Development of a 124I-labeled version of the anti-PSMA monoclonal antibody capromab for immunoPET staging of prostate cancer: Aspects of labeling chemistry and biodistribution

Tolmachev,Vladimir; Malmberg,Jennie; Estrada,Sergio; Eriksson,Olof; Orlova,Anna

doi:10.3892/ijo.2014.2376

Development of a 124I-labeled version of the anti-PSMA monoclonal antibody capromab for immunoPET staging of prostate cancer: Aspects of labeling chemistry and biodistribution

Authors:
- Vladimir Tolmachev
- Jennie Malmberg
- Sergio Estrada
- Olof Eriksson
- Anna Orlova
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Affiliations: Division of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Preclinical PET Platform, Uppsala University, Uppsala, Sweden
Published online on: April 10, 2014 https://doi.org/10.3892/ijo.2014.2376
Pages: 1998-2008

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Abstract

Correct staging of prostate cancer is an unmet clinical need. Radionuclide targeting of prostate-specific membrane antigen (PSMA) with 111In-labeled capromab pendetide (ProstaScint) is a clinical option for prostate cancer staging. We propose the use of 124I-labeled capromab to decrease the retention of radioactivity in healthy organs (due to the non-residualizing properties of the radiolabel). The use of 124I as a label should increase imaging sensitivity due to the advantages of PET as an imaging modality. Capromab targets the intracellular domain of PSMA; accumulation of radioactivity in the tumor should not depend on internalization of the antigen/antibody complex. Capromab was iodinated, and its targeting properties were compared with indium labeled counterpart in LNCaP xenografts in dual isotope mode. PSMA-negative xenografts (PC3) were used as a negative control. Radioiodinated capromab bound to PSMA specifically. Biodistribution of 125I/111In-capromab showed a more rapid clearance of iodine radioactivity from liver, spleen, kidneys, bones, colon tissue, as well as tumors. Maximum tumor uptake (13±8% ID/g for iodine and 29±9% ID/g for indium) and tumor-to-non-tumor ratios for both agents were measured 5 days post-injection (pi). High tumor accumulation and low uptake of radioactivity in normal organs were confirmed using microPET/CT 5 days pi of 124I-capromab.

