3 MAJOR BANDS pI 7.0, 6.4, 6.2 pI 7.0, 6.4, 6.2 pI 7.0, 6.4, 6.2 PROTEIN mg/ 0.94 .+-. 0.09 1.02 .+-. 0.05 0.92 .+-. 0.03 0.79 .+-. 0.01 VIAL (IN CUVETTE) .mu.M/L 3.75 .+-. 0.14 4.04 .+-. 0.22 3.70 .+-. 0.14 3.16 .+-. 0.06 PROTEIN HYDRAZINE .mu.M/L 8.78 .+-. 0.13 7.40 .+-. 0.05 8.89 .+-. 0.35 7.55 .+-. 0.05 MSR 2.59 .+-. 0.06 1.83 .+-. 0.08 2.40 .+-. 0.00 2.39 .+-. 0.02 pH 4.93 .+-. 0.01 4.93 .+-. 0.00 5.04 .+-. 0.00 ND RADIOLABELING % INCP 98.31 .+-. 0.18 98.58 .+-. 0.15 98.37 .+-. 0.10 97.21 .+-. 0.41 IMMUNORX % 60.9% 98.4% 72.7% ND STD % 77.2% 79.6% ND ND % OF 78.9% 123.6% ND ND STD ND = NOT DONE *This material was prepared, placed in a vial and lyophilized. The lyophilized vials were garciamartha@example.org. C. for 4 weeks until this study was initiated. Part PAL_10: 6.2.3 Stannous Stability Part PAR_60: In an additional experiment, radiolabeling characteristics of formulations containing varying amounts of stannous dichloride dihydrate versus varying amounts of immunoconjugate were studied. Results are presented in Table III. When no immunoconjugate was included in the lyophilized tricine/tin formulation, more tin was required (100 .mu.g) to achieve even minimal .sup.99m Tc incorporation (41%). When 0.2 mg of immunoconjugate was lyophilized with tricine and tin, the highest concentration of tin studied (100 .mu.g) resulted in 84% incorporation. However, surprisingly when 0.5 mg of immunoconjugate was lyophilized with tricine and tin, even the lowest concentration of tin studied (25 .mu.g) resulted in 90% incorporation. It appeared that increasing concentrations of immunoconjugate helped to stabilize the stannous ion in the lyophilized formulation for effective reduction of technetium and subsequent high incorporation into an immunoconjugate. Part TBL_2: TABLE III ______________________________________ SUMMARY OF RADIOLABELING DATA ON CYT-402 LYOPHILIZED PROTEIN/TIN MATRIX STUDY % TIN % INCP % TcO.sub.4 % Tc-Tricine COLLOID ______________________________________ TRICINE (36 MG) LYOPHILIZED WITH TIN AND 0 mg CYT-402* 25 .mu.g 3.35 .+-. 0.26 88.33 .+-. 0.14 8.32 .+-. 0.40 0.04 .+-. 0.02 50 .mu.g 3.44 .+-. 0.43 87.59 .+-. 0.86 8.98 .+-. 0.43 0.52 .+-. 0.24 100 .mu.g 41.00 .+-. 20.23 37.20 .+-. 17.12 21.81 .+-. 3.10 1.87 .+-. 1.03 TRICINE (36 MG) LYOPHILIZED WITH TIN AND 0.2 mg CYT-402 25 .mu.g 38.66 .+-. 19.24 42.06 .+-. 7.11 19.29 .+-. 12.13 2.69 .+-. 1.22 50 .mu.g 52.25 .+-. 0.00 28.05 .+-. 12.08 19.71 .+-. 12.09 4.18 .+-. 0.48 100 .mu.g 84.29 .+-. 2.51 1.73 .+-. 0.43 13.98 .+-. 2.94 5.66 .+-. 0.42 TRICINE (36 MG) LYOPHILIZED WITH TIN AND 0.5 mg CYT-402 25 .mu.g 90.62 .+-. 0.05 2.61 .+-. 0.19 6.78 .+-. 0.23 8.39 .+-. 3.04 50 .mu.g 86.18 .+-. 5.26 2.95 .+-. 2.42 10.87 .+-. 2.84 8.06 .+-. 2.79 100 .mu.g 89.98 .+-. 1.84 0.76 .+-. 0.46 9.27 .+-. 2.30 8.00 .+-. 1.63 ______________________________________ *The 0 mg CYT402 vials were incubated with .sup.99m TC for 15 minutes, then CYT402 liquid formulation was added for a final specific activity of 50 mCi/mg. Part PAL_11: 6.2.4 Non-Toxicity of Tricine Part PAR_61: Tricine was tested to determine its toxicity in mice and therefore suitability as a component of a pharmaceutical composition. 10 mice were injected i.v. with a single dose of 2.34 mg/kg body weight of tricine in saline solution. This dose represents 4.5 times, assuming a 70 kg human, of an amount of tricine used in a commercial embodiment of the invention. One mouse died for unknown reasons less than one day after receiving the injection. The remaining 9 mice survived until dissection, which was 7 days for 4 mice and 14 days for the remaining 5 mice. The body weights of the test subjects rose slowly during the study at a rate similar to control, non-injected mice. Furthermore, the weights of the spleen, liver, and kidneys were unchanged from 7 to 14 days, and were similar to that of the controls. There were no signs of toxicity in the internal organs or in the activity or appearance of the mice. Thus, in this study tricine appeared to have no toxic side effects in mice, even when administered at a dose 4.5 times the clinical