Introduction

Prostate cancer (PCa) is the second most common cancer in men worldwide¹. While histological confirmation is required for the diagnosis of PCa, multi-parametric MRI (mp-MRI) is commonly implemented in the clinical routine to detect the primary tumor, guide biopsies and define the local extent of the disease^2,3. PET molecular imaging is another valid imaging approach in PCa staging, with new PET tracers bearing potential to improve diagnosis, staging and follow-up of PCa^4–6. Hybrid PET/MRI allows the simultaneous acquisition of metabolic, structural, and functional imaging information concerning PCa status in a whole-body single session examination. The aim of the present study is to investigate the synergic role of ⁶⁸Ga-PSMA PET, ⁶⁸Ga-DOTA-RM2 PET and MRI in PCa staging using a hybrid PET/MR scanner.

Methods

Thirteen patients (mean age 66.74, sd 8.77) with biopsy-proven PCa underwent ⁶⁸Ga-PSMA PET/MRI and ⁶⁸Ga-DOTA-RM2 PET/MRI in two different days for staging purpose. Radical prostatectomy was then performed. The PSMA protocol consisted in a high statistic (HS) pelvic PSMA PET bed, during which T2, DWI, DCE sequences were acquired and a Total Body PET acquisition with LAVA-flex and DWI at each bed. The ⁶⁸Ga-DOTA-RM2 protocol consisted in a HS pelvic ⁶⁸Ga-DOTA-RM2 PET bed during which T2 sequence was acquired and Total Body PET acquisition with LAVA-flex. TNM classification based on image findings was performed and quantitative imaging parameters were collected for each scan. Specifically, on the pelvic HS PET beds, VOIs on the tumor lesions were segmented on the ⁶⁸Ga-PSMA PET, ⁶⁸Ga-DOTA-RM2 PET and on T2 MR images by an expert Nuclear Medicine physician and an expert radiologist. After having coregistered PSMA and DOTA-RM2 studies, DICE score between VOIs was computed. Furthermore, the histological data derived from prostatectomy were used as gold standard to validate intraprostatic findings as well as local extension of the disease.

Results

Figure 1 shows an example of study in a 53ys old patient. The analysis of semi-quantitative parameters of prostate uptake extracted from HS ⁶⁸Ga-PSMA images showed a mean SUVmax of 19.18 (sd: 10.920), SUVmean40-50-60% of 11.597, 12.885, 14.569, respectively (sd: 6.791, 7.587, 8.434, respectively), MTV40-50-60% of 1.613, 1.129, 0.712, respectively (sd: 0.910, 0.813, 0.707, respectively). The analysis of semi-quantitative parameters of prostate uptake extracted from HS ⁶⁸Ga-DOTA-RM2 images showed a mean SUVmax of 15.323 (sd: 7.827), SUVmean40-50-60% of 9.745, 10.782, 11.54, respectively (sd: 5.204, 5.732, 6.003, respectively), MTV40-50-60% of 2.899, 2.140, 1.664, respectively (sd: 1.697,1.436,1.289, respectively).
Finally, ADCmean and ADCmin was measured for each patient using the corresponding VOIs defined on the T2 images. Mean ADCmean value of the primary tumors was 0.834 10^-3 mm²/s (sd: 0.138), while mean ADCmin value was 0.516 10^-3 mm²/s (sd: 0.152) and mean lesion volume was 1.713 cm³ (sd: 1.087). Figure 2 shows the DICE indexes for each patients. Figure 3 shows two examples of concordant and discordant contouring on DICE analysis.
All imaging modalities detected the primary intraprostatic lesion, being concordant in 12/13 regarding the intraprostatic site of disease; in 1/13 patients ⁶⁸Ga-PSMA PET identified the primary tumour in the left side of the prostate, while ⁶⁸Ga-DOTA-RM2 PET and MRI were concordant with histology in identifying the primary tumour on the right lobe. Regarding seminal vescicle invasion (SVI), in 11/13 patients ⁶⁸Ga-PSMA, ⁶⁸Ga-DOTA-RM2 PET and MRI did not detect any involvement, being concordant with histology; in 2/13, histology identified SVI not seen at imaging. The validation of extracapsular extension (ECE) with histology has been performed only for MRI, as both ⁶⁸Ga-PSMA and ⁶⁸Ga-DOTA-RM2 PET are not suitable to identify ECE because of their limited spatial resolution. Histology and MRI were concordant in 5/13 patients (2/13 positive and 3/13 negative for ECE) and discordant in 8/13 (5/13 with ECE at histology but not on MRI and 3/13 positive on MRI but not confirmed at histology).

Discussion and conclusions

These preliminary results suggest the potential complementary role of ⁶⁸Ga-PSMA PET, ⁶⁸Ga-DOTA-RM2 PET and MRI in PCa characterization during the staging phase. A very innovative aspect of the present study relies on the use of PET/MRI scanner for both ⁶⁸Ga-PSMA and ⁶⁸Ga-DOTA-RM2, differently from the few published studies on this topic^7,8. The multitracer approach offers the possibility to identify different sites of disease, thus improving disease characterization and therefore patients' management and follow-up.

Acknowledgements

This research was funded by the Italian Association for Cancer Research (grant IG 2017 Id. 20571) and by the Italian Ministry of Health (PE-2016-02361273); EUDRACT number: 2018-001034-18. Signa PET/MRI system (GEMS, Wakesha, Wisconsin, USA) used in the present work has been purchased with funding from Italian Ministry of Health.