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Over 90% of prostate cancers over-express prostate specific membrane antigen (PSMA) and these tumor cells may be accurately targeted for diagnosis by 68Ga-PSMA-positron emission tomography/computed tomography (68Ga-PSMA-PET/CT) imaging. This novel molecular imaging modality appears clinically to have superseded CT, and appears superior to MR imaging, for the detection of metastatic disease. 68Ga-PSMA PET/CT has the ability to reliably stage prostate cancer at presentation and can help inform an optimal treatment approach. Novel diagnostic applications of 68Ga-PSMA PET/CT include guiding biopsy to improve sampling accuracy, and guiding surgery and radiotherapy. In addition to facilitating the management of metastatic castrate resistant prostate cancer (mCRPC), 68Ga-PSMA can select patients who may benefit from targeted systemic radionuclide therapy. 68Ga-PSMA is the diagnostic positron-emitting theranostic pair with the beta emitter Lutetium-177 PSMA (177Lu-PSMA) and alpha-emitter Actinium-225 PSMA (225Ac-PSMA) which can both be used to treat PSMA-avid metastases of prostate cancer in the molecular tumor-targeted approach of theranostic nuclear oncology.

BackgroundProstate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a promising yet not curative approach in castration-resistant (CR) prostate cancer (PC). Rational combination therapies may improve treatment efficacy. Here, we explored the effect of androgen receptor blockade (ARB) on PSMA expression visualized by PET and its potential additive effect when combined with 177Lu-PSMA RLT in a mouse model of prostate cancer.MethodsMice bearing human CRPC (C4-2 cells) xenografts were treated with 10 mg/kg enzalutamide (ENZ), with 50 mg/kg bicalutamide (BIC), or vehicle (control) for 21 days. PSMA expression was evaluated by 68Ga-PSMA11 PET/CT and quantified by flow cytometry of tumor fine needle aspirations before treatment and on days 23, 29, 34, and 39 post-therapy induction. For the RLT combination approach, mice bearing C4-2 tumors were treated with 10 mg/kg ENZ or vehicle for 21 days before receiving either 15 MBq (84 GBq/μmol) 177Lu-PSMA617 or vehicle. DNA damage was assessed as phospho-γH2A.X foci in tumor biopsies. Reduction of tumor volume on CT and survival were used as study endpoints.ResultsTumor growth was delayed by ARB while 68Ga-PSMA11 uptake increased up to 2.3-fold over time when compared to controls. ABR-induced upregulation of PSMA expression was confirmed by flow cytometry. Phospho-γH2A.X levels increased 1.8- and 3.4-fold at 48 h in response to single treatment ENZ or RLT and ENZ+RLT, respectively. Despite significantly greater DNA damage and persistent increase of PSMA expression at the time of RLT, no additional tumor growth retardation was observed in the ENZ+RLT group (vs. RLT only, p = 0.372 at day 81). Median survival did not improve significantly when ENZ was combined with RLT.ConclusionARB-mediated increases in PSMA expression in PC xenografts were evident by 68Ga-PSMA11 PET imaging and flow cytometry. 177Lu-PSMA617 effectively decreased C4-2 tumor size. However, while pre-treatment with ARB increased DNA damage significantly, it did not result in synergistic effects when combined with RLT.

In this systematic review and meta-analysis, the diagnostic performance of [.sup.68]Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT was compared with that of [.sup.18]F-DCFPyL PET for patients with suspected prostate cancer (PCa). Up to September 2023, the PubMed, Embase and Web of Science databases were thoroughly searched for relevant papers. Studies examining the diagnostic performance of [.sup.18]F-DCFPyL PET and [.sup.68]Ga-PSMA PET/CT in patients with suspected PCa were included in the present review. The Quality Assessment of Diagnostic Performance Studies-2 tool was used to rate the diagnostic performance of each study. The diagnostic performance of [.sup.18]F-DCFPyL PET and [.sup.68]Ga-PSMA PET/CT for primary PCa was examined by 13 studies included, comprising 1,178 patients. The pooled sensitivity and specificity of [.sup.18]F-DCFPyL PET were 0.92 (95% CI, 0.85-0.96) and 0.59 (95% CI, 0.08-0.96), respectively. For [.sup.68]Ga-PSMA PET/CT, the pooled sensitivity and specificity were 0.96 (95% CI, 0.88-0.99) and 0.71 (95% CI, 0.57-0.82), respectively. [.sup.18]F-DCFPyL PET and [.sup.68]Ga-PSMA PET/CT both had an area under the receiver operating characteristic curve of 0.92 (95% CI, 0.89-0.94). In addition, the Fagan nomogram revealed that the post-test probabilities for [.sup.18]F-DCFPyL PET and [.sup.68]Ga-PSMA PET/CT could rise to 69 and 77% when the pre-test probability was set at 50%. In conclusion, a comparable diagnostic performance for patients with suspected PCa was determined for [.sup.18]F-DCFPyL PET and [.sup.68]Ga-PSMA PET/CT. However, it is crucial to keep in mind that the findings of the present meta-analysis come from investigations with modest sample sizes. Therefore, more extensive research is required to obtain more solid data. Key words: [.sup.18]F-DCFPyL PSMA PET, [.sup.68]Ga-PSMA PET/CT, prostate cancer, diagnostic performance, meta-analysis