dose. Part PAL_12: 6.2.5 In Vivo Clearance Rates: Comparison Between a Liquid Formulation and a Formulation Prepared Using the Present Lyophilized Kit Part PAR_62: A side by side comparison of in vivo clearance rates between two formulations of a .sup.99m Tc-labeled conjugate, CYT-402 (mAb 15A8 Fab'-BAHNH), was done. The radioconjugates were prepared using two different ways, the two pot method of the prior art and the one pot method of the present invention. In both protocols the same transchelator, reducing agent and conjugate were used and in the same amounts. In each case, 36 mg of tricine, 50 .mu.g of stannous dichloride dihydrate, and 1 mg CYT-402 were used. Part PAR_63: In the two pot method, the .sup.99m Tc was first combined with the reducing agent and transchelator. Next, this mixture was combined with the conjugate molecule, in a liquid formulation. Part PAR_64: In the one pot method of the present invention the reducing agent, the transchelator, and the conjugate were mixed together and lyophilized. This lyophilized mixture was then mixed with an aqueous solution of .sup.99m Tc. Part PAR_65: After the addition of the .sup.99m Tc to the conjugates, the solutions were incubated such that &gt;90% of the .sup.99m Tc was incorporated into the conjugate molecules. The biodistribution characteristics of the resultant radioconjugates prepared by the two methods were compared. Athymic (nu/nu) Swiss background nude mice (Taconic Farms, Germantown, N.Y.) bearing MCF-7 (American Type Culture Collection, Rockville Md.) xenographs were used to determine the biodistribution, pharmacokinetics and tumor imaging of the conjugates. Mice were injected i.v. with 20 .mu.g of Fab' fragments containing 0.5-1 mCi .sup.99m Tc. Mice were dose calibrated and bled for initial blood and whole body pharmacokinetics immediately after injection of the .sup.99m Tc-Fab' fragments. Blood pharmacokinetics and whole body clearances were determined by bleeding or dose calibrating the mice at 2,4,6, and 24 hours post-injection. Dissected tissues were weighted and the amount of .sup.99m Tc determined by gamma counting. Data were represented as the ratio of the cpm/g in each organ compared to the cpm/g in blood (organ/blood ratio) and the percentage dose injected (ID) per gram in each organ. The biological half-life (whole body) of Tc was calculated assuming a single experimental decay function from mice dose calibration data. Similarly, the blood half-life was calculated from the average percentage ID/g in blood at 2, 4, 6, and 24 hours. Part PAR_66: The results of this comparison are shown in FIGS. 5a and 5b and FIGS. 6a-d. Part PAR_67: As seen in FIG. 5a, there was no discernable difference in the rate of whole body clearance between the two separately prepared radioconjugates in tumor bearing mice or normal mice. FIG. 5b shows similar results for blood clearance. Part PAR_68: Additionally, FIGS. 6a-d show that there were no significant differences in the organ distribution between the two formulations. Part PAR_69: These results suggest that there is no difference in the in vivo behavior of the two differently prepared radioconjugates in whole body/blood clearance and that the specificity of the radioconjugate produced by the one pot method of the present invention appeared unchanged in comparison to the two pot method. Part PAC_6: 6.3 .sup.99m Tc Labeling of CYT-421 Part PAR_70: The labeling of immunoconjugate CYT-421, mAb B72.3-linker BL14 (BL14 is described in Section
{'bibliographic_information': "{'Patent Number': '059422106', 'Series Code': '8', 'Application Number': '339865&', 'Application Type': '1', 'Art unit': '121', 'Application Filing Date': '19941115', 'Title of Invention': 'Methods for lyoprotecting a macromolecule using tricine', 'Issue Date': '19990824', 'Number of Claims': '8', 'Exemplary Claim Number(s)': '1', 'Assistant Examiner': 'Hartley; Michael G.', 'Primary Examiner': 'Hollinden; Gary E.', 'Number of Drawing Sheets': '11', 'Number of figures': '10'}", 'source_file': './grant/1999/pftaps19990824_wk34.txt', 'source_data': 'USPTO-Grant'}