Prostate-specific membrane antigen PET/CT for primary staging of prostate cancer is becoming increasingly popular due to simultaneous assessment of whole-body disease burden, with superior sensitivity and specificity for detecting metastases compared to conventional imaging. PSMA PET in combination with multiparametric MRI (mpMRI) improves the sensitivity of assessment of extra-prostatic extension and seminal vesicle invasion compared to mpMRI alone, and may serve as a second line modality for image-guided biopsy in selected patients with negative mpMRI and/or negative primary biopsies. The superior diagnostic accuracy of PSMA PET/CT affects clinical decision-making with a change of clinical management in one-fourth of patients compared to conventional imaging. However, at present, the effect of implementing PSMA PET/CT for primary staging on patient outcomes is not clear, and prospective studies are warranted. There are several PSMA tracers with similar performance and minor individual pharmacokinetic differences such as higher rate of unspecific bone uptake with 18F-PSMA-1007, but on the other hand, lower urinary excretion, which could give an advantage in the detection of local recurrence. Proper training of the reporting physicians and knowledge of the pitfalls of the specific PSMA tracer used is of utmost importance for high-quality reading. We aim to provide an overview of the current literature and an update on the status of PSMA PET/CT for primary staging of prostate cancer.

68Ga-PSMA PET/CT is currently used for detection of prostate cancer including metastases, even at low prostate-specific antigen values. A grown number of reports have shown increased uptake of PSMA in neovessels of nonprostatic malignancies including lung cancer, and recently a case report has demonstrated increased PSMA uptake in colorectal adenocarcinoma. In this case report, we demonstrate increased 68Ga-PMSA uptake on PET/CT in metastases from previously treated colon adenocarcinoma, and it illustrates the importance of histology of suspicious lesions on 68Ga-PSMA PET/CT.

Two, respectively, 72- and 76-year-old men with recently diagnosed high-risk prostate cancer were referred for primary staging with ⁶⁸Ga–prostate-specific membrane antigen (PSMA) PET/CT. In both patients, the PET scans revealed increased ⁶⁸Ga-PSMA uptake in, respectively, 3 and 4 rib fractures, characteristically placed as “pearls on a string.” These cases illustrate important pitfalls when reporting PSMA PET.

Background: Routine prostate-specific membrane antigen (PSMA) positron emission tomography (PET) performed for primary staging or restaging of prostate cancer patients is usually done as a single static image acquisition 60 min after tracer administration. In this study, we employ dynamic whole-body (D-WB) PET imaging to compare the pharmacokinetics of [⁶⁸Ga]Ga-PSMA-11 and [¹⁸F]PSMA-1007 in various tissues and lesions, and to assess whether Patlak parametric images are quantitative and improve lesion detection and image readability. Methods: Twenty male patients with prostate cancer were examined using a D-WB PSMA PET protocol. Ten patients were scanned with [⁶⁸Ga]Ga-PSMA-11 and ten with [¹⁸F]PSMA-1007. Kinetic analyses were made using time-activity curves (TACs) extracted from organs (liver, spleen, bone, and muscle) and lesions. For each patient, three images were produced: SUV + Patlak parametric images (K_i and DV). All images were reviewed visually to compare lesion detection, image readability was quantified using target-to-background ratios (TBR), and Ki and DV values were compared. Results: The two PSMA tracers exhibited markedly different pharmacokinetics in organs: reversible for [⁶⁸Ga]Ga-PSMA-11 and irreversible for [¹⁸F]PSMA-1007. For both tracers, lesions kinetics were best described by an irreversible model. All parametric images were of good visual quality using both radiotracers. In general, Ki images were characterized by reduced vascular signal and increased lesion TBR compared with SUV images. No additional malignant lesions were identified on the parametric images. Conclusion: D-WB PET/CT is feasible for both PSMA tracers allowing for direct reconstruction of parametric Ki images. The use of multiparametric PSMA images increased TBR but did not lead to the detection of more lesions. For quantitative whole-body Ki imaging, [¹⁸F]PSMA-1007 should be preferred over [⁶⁸Ga]Ga-PSMA-11 due to its irreversible kinetics in organs and lesions.

⁶⁸Ga-PSMA PET/CT scan on a 70-year-old man with recently diagnosed prostate cancer revealed a spiculating nodule in the apex of the left lung with intense ⁶⁸Ga-PSMA uptake. The nodule had no pathological ¹⁸F-FDG uptake and turned out to be a primary adenocarcinoma of the lung. Cases with complementary pattern of uptake in ¹⁸F-FDG and ⁶⁸Ga-PSMA in metastatic clear cell renal carcinoma and in well-differentiated hepatocellular carcinoma have previously been reported; however, this case illustrates that this unusual pattern can also be present in primary lung cancer.

The aim of this work was to evaluate ⁸²Rubidium (⁸²Rb) positron emission tomography (PET) / computed tomography (CT) as a diagnostic tool for quantitative tumor blood flow (TBF) imaging in prostate cancer (PCa). Study 1 was performed to evaluate ⁸²Rb as a marker of TBF, using ¹⁵O-H2O-PET as reference method. Study 2 investigated the ability of ⁸²Rb uptake measurements to differentiate between PCa and normal prostate. Methods: Study 1. Nine PCa patients scheduled for radical prostatectomy were included. Prostate multiparametric magnetic resonance imaging (mpMRI) and both cardiac and pelvic ¹⁵O-H2O-PET and ⁸²Rb-PET were performed. PET findings were compared to post-prostatectomy Gleason grade group (GGG). Study 2. Fifteen primary high-risk PCa patients and 12 controls without known prostate disease were included in a clinical drug trial (EudraCT 2016-003185-26). ⁶⁸Ga-prostate specific membrane antigen (PSMA)-PET/CT scans of PCa patients were available. Pelvic ⁸²Rb-PET was performed. Results: Study 1. Both ⁸²Rb K1 and ⁸²Rb standard uptake values (SUV) correlated strongly with ¹⁵O-H2O TBF (rho=0.95, P < 0.001 and rho=0.77, P = 0.015, respectively). ⁸²Rb-SUV and K1 were linearly correlated (r=0.92, P = 0.001). ⁸²Rb-SUV correlated with post-prostatectomy GGG (rho=0.70, P = 0.03). Study 2. ⁸²Rb-SUV in PCa (3.19 ± 0.48) was significantly higher than prostate ⁸²Rb-SUV in healthy controls (1.68 ± 0.37) (P < 0.001), with no overlap between groups. Conclusion: Study 1 shows that ⁸²Rb-PET/CT can be used for TBF quantification, and that TBF can be estimated by simple SUV; and suggests that ⁸²Rb-SUV is associated with post-prostatectomy GGG and, hence, cancer aggressiveness. Study 2 shows that ⁸²Rb-uptake is significantly higher in PCa than in normal prostate tissue with no overlap between cohorts, confirming the primary hypothesis of the clinical trial. Consequently, ⁸²Rb-PET/CT may have potential as a non-invasive tool for evaluation of tumor aggressiveness and monitoring in non-metastatic PCa.