Pathologic correlation of 89Zr-Df-IAB2M antiprostate-specific membrane antigen (PSMA) minibody in patients with metastatic prostate cancer.

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220 Background: IAB2M is a novel anti-PSMA minibody (Mb) based on the humanized J591 antibody that targets the extracellular domain of PSMA. The Mb has been engineered to remove Fc-Rn interactions and reduce the molecular weight relative to J591. The result is faster blood pool clearance, for a more favorable imaging schedule, while retaining bivalent targeting of PSMA. We have previously reported on the pharmacokinetics, dosimetry, and lesion uptake of IAB2M(Pandit-Taskar et al, WMIS 2014). Here we report the correlation between imaging and pathology of biopsies of PSMA avid lesions. Methods: Following standard imaging (SI) of CT/MRI, bone scintigraphy (BS), and FDG PET, 5 mCi of 89Zr-Df-IAB2M was administered intravenously. Escalating minibody doses of 10, 20, and 50 mg were delivered, with cohort expansion at 10 and 20 mg. Whole body PET/CT scans were serially performed at various time points:1-2 h, 24 h, 48 h, and 72-144 h post injection. Metastases identified on PET were confirmed, where possible, with bx’s in the following preference: concordant IAB2M and FDG positivity, IAB2M, and FDG mismatch, or a mismatch between SI and any PET. Results: 24 patients (pts) with metastatic prostate cancer were scanned (11 at 10, 7 at 20, and 6 at 50 mg Mb doses). A total of 15 bxs (7 soft tissue, 8 bone) were performed on 14 pts; the histopathologic correlation is summarized in the table below. 13 lesions were identified by IAB2M, 11 by FDG, and 14 by SI. Of these, 12/13 (92.3%), 10/11 (90.9%), 12/14 (85.7%) were biopsy positive for cancer, respectively. 2 bone lesions were not identified by IAB2M, evident on other imaging modalities, and were both neg by bx. Overall bx concordance (pos/pos, neg/neg) with imaging was: IAB2M 14/15 (93%) vs. BS/CT 13/15 (86%) vs. FDG 12/15 (80%). Conclusions: An ongoing analysis of IAB2M imaging showed a high concordance with pathologic findings in patients with metastatic prostate cancer. Clinical trial information: NCT01923727. [Table: see text]