⁶⁸Ga-PSMA PET/CT Detects the Location and Extent of Primary Prostate Cancer

Abstract

We evaluated the accuracy of PET/CT with 68 Ga-PSMA-HBED-CC-a 68 Ga-conjugated ligand of human prostate-specific membrane antigen (PSMA)-to localize cancer in the prostate and surrounding tissue at initial diagnosis. Methods: Twenty-one patients with biopsy-proven prostate cancer underwent 68 Ga-PSMA-HBED-CC ( 68 Ga-PSMA) PET/CT at a median of 4 d (range, 0-47 d) before radical prostatectomy. Based on a 6-segment model, the Gleason score and proportion of tumor tissue within each segment (segmental tumor burden, or STB) as determined by histopathology (STB HP ) were correlated with SUV max and STB as determined by different SUV cutoffs for 68 Ga-PSMA PET (STB ). Furthermore, the involvement of seminal vesicles and other extracapsular extension were assessed by histopathology and PET/CT. Results: Histopathology-positive segments (n 5 100 of 126; 79%) demonstrated a significantly higher mean ± SD SUV max (11.8 ± 7.6) than histopathology-negative segments (4.9 ± 2.9; P , 0.001). Receiver-operating-characteristic analysis revealed an optimal SUV max cutoff of 6.5 for discrimination of histopathology-positive segments from histopathology-negative segments (area under the curve, 0.84; P , 0.001), which gave 67% sensitivity, 92% specificity, a 97% positive predictive value, a 42% negative predictive value, and 72% accuracy. STB PET3 as determined by (2 · blood SUV) 1 (2 · SD) correlated best with STB HP (Pearson ρ 5 0.68; P , 0.001; mean difference ± SD, 19% ± 15%). PET/CT correctly detected invasion of seminal vesicles (n 5 11 of 21 patients; 52%) with 86% accuracy and tumor spread through the capsule (n 5 12; 57%) with 71% accuracy. Conclusion: 68 Ga-PSMA PET/CT accurately detected the location and extent of primary prostate cancer. Our preliminary findings warrant further investigation of 68 Ga-PSMA PET/CT in conjunction with needle biopsy.

PSMA Ligands for PET Imaging of Prostate Cancer

“…These studies demonstrated relatively similar results, with a significantly higher 68 Ga-PSMA-11 uptake in positive segments than in negative segments (SUV max of 11.8 vs. 4.9 and 11.0 vs. 2.7, respectively, P , 0.001 each) (50,51). Results from combining 68 Ga-PSMA-11 and multiparametric MRI on 53 preoperative intermediate-/high-risk patients indicated a potential for targeting biopsies.…”

“…With regard to intraprostatic tumor localization by 68 Ga-PSMA-11 PET/CT, imaging findings were correlated with histopathology using segment-or voxel-based approaches in several studies (50)(51)(52). These studies demonstrated relatively similar results, with a significantly higher 68 Ga-PSMA-11 uptake in positive segments than in negative segments (SUV max of 11.8 vs. 4.9 and 11.0 vs. 2.7, respectively, P , 0.001 each) (50,51).…”

Prostate-Specific Membrane Antigen Ligands for Imaging and Therapy

“…Increasing numbers of studies have investigated the potential of 68 Ga-PSMA-11 for intraprostatic tumor localization (97)(98)(99)(100)(101)(102). For example, on the basis of a 6-segment model per slice, histopathologically positive segments (n 5 100 in 21 patients) had significantly higher 68 Ga-PSMA-11 uptake than negative segments (SUV max , 11.8 vs. 4.9), suggesting an SUV max of 6.5 as an optimal discriminator (sensitivity of 67% and specificity of 92% for the detection of tumor-involved segments) (97).…”

“…For example, on the basis of a 6-segment model per slice, histopathologically positive segments (n 5 100 in 21 patients) had significantly higher 68 Ga-PSMA-11 uptake than negative segments (SUV max , 11.8 vs. 4.9), suggesting an SUV max of 6.5 as an optimal discriminator (sensitivity of 67% and specificity of 92% for the detection of tumor-involved segments) (97). Other retrospective studies investigating 6 and 9 patients and using segment and voxelwise approaches reported similar results (98,101).…”

Will GRPR Compete with PSMA as a Target in Prostate Cancer?

“…Only 5%-10% of primary PCa lesions have been shown to be PSMA-negative (2), making this class of radiopharmaceutical suitable for diagnosis of primary PCa and for initial staging (3,4). Use for noninvasive tumor grading has also been reported (3).…”