In this systematic review and meta-analysis, the diagnostic performance of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT was compared with that of 18F-DCFPyL PET for patients with suspected prostate cancer (PCa). Up to September 2023, the PubMed, Embase and Web of Science databases were thoroughly searched for relevant papers. Studies examining the diagnostic performance of 18F-DCFPyL PET and 68Ga-PSMA PET/CT in patients with suspected PCa were included in the present review. The Quality Assessment of Diagnostic Performance Studies-2 tool was used to rate the diagnostic performance of each study. The diagnostic performance of 18F-DCFPyL PET and 68Ga-PSMA PET/CT for primary PCa was examined by 13 studies included, comprising 1,178 patients. The pooled sensitivity and specificity of 18F-DCFPyL PET were 0.92 (95% CI, 0.85-0.96) and 0.59 (95% CI, 0.08-0.96), respectively. For 68Ga-PSMA PET/CT, the pooled sensitivity and specificity were 0.96 (95% CI, 0.88-0.99) and 0.71 (95% CI, 0.57-0.82), respectively. 18F-DCFPyL PET and 68Ga-PSMA PET/CT both had an area under the receiver operating characteristic curve of 0.92 (95% CI, 0.89-0.94). In addition, the Fagan nomogram revealed that the post-test probabilities for 18F-DCFPyL PET and 68Ga-PSMA PET/CT could rise to 69 and 77% when the pre-test probability was set at 50%. In conclusion, a comparable diagnostic performance for patients with suspected PCa was determined for 18F-DCFPyL PET and 68Ga-PSMA PET/CT. However, it is crucial to keep in mind that the findings of the present meta-analysis come from investigations with modest sample sizes. Therefore, more extensive research is required to obtain more solid data.

Although prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is recommended for staging high risk prostate cancer (PCa), recently, it has demonstrated a good accuracy to guide targeted biopsy for the diagnosis of PCa. In this study we evaluated the cost-effectiveness of PSMA PET/CT as single procedure for diagnosis and staging high grade PCa. From June 2022 to June 2025 300 men (median age=65 years) underwent transperineal prostate biopsy at Cannizzaro Hospital (Catania, Italy) for suspicion of high grade PCa (PSA ≥20 ng/ml) and/or suspicious digital rectal examination (DRE). All the patients underwent PSMA PET/CT and intraprostatic lesions with a standard uptake value (SUV ) ≥8 were submitted to targeted biopsies plus extended prostate biopsy. The overall cost of prostate biopsy was calculated using the Italian National Public Health System \"Day Service\" and \"out of pocket\" by market research to evaluate the cost of PSMA PET/CT, multiparametric magnetic resonance image (mpMRI), lung and abdominal CT and bone scan. Median PSA was 29.6 ng/ml (range=20-785 ng/ml) and 135/300 (45%) had positive DRE; a clinically significant PCa was found in 295/300 (98.3%) patients and 270/295 (91.5%) had a Gleason score ≥8/ISUP Grade Group ≥4. Clinical staging by PSMA PET/CT demonstrated: 125 (42.3%) cT2PCa . 170 (57.3%) cT3PCa cases; in detail, 86/295 (29.1%) had positive nodes, 42 (14.2%) bone metastases and 29 (9.8%) multiple metastases. The overall cost of the 300 prostate biopsies calculated using the Day Service model was 57,120€; conversely, the cost \"out of pocket\" of PSMA PET/CT would have been equal to 300,000/450,000€ and its exclusive use would have spared 103,000/300,000€ (25.5-40%) equal to the cost of mpMRI, bone scan, CT and staff trained to perform procedures reducing time of diagnosis and staging from a median of 90 to 45 days. PSMA PET/CT for diagnosis and staging as a single imaging procedure in men with suspicion high grade PCa, improved cost-effectiveness by reducing cost (25.5-40%), time to the diagnosis and staging, whilst allowing for timely therapy initiation in men with high risk of metastases.

