We evaluated the gastrin-releasing peptide receptor antagonist probe 68Ga-RM2 with PET/CT imaging for localization of newly diagnosed prostate cancer.1 Gastrin-releasing peptide receptor is one of the 4 known bombesin receptors overexpressed in prostate cancer.2
For that, we prospectively studied 16 men with biopsy-proven prostate cancer (2 low, 8 intermediate and 6 high risk). 68Ga-RM2 PET/CT was performed within 4 weeks following diagnostic mpMRI and within 2 weeks prior to radical prostatectomy and extended bilateral pelvic lymph node dissection.
68Ga-RM2 PET/CT, mpMRI, and 68Ga-RM2 PET/CT-mpMRI fused images ( fusion achieved using the software Hermes) were evaluated by blinded specialists using a 5-point Likert scale (1= very low, 2= low, 3=intermediate-equivocal, 4= high, 5=very high) to record the level of suspicion for cancer in each of 12 anatomical areas of the prostate for each patient. Presence of extraprostatic extension (EPE), seminal vesicle involvement (SVI) and lymph node or bone metastasis were also recorded. Whole-mount, step-section pathology of the prostate served as the reference standard. On the area-based analysis, 128 of 192 areas (66.7%) contained prostate cancer on histology. With lesions scored 4 or 5 considered positive, 68Ga-RM2 PET/CT was 84.4% sensitive, 67.2% specific, and 78.7% accurate and mpMRI was 73.4% sensitive, 82.8% specific, and 76.6% accurate; none of these parameters differed significantly. Fusing the images maximized sensitivity and accuracy (85.2% and 83.9%, respectively), and averaged specificity (81.3%). The receiver-operating characteristic area under the curve for PET visual analysis was 0.76, PET quantitative analysis 0.72, mpMRI and combined analysis of PET/CT fused to mpMRI 0.85.
PSMA is currently the reference PET tracer for prostate cancer.3, 4 However, because some prostate cancer does not express PSMA, we sought to understand the correlation between GRPr expression and PSMA expression. GRPr and PSMA expression were analyzed by immunohistochemistry on tumor paraffin sections. GRPr staining intensity ranged from 1.4 – 4 (median 2.2) and PSMA from 0.3 – 4 (median 2.8). PSMA and GRPr staining scores did not correlate (r=0.3882). Particularly, in 2 patients where PSMA staining was negative and GRPr staining was positive (scores of 2.6 and 2, respectively).
68Ga-RM2 PET/CT is promising for detection and localization of primary PCa and complements multiparametric MRI. GRPr expression appears independent from PSMA expression, suggesting that GRPr- and PSMA-targeted PET imaging may be complementary and could be used for colocalization of prostate cancer across the disease risk-spectrum.
Written by: Laure Michaud, MD1 and Karim Touijer, MD, MPH2
1. Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center
2. Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center
1. Touijer KA, Michaud L, Alvarez HAV, Gopalan A, Kossatz S, Gonen M et al. Prospective study of the radiolabeled GRPR antagonist BAY86-7548 for positron emission tomography/computerized tomography imaging of newly diagnosed prostate cancer. Eur Urol Oncol. 2019 Mar;2(2):166-173
2. Mansi R, Fleischmann A, Macke HR, Reubi JC. Targeting GRPR in urological cancers–from basic research to clinical application. Nature reviews Urology. 2013;10(4):235-44.
3. Yaxley JW, Raveenthiran S, Nouhaud FX, Samaratunga H, Yaxley WJ, Coughlin G, et al. Risk of metastatic disease on (68) Ga-PSMA PET/CT scan for primary staging of 1253 men at the diagnosis of prostate cancer. BJU international. 2019.
4. Perera M, Papa N, Roberts M, Williams M, Udovicich C, Vela I, et al. Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer-Updated Diagnostic Utility, Sensitivity, Specificity, and Distribution of Prostate-specific Membrane Antigen-avid Lesions: A Systematic Review and Meta-analysis. European urology. 2019.