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Antibody Radiolabeling

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Part of the book series: Biotechnology: Pharmaceutical Aspects ((PHARMASP,volume XI))

Abstract

The concept of using radiolabeled antibodies in vivo dates back to 1949 when Pressman (1949) demonstrated that radiolabeled antibodies could be used to localize specific tissue. Using 131I radiolabeled anti-carcinoembryonic antigen antibodies, Goldenberg et al. (1978) imaged human colonic carcinoma xenografts and in doing so, set in motion the field of radiolabeled antibodies for use in imaging and therapy.

Antibody based imaging entails either an antibody, bivalent fragment F(ab′)2, monovalent fragment Fab′ or antibody construct (minibody, diabody, tribody, etc.), with either a gamma or positron emitting radioisotope, having an appropriate energy, and an external camera system. A list of radioisotopes suitable for imaging is shown in Table 19-1.

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References

  • Axworthy DB, Reno JM, Hylarides MD, Mallett RW, Theodore LJ, Gustavson LM, Su F, Hobson LJ, Beaumier PL, Fritzberg AR (2000) Cure of human carcinoma xenografts by a single dose of pretargeted yttrium 90 with negligible toxicity. Proc Natl Acad Sci U S A 97:1802–1807

    Article  PubMed  CAS  Google Scholar 

  • Bolton AE, Hunter WM (1973) The labeling of proteins to high specific radioactivity by conjugation to a 125I- containing acylating agent. Biochem J 133:529–538

    PubMed  CAS  Google Scholar 

  • Broan CJ, Cox JPL, Craig AS, Kataky R, Parker D, Harrison A, Randall AM, Ferguson G (1991) J Chem Soc Perkin Trans 2:87–99

    Google Scholar 

  • Buchanan L, Jurek P, Redshaw R (2007) Nuclear imaging drug development tools. GEN 27:23–25

    Google Scholar 

  • Camera L, Kinuya S, Garmestani K, Wu C, Briechbiel MW, Pai LH, McMurry TJ, Gansow OA, Pastan I, Paik CH et al (1994) Evaluation of the serum stability and in vivo biodistribution of CHX-DTPA and other ligands for yttrium labeling of monoclonal antibodies. J Nucl Med 35:882–889

    PubMed  CAS  Google Scholar 

  • Casadevall A, Goldstein H, Dadachova E (2007) Targeting host cells harbouring viruses with radiolabeled antibodies. Expert Opin Biol Ther 7:595–597

    Article  PubMed  CAS  Google Scholar 

  • Chappell LL, Ma D, Milenic DE, Garmestani K, Venditto V, Beitzel MP, Brechbiel MW (2003) Synthesis and evaluation of novel bifunctional chelating agents based on 1, 4, 7, 10-tetraazacyclododecane-N, N′, N″, N″′-tetraacetic acid for radiolabeling proteins. Nucl Med Biol 30:581–595

    Article  PubMed  CAS  Google Scholar 

  • Cornelissen B, Hu M, McLarty K, Costantini D, Reilly RM (2007) Cellular penetration and nuclear importation properties of 111In-labelled and 123I-labeled HIV-1 Tat peptide immunocojugates in BT-474 human breast cancer cells. Nucl Med Biol 34:37–46

    Article  PubMed  CAS  Google Scholar 

  • Dadachova, E. and Casadevall, A. (2005) Antibodies as delivery vehicles for radioimmunotherapy of infectious disease. Expert Opin. Drug Delivery 2(6):1075–1084

    Google Scholar 

  • Dadachova E, Casadevall A (2006) Treatment of infection with radiolabeled antibodies. Q J Nucl Med Mol Imaging 50:193–204

    PubMed  CAS  Google Scholar 

  • Dadachova E, Patel MC, Toussi S, Apostolidis C, Morgenstern A, Brechbiel MW, Gorny MK, Zolla-Pazner S, Casadevall A, Goldenstein H (2006) Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins. PLoS Med 3:2094–2103

    Article  CAS  Google Scholar 

  • Doran DM, Spar IL (1980) Oxidative iodine monochloride iodination technique. J Immunol Methods 39:155–163

    Article  PubMed  CAS  Google Scholar 

  • Fichna J, Janecka A (2003) Synthesis of target-specific radiolabeled peptides for diagnostic imaging. Bioconjug Chem 14:3–17

