Quantitative ImmunoPET of Prostate Cancer Xenografts with ⁸⁹Zr- and ¹²⁴I-Labeled Anti-PSCA A11 Minibody

Abstract

Prostate stem cell antigen (PSCA) is expressed on the cell surface in 83%–100% of local prostate cancers and 87%–100% of prostate cancer bone metastases. In this study, we sought to develop immunoPET agents using 124I- and 89Zr-labeled anti-PSCA A11 minibodies (scFv-CH3 dimer, 80 kDa) and evaluate their use for quantitative immunoPET imaging of prostate cancer. Methods A11 anti-PSCA minibody was alternatively labeled with 124I- or 89Zr-desferrioxamine and injected into mice bearing either matched 22Rv1 and 22Rv1× PSCA or LAPC-9 xenografts. Small-animal PET data were obtained and quantitated with and without recovery coefficient–based partial-volume correction, and the results were compared with ex vivo biodistribution. Results Rapid and specific localization to PSCA-positive tumors and high-contrast imaging were observed with both 124I-and 89Zr-labeled A11 anti-PSCA minibody. However, the differences in tumor uptake and background uptake of the radiotracers resulted in different levels of imaging contrast. The nonresidualizing 124I-labeled minibody had lower tumor uptake (3.62 ± 1.18 percentage injected dose per gram [%ID/g] 22Rv1×PSCA, 3.63 ± 0.59 %ID/g LAPC-9) than the residualizing 89Zr-labeled minibody (7.87 ± 0.52 %ID/g22Rv1×PSCA, 9.33 ±0.87 %ID/gLAPC-9, P <0.0001 for each), but the 124I-labeled minibody achieved higher imaging contrast because of lower nonspecific uptake and better tumor–to–soft-tissue ratios (22Rv1×PSCA:22Rv1 positive-to-negative tumor, 13.31 ± 5.59 124I-A11 and 4.87 ± 0.52 89Zr-A11, P = 0.02). Partial-volume correction was found to greatly improve the correspondence between small-animal PET and ex vivo quantification of tumor uptake for immunoPET imaging with both radionuclides. Conclusion Both 124I-and 89Zr-labeled A11 anti-PSCA minibody showed high-contrast imaging of PSCA expression in vivo. However, the 124I-labeled A11 minibody was found to be the superior imaging agent because of lower nonspecific uptake and higher tumor–to–soft-tissue contrast. Partial-volume correction was found to be essential for robust quantification of immunoPET imaging with both 124I- and 89Zr-labeled A11 minibody.

89Zr-Labeled Versus 124I-Labeled αHER2 Fab with Optimized Plasma Half-Life for High-Contrast Tumor Imaging In Vivo

“…Furthermore, experiments with the head and neck squamous cell carcinoma-selective chimeric antibody U36, labeled with either 89 Zr or 124 I, resulted in significantly higher uptake in tumor and liver for 89 Zr (30). In a similar comparison of the 89 Zr-and 124 I-labeled versions of the anti-prostate stem cell antigen minibody A11 in mice carrying prostate stem cell antigen-positive tumors, higher tumor uptake was again found for the residualizing radiometal, whereas better imaging contrast was seen for the 124 I-labeled minibody (31).…”

Anti-MET ImmunoPET for Non–Small Cell Lung Cancer Using Novel Fully Human Antibody Fragments

“…The kidney uptakes were not shown in the biodistribution results because the signals were too high to be accurately measured by the gamma counter. However, we estimated the uptake levels to be about 83 – 104 %ID/g (Hcc827 vs. C6 group: 85 ± 1 %ID/g; Hcc827-GR6 vs. C6 group: 99 ± 2 %ID/g; Hcc827-GR6 vs. Hcc827 group: 98 ± 9 %ID/g) by image quantitation using a previously described method (29). The high kidney uptakes are due to the renal clearance of these low molecular weight cys-diabody proteins.…”

“…About half of the Hcc827-GR6 tumors were cystic, and the biodistribution of these tumors was calculated excluding the cystic fluid. The radioactivities of some kidney samples were too high to be accurately measured by gamma counting, so the uptake levels were estimated by image quantitation using previously described method (29). …”

Applications of ImmunoPET: Using 124I-Anti-PSCA A11 Minibody for Imaging Disease Progression and Response to Therapy in Mouse Xenograft Models of Prostate Cancer

“…Radiolabeling, purification, and immunoreactivity were performed as previously described except for the much higher specific activity used here (~30–50µCi/µg) (32). 44 hours after A11 minibody injection, the mice again received microPET/CT scans.…”

“…44 hours after A11 minibody injection, the mice again received microPET/CT scans. The mice were then either kept for serial imaging at later time points or at the last time point sacrificed for biodistribution as previously described (32). The images were analyzed using the same method as for the 18 F-Fluoride bone scans.…”