Prospective Study of the Radiolabeled GRPR Antagonist BAY86-7548 for Positron Emission Tomography/Computed Tomography Imaging of Newly Diagnosed Prostate Cancer

Abstract

Background: Current imaging techniques may not detect all prostate cancer (PCa) lesions.

Objective: To evaluate positron emission tomography (PET)/computed tomography (CT) using the radiolabeled GRPR antagonist probe BAY86-7548 (⁶⁸Ga-RM2) for localization of newly diagnosed PCa in comparison with multiparametric magnetic resonance imaging (mpMRI), histopathology, and immunohistochemistry (IHC).

Design, setting, and participants: This was a prospective study of 16 men with biopsy-proven PCa (2 low, 8 intermediate, and 6 high risk). ⁶⁸Ga-RM2 PET/CT was performed within 4 wk after mpMRI and within 2 wk before radical prostatectomy and extended bilateral pelvic lymph node dissection.

Outcome measurements and statistical analysis: The presence of cancer was evaluated by blinded specialists using a 5-point Likert scale, with lesions scoring 4 or 5 considered positive, on ⁶⁸Ga-RM2 PET/CT, mpMRI, and ⁶⁸Ga-RM2 PET/CT-mpMRI fused images for each of 12 anatomic areas of the prostate. Whole-mount, step-section pathology served as the reference standard. Expression of GRPR and prostate-specific membrane antigen (PSMA) was analyzed via IHC of tumor paraffin sections.

Results and limitations: Of 192 areas analyzed, 128 contained cancer. The sensitivity, specificity, and accuracy of ⁶⁸Ga-RM2 PET/CT imaging and mpMRI did not differ significantly; fusing the images maximized the sensitivity and accuracy (85.2% and 83.9%, respectively) and averaged the specificity (81.3%). The area under the receiver operating characteristic curve was 0.76 for PET visual analysis, 0.72 for PET quantitative analysis, 0.76 for mpMRI, and 0.85 for combined PET/CT and mpMRI analysis. ⁶⁸Ga-RM2 uptake did not correlate with Gleason score. IHC analysis revealed weaker staining for GRPR than for PSMA, and the expression of these markers was not correlated (r=0.3882). The major limitation is the small sample size.

Conclusions: ⁶⁸Ga-RM2 PET/CT is promising for detection and localization of primary PCa, and complements mpMRI. GRPR expression appears to be independent from PSMA expression, suggesting that GRPR- and PSMA-targeted PET imaging may be complementary.

Patient summary: This pilot prospective study shows that a positron emission tomography probe that binds to a marker of prostate cancer, GRPR, improves the ability of magnetic resonance imaging to detect prostate cancer.

Keywords: Gastrin-releasing peptide receptor; Imaging; Multiparametric magnetic resonance imaging; Positron emission tomography/computed tomography; Prostate-specific membrane antigen.