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

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 I-124- and Zr-89-labeled anti-PSCA A11 minibodies (scFv-C(H)3 dimer, 80 kDa) and evaluate their use for quantitative immunoPET imaging of prostate cancer. Methods: A11 anti-PSCA minibody was alternatively labeled with I-124- or Zr-89-desferrioxamine and injected into mice bearing either matched 22Rv1 and 22Rv1x 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 I-124- and Zr-89-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 I-124- labeled minibody had lower tumor uptake (3.62 +/- 1.18 percentage injected dose per gram [%lD/g] 22Rv1xPSCA, 3.63 +/- 0.59 %lD/g LAPC-9) than the residualizing Zr-89-labeled minibody (7.87 +/- 0.52 %lD/g 22Rv1xPSCA, 9.33 +/- 0.87 %lD/g LAPC-9, P<0.0001 for each), but the I-124-labeled minibody achieved higher imaging contrast because of lower nonspecific uptake and better tumor-to-soft-tissue ratios (22Rv1xPSCA:22Rv1 positive-to-negative tumor, 13.31 +/- 5.59 I-124-A11 and 4.87 +/- 0.52 Zr-89-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 I-124- and Zr-89-labeled A11 anti-PSCA minibody showed high-contrast imaging of PSCA expression in vivo. However, the I-124-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 I-124- and Zr-89-labeled A11 minibody.