    Article  PubMed  CAS  Google Scholar 

  • Fraser PJ, Speck JC (1978) Protein and cell membrane iodinations with a sparingly soluble chloramide, 1, 3, 4, 6-tetrachloro-3a, 6a-diphenylglycoluril. Biochem Biophys Res Commun 80:849–857

    Article  Google Scholar 

  • Fritzberg AR, Berninger RW, Hadley SW, Wester DW (1988) Approaches to radiolabeling of antibodies for diagnosis and therapy of cancer. Pharm Res 5:325–334

    Article  PubMed  CAS  Google Scholar 

  • Fritzberg AR, Kasina S, Rao TN, VanderHeyden JL, Srinivasan A (1992) Metal-radionuclide-labeled proteins and glycoproteins for diagnosis and therapy. US Patent 5,091,514

    Google Scholar 

  • Gansow OA, Brechbiel MW (1989) Backbone polysubstituted chelate for forming a metal chelate protein conjugate. US Patent 4831175

    Google Scholar 

  • Gansow OA, Brechbiel MW (1992) Bifunctional DTPA-type ligand. US Patent 05124471

    Google Scholar 

  • Garg PK, Archer GE, Bigner DD, Zalutsky MR (1989) Synthesis of radioiodinated n-succinimidyl iodobenzoate: optimization for use in antibody labeling. Appl Radiat Isot 40:485–490

    Article  CAS  Google Scholar 

  • Garg PK, Garg S, Zalutsky MR (1993) N-Succinimidyl 4-methyl-3-(tri-n-butylstannyl)benzoate: synthesis and potential utility for the radioiodination of monoclonal antibodies. Nucl Med Biol 20:379–387

    Article  PubMed  CAS  Google Scholar 

  • Garrison WM (1987) Reaction mechanisms in the radiolysis of peptides, polypeptides and proteins. Chem Rev 87:381–398

    Article  CAS  Google Scholar 

  • Goldenberg DM (2002) Targeted therapy of cancer with radiolabeled antibodies. J Nucl Med 43:693–713

    PubMed  CAS  Google Scholar 

  • Goldenberg DM, Sharkey RM (2006) Advances in cancer therapy with radiolabeled monoclonal antibodies. Q J Nucl Med Mol Imaging 50:248–264

    PubMed  CAS  Google Scholar 

  • Goldenberg DM, DeLand F, Kim E, Bennett S, Primus FJ, van Nagell JR, Estes N, DeSimone P, Rayburn P (1978) Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning. N Engl J Med 298:1384–1386

    Article  PubMed  CAS  Google Scholar 

  • He J, Liu G, Dou S, Gupta S, Rusckowski M, Hnatowich D (2007) An improved method for covalently conjugating morpholino oligomers to antitumor antibodies. Bioconjug Chem 18:983–988

    Article  PubMed  CAS  Google Scholar 

  • Helmkamp RW, Contreras MA, Bale WF (1967) I-131 labeling of protein by iodine monochloride. Int J Appl Radiat Isot 18:737–746

    Article  PubMed  CAS  Google Scholar 

  • Hnatowich DJ, Mardirossian G, Ruskowski M, Fogarasi M, Virzi F, Winnard P Jr (1993) Directly and indirectly technicium-99m-labeled antibodies-A comparison of in vitro and animal in vivo properties. J Nucl Med 34:109–119

    PubMed  CAS  Google Scholar 

  • Hnatowich DJ, Qu T, Chang F, Ley AC, Ladner RC, Rusckowsky M (1998) Labeling peptides with technitium-99m using a bifunctional chelator of a N-hydroxysuccinimde ester of mercaptoacetyltriglycine. J Nucl Med 39:56–64

    PubMed  CAS  Google Scholar 

  • Hu M, Chen P, Chan C, Scollard DA, Reilly RM (2006) Site-specific conjugation of HIV-1 Tat peptides to IgG: a potential route to construct radioimmunoconjugates for targeting intracellular and nuclear epitopes in cancer. Eur J Nucl Med Mol Imaging 33:301–310

    Article  PubMed  CAS  Google Scholar 

  • Hubin TJ, Meade TJ (2002) Novel macrocyclics magnetic resonance imaging contrast agents. International Patent WO 02/006287.A2

    Google Scholar 

  • Hunter WM, Greenwood FC (1962) Preparation of iodine-131 labeled human growth hormone of high specific activity. Nature 194:495–496

    Article  PubMed  CAS  Google Scholar 

  • Jurcic JG (2005) Immunotherapy for acute myeloid leukemia. Curr Oncol Rep 7:339–346

