Comparison of 68Ga-PSMA-617 PET/CT and 68Ga-RM2 PET/CT in Patients with Localized Prostate Cancer Who Are Candidates for Radical Prostatectomy: A Prospective, Single-Arm, Single-Center, Phase II Study

Abstract

Considering the wide range of therapeutic options for localized prostate cancer (e.g., active surveillance, radiation-beam therapy, focal therapy, and radical prostatectomy), accurate assessment of the aggressiveness and localization of primary prostate cancer lesions is essential for treatment decision making. National Comprehensive Cancer Network guidelines recognize prostate-specific membrane antigen (PSMA) PET/CT for use in initial staging of high-risk primary prostate cancer. The gastrin-releasing peptide receptor (GRP-R) is a neuropeptide receptor overexpressed by low-risk prostate cancer cells. We aimed to perform the first (to our knowledge) prospective head-to-head comparison of PSMA- and GRP-R-targeted imaging at initial staging to understand how PSMA PET and GRP-R PET can be used or combined in clinical practice. Methods: This was a prospective, single-center, diagnostic cross-sectional imaging study using anonymized, masked, and independent interpretations of paired PET/CT studies in 22 patients with ⁶⁸Ga-PSMA-617 (a radiolabeled PSMA inhibitor) and ⁶⁸Ga-RM2 (⁶⁸Ga-DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, a radiolabeled GRP-R antagonist). We enrolled patients with newly diagnosed, biopsy-proven prostate cancer. None had received neoadjuvant hormone therapy or chemotherapy, and all underwent extended pelvic lymph node dissection. Histologic findings served as a reference. Results: On a lesion-based analysis (including lesions < 0.1 cm³), ⁶⁸Ga-PSMA-617 PET/CT detected 74.3% (26/35) of all tumor lesions and ⁶⁸Ga-RM2 PET/CT detected 78.1% (25/32; 1 patient could not be offered ⁶⁸Ga-RM2 PET/CT). Paired examinations showed positive uptake of the 2 tracers in 21 of 32 lesions (65.6%), negative uptake in 5 of 32 lesions (15.6%), and discordant uptake in 6 of 32 lesions (18.8%). Uptake of ⁶⁸Ga-PSMA-617 was higher when the International Society of Urological Pathology (ISUP) score was at least 4 versus at least 1 (P < 0.0001) or 2 (P = 0.0002). There were no significant differences in uptake between ISUP scores for ⁶⁸Ga-RM2. Median ⁶⁸Ga-RM2 SUV_max was significantly higher than median ⁶⁸Ga-PSMA-617 SUV_max in the ISUP-2 subgroup (P = 0.01). Conclusion: ⁶⁸Ga-PSMA-617 PET/CT is useful to depict higher, more clinically significant ISUP score lesions, and ⁶⁸Ga-RM2 PET/CT has a higher detection rate for low-ISUP tumors. Combining PSMA PET and GRP-R PET allows for better classification of intraprostatic lesions.

Keywords: GRP-R; PET; PSMA; imaging; prostate cancer.

Graphical abstract

FIGURE 1.

Comparison of ⁶⁸Ga-PSMA-617 and ⁶⁸Ga-RM2 uptake with ISUP score. Estimates of >1 and <1 indicated higher and lower SUV_max in higher ISUP, respectively.

FIGURE 2.

⁶⁸Ga-PSMA-617 SUV_max compared with ⁶⁸Ga-RM2 SUV_max, according to ISUP groups. Estimates of >1 and <1 indicated higher and lower SUV_max, respectively, with ⁶⁸Ga-PSMA-617. For ISUP ≥ 4 group, when patient who had only ⁶⁸Ga-PSMA-617 was excluded, values were 1.32 (95% CI, 0.72–2.44) (P = 0.3459).

FIGURE 3.

Representative GRP-R and PSMA immunohistochemistry with corresponding ⁶⁸Ga-RM2 and ⁶⁸Ga-PSMA-617 PET/CT images from 2 patients. (Top) Hematoxylin, eosin, and saffron staining of ISUP-2 sample (×5 magnification) with negative PSMA immunohistochemistry (×5 magnification), negative ⁶⁸Ga-PSMA-617 PET/CT, positive GRP-R immunohistochemistry (×20 magnification), and positive ⁶⁸Ga-RM2 PET/CT. (Bottom) Hematoxylin, eosin, and saffron staining of ISUP-5 sample (×5 magnification) with positive PSMA immunohistochemistry (×5 magnification), positive ⁶⁸Ga-PSMA-617 PET/CT, negative GRP-R immunohistochemistry (×20 magnification), and negative ⁶⁸Ga-RM2 PET/CT. HES = hematoxylin, eosin, and saffron; IHC = immunohistochemistry. Intensity-scale bars indicate SUV.

FIGURE 4.

⁶⁸Ga-RM2 maximum-intensity projection (A); ⁶⁸Ga-PSMA-617 maximum-intensity projection (B); hematoxylin, eosin, and saffron staining of histologic slice from prostatectomy of patient 7 with manual demarcation of tumor lesions (C); ⁶⁸Ga-RM2 transaxial PET/CT image (D); and ⁶⁸Ga-PSMA-617 transaxial PET/CT image (E). Anterior ISUP-3 lesion and right basal ISUP-2 lesion were seen on histology, with 2 small lesions < 0.1 cm³ (C). ⁶⁸Ga-RM2 PET/CT and ⁶⁸Ga-PSMA-617 PET/CT showed similar uptake on ISUP-3 lesion: SUV_max was 6.7 for ⁶⁸Ga-RM2 and 6.8 for ⁶⁸Ga-PSMA-617 (arrowheads). ⁶⁸Ga-RM2 was the only radiopharmaceutical able to detect ISUP-2 lesion well (arrows): SUV_max was 7.3 for ⁶⁸Ga-RM2 and 3.4 for ⁶⁸Ga-PSMA-617. HES = hematoxylin, eosin, and saffron.