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

Abstract

Abstract. Correct staging of prostate cancer is an unmet clinical need. Radionuclide targeting of prostate-specific membrane antigen (PSMA) with 111 In-labeled capromab pendetide (ProstaScint) is a clinical option for prostate cancer staging. We propose the use of 124 I-labeled capromab to decrease the retention of radioactivity in healthy organs (due to the non-residualizing properties of the radiolabel). The use of 124 I 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 125 I/ 111 In-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 124

Comparative Evaluation of Radioiodine and Technetium-Labeled DARPin 9_29 for Radionuclide Molecular Imaging of HER2 Expression in Malignant Tumors

“…This study utilized iodine-125 ( T 1/2 = 59.4 d) because this radionuclide is convenient for preclinical development due to long half-life and low energy of emitted photons. Our experience suggests that the labeling protocol might be applied with a minimal reoptimization for labeling with iodine-123 ( T 1/2 = 13.3 h) and iodine-124 ( T 1/2 = 4.18 d) for clinical SPECT or PET applications, respectively [ 46 , 47 ].…”

Feasibility of Affibody Molecule-Based PNA-Mediated Radionuclide Pretargeting of Malignant Tumors

“…In the case of the dual label study, the whole spectrum of each sample was recorded. The use of γ-spectroscopy enabled the biodistribution measurement of 111 In and 125 I in each animal independently 26 .…”

Influence of protein properties and protein modification on biodistribution and tumor uptake of anticancer antibodies, antibody derivatives, and non‐Ig scaffolds

“…However, indirectly radiolabeled protein drugs, with, for example, 89 Zr or 111 In, are often catabolized into charged radiocatabolites that remain trapped intracellularly . Consequently, indirect labeling results in higher tumor signals and is therefore a more sensitive approach to visualize tumor uptake . Its use additionally results in higher signals in normal tissue, which is for antibodies and their fragments most pronounced in liver, spleen, and kidneys .…”

“…Consequently, indirect labeling results in higher tumor signals and is therefore a more sensitive approach to visualize tumor uptake . Its use additionally results in higher signals in normal tissue, which is for antibodies and their fragments most pronounced in liver, spleen, and kidneys . Extremely high organ uptake may hamper the visualization of tumor uptake in tumors that are located in or in close proximity of these organs.…”

“…[67][68][69][70][71][72] Its use additionally results in higher signals in normal tissue, which is for antibodies and their fragments most pronounced in liver, spleen, and kidneys. [67][68][69][70][71][72] Extremely high organ uptake may hamper the visualization of tumor uptake in tumors that are located in or in close proximity of these organs. As charged radiocatabolites remain trapped intracellularly after internalization and catabolism, their use could provide additional insight in catabolic sites of therapeutic proteins and delivery of toxic drugs by, for example, ADCs.…”