    Article  PubMed  CAS  Google Scholar 

  • Kaminski MS, Estes J, Zasadny KR, Francis IR, Ross CW, Tuck M, Regan D, Fisher S, Gutierrez J, Kroll S, Stagg R, Tidmarsh G, Wahl RL (2000) Radioimmunotherapy with 131I tositumomab for relapsed refractory B-cell non-hodgkin lymphoma: updated results and long term follow-up of the University of Michigan Experience. Blood 96:1259–1266

    PubMed  CAS  Google Scholar 

  • Lee J, Garmestani K, Wu C, Brechbiel MW, Chang HK, Choi CW, Gansow OA, Carrasquillo JA, Paik CH (1997) In vitro and in vivo evaluation of structure–stability relationship of 111In and 67Ga-labeled antibodies via 1B4M and C-NOTA chelates. Nucl Med Biol 24:225–230

    Article  PubMed  CAS  Google Scholar 

  • Lidmo T, Boven E, Cuttitta F, Fedorko J, Bunn PA (1984) Determination of the immunoreactive fraction of radiolabeled monoclonal antibodies of radiolabeled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess. J Immunol Methods 72:77–89

    Article  Google Scholar 

  • Lin Y, Pagel JM, Axworthy D, Pantelias A, Hedin N, Press OW (2006) A genetically engineered anti-cd45 single-chain antibody–streptavidin fusion protein for pretargeted radioimmunotherapy of hematologic malignancies. Cancer Res 66:3884–3892

    Article  PubMed  CAS  Google Scholar 

  • Liu S, Edwards DS (2001a) Bifunctional chelators for therapeutic lanthanide radiopharmaceuticals. Bioconjug Chem 12:7–34

    Article  PubMed  Google Scholar 

  • Liu S, Edwards DS (2001b) Stabilization of 90Y-labled DOTA-biomolecule conjugates using gentisic acid and ascorbic acid. Bioconjug Chem 12:554–558

    Article  PubMed  CAS  Google Scholar 

  • Liu G, Mang’era K, Liu N, Gupta S, Rusckowski M, Hnatowich DJ (2002) Tumor pretargeting in mice using 99mTc-labeled morpholino, a DNA analog. J Nucl Med 43:384–391

    PubMed  CAS  Google Scholar 

  • Liu S, Ellars CE, Edwards DS (2003) Ascorbic acid: useful as a buffer agent and radiolytic stabilizer for metalloradiopharmaceuticals. Bioconjug Chem 14:1052–1056

    Article  PubMed  CAS  Google Scholar 

  • Liu G, Dou S, Mardirossian G, He J, Zhang S, Liu X, Rusckowski M, Hnatowich D (2006) Successful radiotherapy of tumor in pretargeted mice by 188Re radiolabeled phosphorodiamidate morpholino oligomer, a synthetic DNA analogue. Clin Cancer Res 12:4958–4964

    Article  PubMed  CAS  Google Scholar 

  • Liu G, Dou S, Yin D, Squires S, Liu X, Wang Y, Rusckowski M, Hnatowich D (2007) A novel pretargeting method for measuring antibody internalization in tumor cells. Cancer Biother Radiopharm 22:33–39

    Article  PubMed  Google Scholar 

  • Luyt LG, Jenkins HA, Hunter DH (1999) An N2H2 Bifunctional chelator for technitium-99m and rhenium complexation, conjugation and epimerization to a single isomer. Bioconjug Chem 10:470–479

    Article  PubMed  CAS  Google Scholar 

  • Marchalonis JJ (1969) An enzymatic method for the trace iodination of immunoglobulins and other proteins. Biochem J 113:299–305

    PubMed  CAS  Google Scholar 

  • Markwell MAK (1982) A new solid state reagent to iodinate proteins. Anal Biochem 125:427–432

    Article  PubMed  CAS  Google Scholar 

  • McDevitt MR, Scheinberg DA (2002) Ac-225 and her daughters: the many faces of shiva. Cell Death Differ 9:593–594

    Article  PubMed  CAS  Google Scholar 

  • Milenic DE, Garmestani K, Chappell LL, Dadachova E, Yordanov A, Ma D, Schlom J, Brechbiel MW (2002) In vivo comparison of macrocyclic and acyclic ligands for radiolabeling of monoclonal antibodies with 177Lu for radioimmunotherapeutic applications. Nucl Med Biol 29:432–442

