A Phase I Pilot Study of 99MTC-MIP-1404 Single Photon Emission Computed Tomography (SPECT)/CT Imaging in Men with Prostate Cancer Undergoing Radical Prostatectomy
David Green, Joseph Osborne, Anastasia Nikolopoulou, Shankar Vallabhajosula, Stanley Goldsmith, Constantin S Friedman, Sagit Goldenberg, Brian D Robinson, John Babich, Douglas Scherr. Weill Cornell Medical College, New York, NY; Molecular Insight Pharmaceuticals, Inc., Cambridge, MA
Background: Imaging prostate cancer (PCa) lesions within the gland is challenging with conventional imaging modalities. Theoretically, prostate-specific membrane antigen (PSMA)-based imaging could help delineate not only specific lesions but also differentiate between aggressive and indolent disease (as PSMA is up-regulated in aggressive cancers). Using the small molecule antagonist to PSMA, 99mTc-MIP-1404 (study drug), we conducted a Phase I Single Photon Emission Computed Tomography (SPECT)/CT imaging trial in patients scheduled for radical prostatectomy (RP). We hypothesized that our targeted imaging would pre-operatively predict PCa lesion location.
Design: Patients diagnosed with localized PCa and scheduled for RP participated in this study. Inclusion criteria were: a) Gleason ≥7 with ≥3 biopsy cores positive and at least one core ≥30% involved with PCa OR b) presence of any Gleason ≥8. Within two weeks of RP, subjects were injected with a single IV dose of study drug followed by SPECT/CT scan at 3-6 hours. Prostates were processed in standard fashion and stained for PSMA. SPECT studies and pathologic specimens were analyzed for the presence of PCa on a six sector grid (Right and Left; Base/Mid/Apex).
Results: Eight patients completed the study yielding 48 evaluable prostate sectors. 40 of 48 sectors contained a PSMA+ prostate cancer nodule. The dominant tumor nodule was detectable by imaging in all 8 patients and correlated with pathological location within the prostate. As expected, imaging detection, in part, depended upon both PSMA expression level and tumor volume (Fig.1). When stratified by Gleason grade, imaging detection occurred in 3/6(50%) Gleason 6, 9/16(56%) Gleason 3+4, 4/6(66%) Gleason 4+3, and 9/12(75%) Gleason 9 regions.
Conclusions: Our novel PSMA-based small molecule SPECT imaging may be able to visually distinguish aggressive from indolent disease as evidenced by the trend towards improved detection with increasing Gleason grade. Further development of this modality should include exploring its role in guiding focal therapy. Limitations of our study include the small sample size and the limits of SPECT resolution.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 180, Tuesday Afternoon