A Prospective Pilot Study of ⁸⁹ Zr-J591/Prostate Specific Membrane Antigen Positron Emission Tomography in Men with Localized Prostate Cancer Undergoing Radical Prostatectomy

Abstract

Purpose In this pilot study we explored the feasibility of 89Zr labeled J591 monoclonal antibody positron emission tomography of localized prostate cancer. Materials and Methods Before scheduled radical prostatectomy 11 patients were injected intravenously with 89Zr-J591, followed 6 days later by whole body positron emission tomography. Patients underwent surgery the day after imaging. Specimens were imaged by ex vivo micro positron emission tomography and a custom 3 Tesla magnetic resonance scanner coil. Positron emission tomography images and histopathology were correlated. Results Median patient age was 61 years (range 47 to 68), median prostate specific antigen was 5.2 ng/ml (range 3.5 to 12.0) and median biopsy Gleason score of the 11 index lesions was 7 (range 7 to 9). On histopathology 22 lesions were identified. Median lesion size was 5.5 mm (range 2 to 21) and median Gleason score after radical prostatectomy was 7 (range 6 to 9). Eight of 11 index lesions (72.7%) were identified by in vivo positron emission tomography. Lesion identification improved with increasing lesion size for in vivo and ex vivo positron emission tomography (each p <0.0001), and increasing Gleason score (p = 0.14 and 0.01, respectively). Standardized uptake values appeared to correlate with increased Gleason score but not significantly (p = 0.19). Conclusions To our knowledge this is the first report of 89Zr-J591/prostate specific membrane antigen positron emission tomography in localized prostate cancer cases. In this setting 89Zr-J591 bound to tumor foci in situ and positron emission tomography identified primarily Gleason score 7 or greater and larger tumors, likely corresponding to clinically significant disease warranting definitive therapy. A future, larger clinical validation trial is planned to better define the usefulness of 89Zr-J591 positron emission tomography for localized prostate cancer.

Prostate-Specific Membrane Antigen–Targeted Radiohalogenated PET and Therapeutic Agents for Prostate Cancer

“…The most widely accepted imaging modalities used include MRI for the evaluation of patients who have clinically localized primary disease (2) or who are thought to harbor recurrent PC limited to the pelvis (3), contrast-enhanced CT, and 99m Tc-methylene diphosphonate bone scanning for the evaluation of metastatic disease in primary and recurrent PC (4). Additionally, in Europe, PET imaging with 11 C-choline or 18 F-fluorocholine has recently gained acceptance for the workup of recurrent PC.…”

“…Ultimately, the targeting of an intracellular epitope combined with the limitations in spatial resolution and quantification that are inherent to single-photon-emitting radionuclides prevented the acquisition of suitably high-quality images. However, PSMA remained a promising target, and more recent radiolabeled monoclonal antibodies against an extracellular PSMA epitope (18,19) as well as single-photon-emitting (20,21) and positron-emitting (22)(23)(24)(25) small-molecule inhibitors of PSMA have been extensively explored. Results continue to suggest that PSMA-targeted imaging of PC is a promising alternative to conventional imaging.…”

Immuno-PET Imaging of CD30-Positive Lymphoma Using 89Zr-Desferrioxamine–Labeled CD30-Specific AC-10 Antibody

“…The radiotracer was found to be stable, with high immunoreactivity in vitro and in vivo. In terms of absolute tumor uptake and relative tumor-to-background tissue contrast ratios, the performance of 89 Zr-DFO-AC-10 for immuno-PET imaging of CD30-positive lesions was equivalent to the reported performance of many other 89 Zr-DFO-mAbs, including 89 Zr-DFO-J591 for imaging prostate-specific membrane antigen in prostate cancer (21,25,26), as well as 89 Zr-trastuzumab for imaging HER2/neu (27) and 89 Zrbevacizumab imaging VEGF-A in breast cancers (28).…”

Metabolomic Imaging for Human Prostate Cancer Detection using MR Spectroscopy at 7-T

“…To date, highest detection rates (80-90%) are achieved in metastatic recurrent PCa 33,34 . Furthermore, the degree of expression of PSMA was found to correlate with tumor aggressiveness, hence PSMA might prospectively serve as a prognostic marker 35,36,37,38 .…”