    Article  Google Scholar 

  • Moosmayer D, Berndorff D, Chang C-H, Sharkey RM, Rother A, Borkowski S, Rossi EA, McBride WJ, Cardillo TM, Goldenberg DM, Dinkelborg LM (2006) Bispecific antibody pretargeting of tumor neovasculature for improved systemic radiotherapy of solid tumors. Clin Cancer Res 12:5587–5595

    Article  PubMed  CAS  Google Scholar 

  • Paganelli G, Magnani P, Zito F, Villa E, Sudait F, Lopalco L, Rossetti C, Malcovati M, Chiolerio F, Seccamani E, Siccardi AG, Fazio F (1991) Three-step monoclonal antibody tumor targeting in carcinoembryonic antigen positive patients. Cancer Res 15:5960–5966

    Google Scholar 

  • Pettit WA, Delard FH, Bennett SJ, Goldenberg DM (1980) Improved protein labeling by stannous tartrate reduction of pertechnatate. J Nucl Med 21:59–62

    PubMed  CAS  Google Scholar 

  • Pressman D (1949) The zone of localization of antibodies; the in vivo disposition of anti-mouse-kidney serum and anti-mouse-plasma serum as determined by radioactive tracers. J Immunol 63:375–388

    PubMed  CAS  Google Scholar 

  • Ram S, Buchsbaum DJ (1992) Development of 3-iodophenylisothiocyanate for radioiodination of monoclonal antibodies. Appl Radiat Isot 43:1387–1391

    Article  CAS  Google Scholar 

  • Ram S, Buchsbaum DJ (1994) Radioiodination of monoclonal antibodies D612 and 17-1A with 3-iodophenylisothiocyanate and their biodistribution in tumor-bearing nude mice. Cancer 73:808–815

    Article  PubMed  CAS  Google Scholar 

  • Reilly RM (1991) Radioimmunotherapy of malignancies. Clin Pharm 10:359–375

    PubMed  CAS  Google Scholar 

  • Reilly RM (2006) Radioimmunotherapy of solid tumors: the promise of pretargeting strategies using bispecific antibodies and radiolabelled haptens. J Nucl Med 47:196–199

    PubMed  CAS  Google Scholar 

  • Rennen HJ, Boerman OC, Koendens EB, Oyen WJ, Corsten FH (2000) Labeling proteins with Tc-99m via hydrazinonicotinamide (HYNIC). Optimization of the comjugation reaction. Nucl Med Biol 27:599–604

    Article  PubMed  CAS  Google Scholar 

  • Rossi AR, Goldenberg DM, Cardillo TM, McBride WJ, Sharkey RM, Chang CH (2006) Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targeting. Proc Natl Acad Sci U S A 103:6841–6846

    Article  PubMed  CAS  Google Scholar 

  • Sato N, Hassan R, Axworthy DB, Wong KJ, Yu S, Theodore LJ, Lin Y, Park L, Brechbiel MW, Pastan I, Paik CH, Carrasquillo JA (2005) Pretargeted radioimmunotherapy of mesothelin-expressing cancer using a tetravalent single-chain Fv–streptavidin fusion protein. J Nucl Med 46:1201–1209

    PubMed  Google Scholar 

  • Sharkey RM, Goldenberg DM (2006) Targeted therapy of cancer: new prospects for antibodies and immunoconjugates. CA Cancer J Clin 56:226–243

    Article  PubMed  Google Scholar 

  • Sharkey RM, Cardillo TM, Rossi EA, Chang C-H, Karacay H, McBride WJ, Hansen HJ, Horak ID, Goldenberg DM (2005) Signal amplification in molecular imaging by pretargeting a multivalent bispecific antibody. Nat Med 11:1250–1255

    Article  PubMed  CAS  Google Scholar 

  • Shochat D, Chan ASK, Buckley MJ, Colcher D (1999) Radioprotectant for peptides labeled with radioisotopes. US Patent 5,961,955

    Google Scholar 

  • Smith SV (2004) Molecular imaging with copper-64. J Inorg Biochem 98:1874–1901

    Article  PubMed  CAS  Google Scholar 

  • Smith-Jones PM, Stolz B, Bruns C, Albert R, Reist HW, Fridrich R, Maecke HR (1994) Galliuim-67/Galluim-68-[DFO]-Octreotide – a potential radiopharmaceutical for PET imaging of somatostatin receptor-positive tumors: synthesis and radiolabeling in-vitro and preliminary in-vivo studies. J Nucl Med 35:317–325