Background PSMA PET/CT visualises prostate cancer residual disease or recurrence at lower PSA levels compared to conventional imaging and results in a change of treatment in a remarkable high number of patients. Radiotherapy with dose escalation to the former prostate bed has been associated with improved biochemical recurrence-free survival. Thus, it can be hypothesised that PSMA PET/CT-based radiotherapy might improve the prognosis of these patients. Methods One hundred twenty-nine patients underwent PSMA PET/CT due to biochemical persistence (52%) or recurrence (48%) after radical prostatectomy without evidence of distant metastases (February 2014–May 2017) and received PSMA PET/CT-based radiotherapy. Biochemical recurrence free survival (PSA ≤ 0.2 ng/ml) was defined as the study endpoint. Results Patients with biochemical persistence were significantly more often high-risk patients with significantly shorter time interval before PSMA PET/CT than patients with biochemical recurrence. Patients with biochemical recurrence had significantly more often no evidence of disease or local recurrence only in PSMA PET/CT, whereas patients with biochemical persistence had significantly more often lymph node involvement. Seventy-three patients were started on antiandrogen therapy prior to radiotherapy due to macroscopic disease in PSMA PET/CT. Cumulatively, 70 (66–70.6) Gy was delivered to local macroscopic tumor, 66 (63–66) Gy to the prostate fossa, 61.6 (53.2–66) Gy to PET-positive lymph nodes and 50.4 (45–52.3) Gy to lymphatic pathways. Median PSA after radiotherapy was 0.07 ng/ml with 74% of patients having a PSA ≤ 0.1 ng/ml. After a median follow-up of 20 months, median PSA was 0.07 ng/ml with ongoing antiandrogen therapy in 30 patients. PET-positive patients without antiandrogen therapy at last follow-up (45 patients) had a median PSA of 0.05 ng/ml with 89% of all patients, 94% of patients with biochemical recurrence and 82% of patients with biochemical persistence having a PSA ≤ 0.2 ng/ml. Post-radiotherapy PSA ≤ 0.1 ng/ml and biochemical recurrence vs. persistence were significantly associated with a PSA ≤ 0.2 ng/ml at last follow-up. Conclusions PSMA PET/CT-based radiotherapy is an effective local salvage treatment option with significant PSA response in patients with biochemical recurrence or persistence after radical prostatectomy leading to deferral of long-term ADT or systemic therapy.

Background To determine the potential role of 68 Ga-PSMA positron emission tomography/computed tomography (PET/CT) in radiotherapy (RT) planning for prostate cancer (PCa). Methods One hundred twenty-nine patients (pts) with 68 Ga-PSMA PET/CT were retrospectively analysed. Potentially influencing factors (androgen deprivation therapy, amount of 68 Ga-PSMA-HBED-CC, PSA doubling time ≤/> 10 months, PSA before PET/CT, T−/N-category and Gleason score) were evaluated by logistic regression analysis. The detection rate of PSMA PET/CT was compared to contrast enhanced CT and its impact on RT management analysed. Results One hundred twenty-nine patients (pts) (20 at initial diagnosis, 49 with PSA relapse and 60 with PSA persistence after radical prostatectomy) received PSMA PET/CT prior to RT. The majority of pts. (71.3%) had PET-positive findings (55.1% of pts. with PSA recurrence, 75% of pts. with PSA persistence and 100% of newly diagnosed pts). Median PSA before PET/CT in pts. with pathological findings ( n  = 92) was 1.90 ng/ml and without ( n  = 37) 0.30 ng/ml. PSA level at time of PET/CT was the only factor associated with PET-positivity. In pts. with a PSA ≤ 0.2 ng/ml, the detection rate of any lesion was 33.3%, with a PSA of 0.21–0.5 ng/ml 41.2% and with a PSA of 0.51–1.0 ng/ml 69.2%, respectively. Regarding the anatomic distribution of lesions, 42.2% and 14.7% of pts. with relapse or persistence had pelvic lymph node and distant metastases. In pts. at initial diagnosis the detection rate of pelvic lymph nodes and distant metastases was 20% and 10%. 68 Ga-PSMA PET/CT had a high detection rate of PCa recurrence outside the prostatic fossa in pts. being considered for salvage RT (22.4% PET-positive pelvic lymph nodes and 4.1% distant metastases). Compared to CT, PSMA PET/CT had a significantly higher sensitivity in diagnosing rates of local recurrence/primary tumour (10.1% vs. 38%), lymph nodes (15.5% vs. 38.8%) and distant metastases (5.4% vs. 14.0%). This resulted in a modification of RT treatment in 56.6% of pts. Conclusions The detection of PCa is strongly associated with PSA level at time of 68 Ga-PSMA PET/CT. PSMA PET/CT differentiates between local, regional and distant metastatic disease with implications for disease management. PSMA PET/CT allows for tumour detection in post-prostatectomy pts. with PSA ≤ 0.5 ng/ml considered for salvage RT.

