Diagnosis of recurrent prostate cancer with PET/CT imaging using the gastrin-releasing peptide receptor antagonist 68Ga-RM2: Preliminary results in patients with negative or inconclusive [18F]Fluoroethylcholine-PET/CT

Abstract

Purpose/background: [¹⁸F]fluoroethylcholine (¹⁸FECH) has been shown to be a valuable PET-tracer in recurrent prostate cancer (PCa), but still has limited accuracy. RM2 is a gastrin-releasing peptide receptor (GRPr) antagonist that binds to GRPr on PCa cells. Recent studies suggest that GRPr imaging with PET/CT is a promising technique for staging and restaging of PCa. We explore the value of GRPr-PET using the ⁶⁸Ga-labeled GRPr antagonist RM2 in a selected population of patients with biochemically recurrent PCa and a negative/inconclusive ¹⁸FECH-PET/CT.

Material and methods: In this retrospective study 16 men with biochemical PCa relapse and negative (n = 14) or inconclusive (n = 2) ¹⁸FECH-PET/CT underwent whole-body ⁶⁸Ga-RM2-PET/CT. Mean time from ¹⁸FECH-PET/CT to ⁶⁸Ga-RM2-PET/CT was 6.1 ± 6.8 months. Primary therapies in these patients were radical prostatectomy (n = 13; 81.3%) or radiotherapy (n = 3; 18.7%). 14/16 patients (87.5%) had already undergone salvage therapies because of biochemical relapse prior to ⁶⁸Ga-RM2-PET/CT imaging. Mean ± SD PSA at ⁶⁸Ga-RM2-PET/CT was 19.4 ± 53.5 ng/ml (range 1.06-226.4 ng/ml).

Results: ⁶⁸Ga-RM2-PET/CT showed at least one region with focal pathological uptake in 10/16 patients (62.5%), being suggestive of local relapse (n = 4), lymph node metastases (LNM; n = 4), bone metastases (n = 1) and lung metastasis with hilar LNM (n = 1). Seven of ten positive ⁶⁸Ga-RM2 scans were positively confirmed by surgical resection and histology of the lesions (n = 2), by response to site-directed therapies (n = 2) or by further imaging (n = 3). Patients with a positive ⁶⁸Ga-RM2-scan showed a significantly higher median PSA (6.8 ng/ml, IQR 10.2 ng/ml) value than those with a negative scan (1.5 ng/ml, IQR 3.1 ng/ml; p = 0.016). Gleason scores or concomitant antihormonal therapy had no apparent impact on the detection of recurrent disease.

Conclusion: Even in this highly selected population of patients with known biochemical recurrence but negative or inconclusive ¹⁸FECH-PET/CT, a ⁶⁸Ga-RM2-PET/CT was helpful to localize PCa recurrence in the majority of the cases. Thus, ⁶⁸Ga-RM2-PET/CT deserves further investigation as a promising imaging modality for imaging PCa recurrence.

Keywords: 68Ga-RM2; Bombesin receptor; Gastrin-releasing peptide receptor (GRPr); PET/CT; Prostate cancer.