Abstract
Rationale: 99mTc-trofolastat (99mTc-MIP-1404), a small-molecule inhibitor of prostate-specific membrane antigen (PSMA), shows high potential to detect prostate cancer (PCa) non-invasively using single-photon-emission-computed-tomography (SPECT). We therefore wanted to assess the performance of 99mTc-trofolastat SPECT/CT in a phase 2 multi-center, multi-reader prospective study in patients with intermediate- and high-grade PCa, prior to radical prostatectomy and extended pelvic lymph node dissection, with histopathology as gold standard. Methods: 105 PCa patients with an increased risk of lymph node involvement (LNI) received a pelvic 99mTc-trofolastat SPECT/CT prior to radical prostatectomy with extended pelvic lymph node dissection. Sensitivity of 99mTc-trofolastat for detection of PCa on a patient- and lobe-basis, using visual and semi-quantitative (tumor-to-background ratio, TBR) scores and of LNI was evaluated as well as correlation of uptake within the gland to Gleason scores (GS) and assessment of the predictive potential of 99mTc-trofolastat-uptake for LNI. Results: PCa was detected in 98 patients (94%) with acceptable variability between readers. There was a significantly higher visual score and TBR in positive lobes compared to tumor-negative lobes. ROC analysis showed that visual scores more accurately discriminated lobes with GS ≤3+3 from ≥3+4, while TBRs discriminated high-grade disease from normal lobes better. Visual scores and TBRs correlated significantly with GS. 99mTc-trofolastat SPECT/CT detected LNI with sensitivity of 50%, and specificity of 87% and TBR values significantly predicted LNI with a sensitivity of 90%. Conclusion: 99mTc-trofolastat SPECT/CT detects PCa with high sensitivity in patients with intermediate- and high-risk PCa compared to histology. It has potential to be used as surrogate marker for Gleason scores and predict LNI.
- Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.