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Phase I trial of zirconium 89 (Zr89) radiolabeled J591 in metastatic castration-resistant prostate cancer (mCRPC).
J Clin Oncol 31, 2013 (suppl 6; abstr 31)
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: Presently, there are no means of accurately and reproducibly imaging bone metastases for patients with mCRPC. We are investigating a prostate-specific imaging method that can directly visualize metastases using PSMA as a target and Zr89 radiolabeled anti-PSMA antibody J591 as a tracer. Following the FDA roadmap for biomarker development, we report the first human data on the tracer and its preliminary analytic validation. Methods: 5 mCi of Zr89-J591 was administered intravenously and 4 serial PET/CT scans were obtained within the following time intervals post-injection: 2-4 hours, 18-30 hours, 2-5 days, and 6-7 days. Pharmacokinetic (PK) sampling occurred at 5, 30, and 60 minutes post-injection, and at each PET scan. Patients underwent standard cross-sectional imaging, bone scintigraphy, and FDG PET scanning. Metastatic sites were biopsied in order of preference: Zr89-J591 and FDG positivity, then Zr89-J591 and FDG mismatch, and lastly standard imaging and any PET mismatch. Results: Ten patients were scanned, 132 Zr89-J591 positive sites were detected, and 12 lesions (5 bone, 6 node, 1 lung) in 8 patients were biopsied. Tissue correlation: 12/12 biopsies were positive for cancer. 11/12 biopsied lesions (5 bone, 5 node, 1 lung) were positive on Zr89-J591 imaging. 10/12 were positive by standard scans or FDG. 1 lesion was negative by Zr89-J591 PET, but positive by other modalities. Immunokinetics: Blood clearance T1/2α: 7 +/- 4.5 h (1.1-14 h); T1/2β: 62 +/- 13 h (51-89 h); Whole body clearance T1/2: 219 +/- 48 h (153-317 h). Dosimetry: Maximum retention in liver 8 +/- 1.5 SUV; Kidney 4.1 +/- 0.8 SUV; Tumor 8.2 +/- 6.5 SUV (mean SUV in bone 11.13 +/- 7.57 vs. soft tissue 4.31 +/- 2.59). Optimal time for patient imaging after injection, in terms of tumor to background ratios was 7 +/- 1 days. Conclusions: Zr89-J591 imaging demonstrates excellent tumor localization, pathology correlation, and can demonstrate the presence of tumor even when lesions are negative by standard imaging or FDG PET imaging. PK properties of the tracer have been defined. Use of Zr89-J591 to direct biopsies of metastases provides excellent yield. Further studies to examine reproducibility and post-treatment effects are planned. Clinical trial information: NCT01543659.
Abstracts by Michael Morris:
The impact of chemotherapy use on financial strain among stage III colorectal cancer patients: A population-based survey.
Tumor-directed PET imaging of bone metastases in metastatic castration-resistant prostate cancer (mCRPC) using Zr-89 labeled anti-prostate specific membrane antigen (PSMA) antibody J591.Category: Genitourinary Cancer - Prostate Cancer
Presentations by Michael Morris:
Phase I trial of zirconium 89 (Zr89) radiolabeled J591 in metastatic castration-resistant prostate cancer (mCRPC).Session: General Poster Session A: Prostate Cancer (General Poster Session)
A phase I/IIa study of the safety and efficacy of radium-223 chloride (Ra-223) with docetaxel (D) for castration-resistant prostate cancer (CRPC) patients with bone metastases.Session: Genitourinary Cancer (General Poster Session)
Meeting: 2012 ASCO Annual Meeting
Abstract No: 4568
Session: Genitourinary (Prostate) Cancer (Poster Discussion Session)