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1.	Takahashi N, Inoue T, Lee J, Yamaguchi T and Shizukuishi K: The roles of PET and PET/CT in the diagnosis and management of prostate cancer. Oncology. 2:226–233. 2007. View Article : Google Scholar : PubMed/NCBI
2.	Lawrentschuk N, Davis ID, Bolton D-M and Scott AM: Positron emission tomography and molecular imaging of the prostate: an update. BJU Int. 97:923–931. 2006. View Article : Google Scholar : PubMed/NCBI
3.	Beresford MJ, Gillatt D, Benson RJ and Ajithkumar T: A systematic review of the role of imaging before salvage radio-therapy for post-prostatectomy biochemical recurrence. Clin Oncol (R Coll Radiol). 22:46–55. 2010. View Article : Google Scholar : PubMed/NCBI
4.	Schilling D, Schlemmer HP, Wagner PH, et al: Histological verification of ¹¹C-choline-positron emission/computed tomography-positive lymph nodes in patients with biochemical failure after treatment for localized prostate cancer. BJU Int. 102:446–451. 2008.
5.	Vees H, Buchegger F, Albrecht S, et al: ¹⁸F-choline and/or ¹¹C-acetate positron emission tomography: detection of residual or progressive subclinical disease at very low prostate-specific antigen values (<1 ng/ml) after radical prostatectomy. BJU Int. 99:1415–1420. 2007. View Article : Google Scholar
6.	Lilja H, Ulmert D and Vickers AJ: Prostate-specific antigen and prostate cancer: prediction, detection and monitoring. Nat Rev Cancer. 8:268–278. 2008. View Article : Google Scholar : PubMed/NCBI
7.	Raff AB, Gray A and Kast WM: Prostate stem cell antigen: A prospective therapeutic and diagnostic target. Cancer Lett. 277:126–132. 2009. View Article : Google Scholar : PubMed/NCBI
8.	Silver DA, Pellicer I, Fair WR, Heston WD and Cordon-Cardo C: Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 3:81–85. 1997.PubMed/NCBI
9.	Ulmert D, Evans MJ, Holland JP, et al: Imaging androgen receptor signaling with a radiotracer targeting free prostate-specific antigen. Cancer Discov. 2:320–327. 2012. View Article : Google Scholar : PubMed/NCBI
10.	Manyak MJ: Indium-111 capromab pendetide in the management of recurrent prostate cancer. Expert Rev Anticancer Ther. 8:175–181. 2008. View Article : Google Scholar : PubMed/NCBI
11.	Miyamoto DT, Lee RJ, Stott SL, et al: Androgen receptor signaling in circulating tumor cells as a marker of hormonally responsive prostate cancer. Cancer Discov. 2:995–1003. 2012. View Article : Google Scholar : PubMed/NCBI
12.	Eder M, Eisenhut M, Babich J and Haberkorn U: PSMA as a target for radiolabelled small molecules. Eur J Nucl Med Mol Imaging. 40:819–823. 2013. View Article : Google Scholar : PubMed/NCBI
13.	Manya MJ, Hinkle GH, Olsen JO, et al: Immunoscintigraphy with indium-111-capromab pendetide: evaluation before definitive therapy in patients with prostate cancer. Urology. 54:1058–1063. 1999. View Article : Google Scholar : PubMed/NCBI
14.	Van Dongen GA and Vosjan MJ: Immuno-positron emission tomography: shedding light on clinical antibody therapy. Cancer Biother Radiopharm. 25:375–385. 2010.PubMed/NCBI
15.	Brouwers A, Verel I, van Eerd J, et al: PET radioimmunoscintigraphy of renal cell cancer using ⁸⁹Zr-labeled cG250 monoclonal antibody in nude rats. Cancer Biother Radiopharm. 19:155–163. 2004. View Article : Google Scholar : PubMed/NCBI
16.	Nagengast WB, de Vries EG, Hospers GA, et al: In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft. J Nucl Med. 48:1313–1319. 2007. View Article : Google Scholar : PubMed/NCBI
17.	Perk LR, Stigter-van Walsum M, Visser GW, et al: Quantitative PET imaging of Met-expressing human cancer xenografts with ⁸⁹Zr-labelled monoclonal antibody DN30. Eur J Nucl Med Mol Imaging. 35:1857–1867. 2008. View Article : Google Scholar
18.	Dijkers EC, Kosterink JG, Rademaker AP, et al: Development and characterization of clinical-grade ⁸⁹Zr-trastuzumab for HER2/neu immunoPET imaging. J Nucl Med. 50:974–981. 2009. View Article : Google Scholar : PubMed/NCBI
19.	Nagengast WB, de Korte MA, Oude Munnink TH, et al: ⁸⁹Zr-bevacizumab PET of early antiangiogenic tumor response to treatment with HSP90 inhibitor NVP-AUY922. J Nucl Med. 51:761–767. 2010. View Article : Google Scholar
20.	Orlova A, Wållberg H, Stone-Elander S and Tolmachev V: On the selection of a tracer for PET imaging of HER2-expressing tumors: direct comparison of a ¹²⁴I-labeled affibody molecule and trastuzumab in a murine xenograft model. J Nucl Med. 50:417–425. 2009. View Article : Google Scholar
21.	Dijkers EC, Oude Munnink TH, Kosterink JG, et al: Biodistribution of ⁸⁹Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clin Pharmacol Ther. 87:586–592. 2010.
22.	Divgi CR, Pandit-Taskar N, Jungbluth AA, et al: Preoperative characterisation of clear-cell renal carcinoma using iodine-124-labelled antibody chimeric G250 (¹²⁴I-cG250) and PET in patients with renal masses: a phase I trial. Lancet Oncol. 8:304–310. 2007. View Article : Google Scholar : PubMed/NCBI
23.	Ruggiero A, Holland JP, Hudolin T, et al: Targeting the internal epitope of prostate-specific membrane antigen with ⁸⁹Zr-7E11 immuno-PET. J Nucl Med. 52:1608–1615. 2011. View Article : Google Scholar : PubMed/NCBI
24.	Holland JP, Divilov V, Bander NH, Smith-Jones PM, Larson SM and Lewis JS: ⁸⁹Zr-DFO-J591 for immunoPET of prostate-specific membrane antigen expression in vivo. J Nucl Med. 51:1293–1300. 2010. View Article : Google Scholar
25.	Barren RJ III, Holmes EH, Boynton AL, Misrock SL and Murphy GP: Monoclonal antibody 7E11.C5 staining of viable LNCaP cells. Prostate. 30:65–68. 1997. View Article : Google Scholar : PubMed/NCBI
26.	Tolmachev V and Orlova A: Influence of labelling methods on biodistribution and imaging properties of radiolabelled peptides for visualisation of molecular therapeutic targets. Curr Med Chem. 17:2636–2355. 2010. View Article : Google Scholar : PubMed/NCBI
27.	Koziorowski J, Henssen C and Weinreich R: A new convenient route to radioiodinated N-succinimidyl 3- and 4-iodobenzoate, two reagents for iodination of proteins. Appl Radiat Isot. 49:955–959. 1998. View Article : Google Scholar
28.	Lindmo T, Boven E, Cuttila F, Fedorko J and Bunn PA Jr: Determination of immunoractive fraction of radiolabeled monoclonal antibody by linear extrapolation to binding at infinite antigen excess. J Immunol Methods. 72:77–89. 1984. View Article : Google Scholar
29.	Khaw BA, Cooney J, Edgington T and Strauss HW: Differences in experimental tumor localization of dual-labeled monoclonal antibody. J Nucl Med. 27:1293–1239. 1986.
30.	Meijs WE, Haisma HJ, Klok RP, van Gog FB, Kievit E, Pinedo HM and Herscheid JD: Zirconium-labeled monoclonal antibodies and their distribution in tumor-bearing nude mice. J Nucl Med. 38:112–118. 1997.PubMed/NCBI
31.	Malmberg J, Sandström M, Wester K, Tolmachev V and Orlova A: Comparative biodistribution of imaging agents for in vivo molecular profiling of disseminated prostate cancer in mice bearing prostate cancer xenografts: focus on ¹¹¹In- and ¹²⁵I-labeled anti-HER2 humanized monoclonal trastuzumab and ABY-025 affibody. Nucl Med Biol. 38:1093–1102. 2011. View Article : Google Scholar : PubMed/NCBI