Purpose This study aimed to calculate an applicable relative ratio threshold value instead of the absolute threshold value for simultaneous 68 Ga prostate-specific membrane antigen/positron emission tomography ([ 68 Ga]Ga-PSMA-11 PET) in patients with prostate cancer (PCa). Materials and methods Our study evaluated thirty-two patients and 170 focal prostate lesions. Lesions are classified into groups according to Prostate Imaging Reporting and Data System (PI-RADS). Standardized uptake values maximum (SUVmax), corresponding lesion-to-background ratios (LBRs) of SUVmax, and LBR distributions of each group were measured based on regions of interest (ROI). We examined LBR with receiver operating characteristic analysis to determine threshold values for differentiation between multiparametric magnetic resonance imaging (mpMRI)-positive and mpMRI-negative lesions. Results We analyzed a total of 170 focal prostate lesions. Lesions number of PI-RADS 2 to 5 was 70, 16, 46, and 38. LBR of SUVmax of each PI-RADS scores was 1.5 (0.9, 2.4), 2.5 (1.6, 3.4), 3.7 (2.6, 4.8), and 6.7 (3.5, 12.7). Based on an optimal threshold ratio of 2.5 to be exceeded, lesions could be classified into MRI-positive lesion on [ 68 Ga]Ga-PSMA PET with a sensitivity of 85.2%, a specificity of 72.0%, with the corresponding area under the receiver operating characteristic curve (AUC) of 0.83, p  < 0.001. This value matches the imaging findings better. Conclusion The ratio threshold value of SUVmax, LBR, has improved clinical and research applicability compared with the absolute value of SUVmax. A higher threshold value than the background’s uptake can dovetail the imaging findings on MRI better. It reduces the bias from using absolute background uptake value as the threshold value.

Background/Objectives: The aim of this study was to investigate the relationship between the PRIMARY score derived from [68Ga]Ga-PSMA PET/CT and key clinical and pathological parameters of prostate cancer aggressiveness, including the PSA level, ISUP Grade Group, and D’Amico risk classification, in patients with biopsy-proven prostate cancer. A secondary aim was to evaluate the interobserver agreement of the PRIMARY score in routine clinical practice. Methods: This retrospective analysis included 51 patients with histopathologically confirmed prostate adenocarcinoma who underwent [68Ga]Ga-PSMA PET/CT imaging for staging. PRIMARY scores were determined based on the intraprostatic uptake pattern, intensity, and zonal localization. These scores were compared with PSA levels, ISUP GG, D’Amico risk classification, and histopathological features such as the cribriform pattern, intraductal carcinoma, perineural invasion, extraprostatic extension, and lymphovascular invasion. The PRIMARY scores were independently assigned by a total of three nuclear medicine physicians, and interobserver agreement was calculated using Fleiss’ kappa analysis. Results: Significant associations were found between the PRIMARY scores and the PSA level, ISUP Grade Group, and D’Amico risk classification. The most prevalent score was PRIMARY 5 (54.9%), which was significantly associated with ISUP GG 5 and the high-risk category in D’Amico classification. Among patients with PRIMARY Score 2, a substantial proportion (64.7%) had ISUP GG ≥ 3, and 58.8% were in the high-risk group, highlighting the limitations of binary PRIMARY classification. No statistically significant correlations were found between the PRIMARY scores and specific histopathologic features. Interobserver agreement was excellent (κ = 0.833). Conclusions: The PRIMARY score demonstrates high reproducibility and clinical relevance in stratifying prostate cancer aggressiveness. However, the findings challenge the reliability of binary classifications, particularly for patients with Score 2, who may still harbor high-grade disease. Integrating imaging-based scores with clinical and histopathological data is essential, particularly for accurate staging and decision-making regarding active surveillance.

68 Gallium prostate specific membrane antigen (PSMA) ligand positron emission tomography (PET) is an increasingly used imaging modality in prostate cancer, especially in cases of tumor recurrence after curative intended therapy. Owed to the novelty of the PSMA-targeting tracers, clinical evidence on the value of PSMA-PET is moderate but rapidly increasing. State of the art imaging is pivotal for radiotherapy treatment planning as it may affect dose prescription, target delineation and use of concomitant therapy. This review summarizes the evidence on PSMA-PET imaging from a radiation oncologist’s point of view. Additionally a short survey containing twelve examples of patients and 6 additional questions was performed in seven mayor academic centers with experience in PSMA ligand imaging and the findings are reported here.