Abstract
89
Objectives: We evaluated the GRPr and PSMA expression using immunohistochemical analysis (IHC) in primary prostate cancer and compared the results with 68Ga-RM2 PET/CT. Methods: As part of an ongoing prospective study evaluating 68Ga-RM2 PET/CT in primary prostate cancer, fifteen patients benefited from immunohistochemical analysis of GRPr and PSMA expression. PSA range was 1.4-64.4 ng/mL with Gleason scores ranging between 6 and 9. All patients underwent 68Ga-RM2 PET/CT no more than 2 weeks prior radical prostatectomy. PET/CT scans, from mid thighs to top of skull, were performed 60 minutes after injection of 150-200MBq 68Ga-RM2. Whole mount, step-section pathology of the prostate served as the reference standard. 5µm paraffin sections were obtained from tumor blocks. After deparaffinization, sections were incubated separately with anti-PSMA (Prointec cat#13163-1-AP 1µg/mL) and with anti-GRPr (Abcam, cat#ab39963, 5µg/mL) for 5 hours, followed by 60 minutes incubation with respectively biotinylated horse anti-rabbit and biotinylated goat anti-rabbit at 1:200 dilution. The detection was performed with DAB detection kit (Ventana Medical Systems). Slides were counterstained with hematoxylin and coverslipped with Permount (Fisher Scientific). All slides were interpreted blinded by 2 readers. Staining was classified using a 5 point-scale (0= no staining to 4= very strong staining) adapted for each antibody because GRPr staining was overall weaker than PSMA staining. Mean score of 6 fields-of view across the tumor area of each patient was scored by each reader at high magnification. Combined scoring value of the 2 readers was used for the analysis. Results: 68Ga-RM2 PET/CT scans detected 14/15 dominant tumor lesions. SUVmax of these tumors was 1.5 -27.8. GRPr staining range was 1.4-4 (average 2.4) and PSMA staining range was 0.3-4 (average 2.6). There was no correlation between PSMA and GRPr staining scores (r=0.381). For 2 patients (PSA 4.3 ng/mL G7 and PSA 6.4 ng/mL G7), there was no PSMA staining and intermediate GRPr staining (staining scores were respectively 2.6 and 2). SUVmax for the corresponding tumors on 68Ga-RM2 PET/CT was 11.3 and 8.3, respectively. Conversely, there were 2 patients (PSA 9.7 ng/mL G7 and PSA 3.2 ng/mL G7) with low GRPr staining (staining scores were 1.4), but intermediate PSMA staining (staining scores were respectively 2.5 and 2.4). SUVmax for the corresponding tumors on 68Ga-RM2 PET/CT was 4.5 and 4.4, respectively. Conclusion: GRPr expression of prostate cancer appears independent form PSMA expression. In some cases GRPr expression occurs in the absence of detectable PSMA expression on IHC. These data suggest that GRPr PET/CT could be complementary to PSMA PET/CT for detection of prostate cancer. The findings also support studies of radionuclide therapies combining GRPr and PSMA targeting agents.