    PubMed  CAS  Google Scholar 

  • Stimmel JB, Kull FC Jr (1998) Samarium-153 and Lutetium-177 chelation properties of selected macrocyclic and acyclic ligands. Nucl Med Biol 25:117–125

    Article  PubMed  CAS  Google Scholar 

  • Stimmel JB, Stockstill ME, Kull FC Jr (1995) Yttrium-90 chelation properties of tetraazatetraacetic acid macrocycles, diethyltriaminepentaacetic acid analogues and a novel terpyridine acyclic chelator. Bioconjug Chem 6:219–225

    Article  PubMed  CAS  Google Scholar 

  • Supiot S, Faivre-Chauvet A, Couturier O, Heymann MF, Robillard N, Kraber-Bodéré F, Morandeau L, Mahé MA, Chérel M (2002) Comparison of the biological effects of MA5 and B-B4 monoclonal antibody labeled with Iodine-131 and Bismuth-213 on multiple myeloma. Cancer 94:1202–1209

    Article  PubMed  CAS  Google Scholar 

  • Vaidynathan G, Zalutsky MR (1990a) Protein radiohalogenation: observations on the design of N-succinimidyl ester acylation agents. Bioconjug Chem 1:269–273

    Article  Google Scholar 

  • Vaidynathan G, Zalutsky MR (1990b) Radioiodination of antibodies via N-succinimidyl 2, 4-dimethoxy-3-(trialkylstannyl)benzoate. Bioconjug Chem 1:387–393

    Article  Google Scholar 

  • Vaidyanathan G, Affleck D, Zalutsky MR (1993) Radioiodination of proteins using N-succinimidyl 4-hydroxy-3-iodobenzoate. Bioconjug Chem 4:78–84

    Article  PubMed  CAS  Google Scholar 

  • Volkert WA, Goeckler WF, Ehrhardt GJ, Ketring AR (1991) Therapeutic radionuclides: production and decay property considerations. J Nucl Med 32:174–185

    PubMed  CAS  Google Scholar 

  • Wilbur DS, Hadley SW, Grant LM, Hylarides MD (1991) Radioiodinated iodobenzoyl conjugates of a monoclonal antibody Fab fragment. In vivo comparisons with chloramine-T-labeled Fab. Bioconjug Chem 2:111–116

    Article  PubMed  CAS  Google Scholar 

  • Wilson DA, Garlich JR, Fordyce WA, Frank RK, Simon J, Goeckler WF, Cheng RC, Kruper WJ, McMillan K (1998) Macrocyclic tetraazacyclodecane conjugates and their use as diagnostic and therapeutic agents. US Patent 5,756,065

    Google Scholar 

  • Witzig TE, Gordon LI, Cabanillas F, Cruczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-Lopez AJ, Multani P, White CA (2002) Randomized controlled trial of yttrium-90 labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low grade follicular or transformed B-cell non-Hodgkin’s lymphoma. J Clin Oncol 20:2453–2463

    Article  PubMed  CAS  Google Scholar 

  • Wood FT, Wu NM, Gerhart JC (1975) The radioactive labeling of proteins with an iodinated amidination reagent. Anal Biochem 69:339–349

    Article  PubMed  CAS  Google Scholar 

  • Wu C, Kobayashi H, Sun B, Yoo TM, Paik CH, Gansow OA, Carrasquillo JA, Pastan I, Brechbiel MW (1997) Stereochemical influence on the stability of radio-metal complexes in vivo. Synthesis and evaluation of the four stereoisomers of 2-(p-nitrobenzyl)-trans-CyDTPA. Bioorg Med Chem 5:1925–1934

    Article  PubMed  CAS  Google Scholar 

  • Zalutsky MR, Narula AS (1987) A method for the radiohalogenation of proteins resulting in decreased thyroid uptake of radioiodine. Appl Radiat Isot 38:1051–1055

    Article  CAS  Google Scholar 

  • Zumdahl S (1997) Chemistry. Houghton Mifflin, Boston, MA, 1118 p

    Google Scholar 

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Bensimon, C., Redshaw, R. (2010). Antibody Radiolabeling. In: Shire, S., Gombotz, W., Bechtold-Peters, K., Andya, J. (eds) Current Trends in Monoclonal Antibody Development and Manufacturing. Biotechnology: Pharmaceutical Aspects, vol XI. Springer, New York, NY. https://doi.org/10.1007/978-0-387-76643-0_19

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