Diagnostic Performance and Clinical Impact of PSMA PET/CT versus mpMRI in Patients with a High Suspicion of Prostate Cancer and Previously Negative Biopsy: A Prospective Trial (PROSPET-BX).

BACKGROUND: This prospective single-arm study is designed to compare in parallel 68Ga-PSMA PET/TRUS (transrectal or transperineal) fusion biopsy ("experimental test") with multiparametric MRI (mpMRI)/TRUS fusion prostate biopsy ("standard test") in men with a high suspicion of prostate cancer (PCa) after at least one negative biopsy. The primary objective was to evaluate the diagnostic performance of 68Ga-PSMA PET/TRUS fusion prostate biopsy in comparison to mpMRI/TRUS fusion prostate biopsy analyzed in parallel. Secondarily, we aimed to determine the relationship between the "experimental test" and the histopathological characteristics of the specimen, along with the clinical utility of the "experimental test" compared to the "standard test." SUMMARY: To test the superiority of 68Ga-PSMA PET/CT compared to mpMRI, we will enroll a minimum cohort of 128 patients. Inclusion criteria comprise: age >18 years; blood PSA level >4.0 ng/mL; free-to-total PSA ratio <20%; progressive rise of PSA levels in two consecutive blood samples despite antibiotics; serum blood tests suspicious for PCa; at least one previous negative biopsy; ASAP and/or high-grade PIN; negative digital rectal examination. All eligible patients will undergo 68Ga-PSMA PET/CT and mpMRI scans within 1 month's distance from each other, followed by biopsy session to be completed within 1 month's distance. Targeted TRUS fusion needle biopsy will be performed for all lesions detected with PET and mpMRI. The total duration of the study is 36 months. KEY MESSAGES: By comparing the "experimental test" and the "standard test" in parallel, we will be able to determine the superior diagnostic performance of 68Ga-PSMA PET/CT over mpMRI in detecting PCa, and in particular clinically significant PCa, in the specific cohort of patients with a high suspicion of PCa who are candidates to re-biopsy. The clinical impact of the "experimental test" will be subsequently analyzed in terms of the number of prostate biopsies that could be spared, time-consuming, patient friendliness, and cost-effectiveness.

68Ga-PSMA Positron Emission Tomography/Computerized Tomography for Primary Diagnosis of Prostate Cancer in Men with Contraindications to or Negative Multiparametric Magnetic Resonance Imaging: A Prospective Observational Study.

PURPOSE: 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography may represent the most promising imaging modality to identify and risk stratify prostate cancer in patients with contraindications to or negative multiparametric magnetic resonance imaging. MATERIALS AND METHODS: In this prospective observational study we analyzed 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography in a select group of patients with persistently elevated prostate specific antigen and/or Prostate Health Index suspicious for prostate cancer, negative digital rectal examination and at least 1 negative biopsy. The cohort comprised men with equivocal multiparametric magnetic resonance imaging (Prostate Imaging-Reporting and Data System, version 2 score of 2 or less), or an absolute or relative contraindication to multiparametric magnetic resonance imaging. Sensitivity, specificity and CIs were calculated compared to histopathology findings. ROC analysis was applied to determine the optimal cutoff values of 68Ga labeled prostate specific membrane antigen uptake to identify clinically significant prostate cancer (Gleason score 7 or greater). RESULTS: A total of 45 patients with a median age of 64 years were referred for 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography between January and August 2017. The 25 patients (55.5%) considered to have positive positron emission tomography results underwent software assisted fusion biopsy. We determined the uptake values of regions of interest, including a median maximum standardized uptake value of 5.34 (range 2.25 to 30.41) and a maximum-to-background standardized uptake value ratio of 1.99 (range 1.06 to 14.42). Mean and median uptake values on 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography (ie the maximum standardized uptake value or the maximum-to-background standardized uptake value ratio) were significantly higher for Gleason score 7 lesions than for Gleason score 6 or benign lesions (p <0.001). On ROC analysis a maximum standardized uptake value of 5.4 and a maximum-to-background standardized uptake value ratio of 2 discriminated clinically relevant prostate cancer with 100% overall sensitivity in each case, and 76% and 88% specificity, respectively. CONCLUSIONS: Our findings support the use of 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography for primary detection of prostate cancer in a specific subset of men.

Molecular imaging of PARP in cancer: state-of-the-art.

INTRODUCTION: Poly-ADP-ribose-polymerase inhibitors (PARPi), which exploit the processes of so-called 'synthetic lethality,' have been successfully implemented in oncological practice. However, not all patients respond to PARPi, and there is an unmet need for noninvasive biomarkers suitable for patient selection and monitoring during PARPi therapy. AREAS COVERED: The first clinical applications of molecular imaging with positron emission tomography/computed tomography (PET/CT) with [18F]-FluorThanatrace ([18F]-FTT) and [18F]-PARPi, highly effective PARP-ligands, in patients with several malignancies (head and neck, ovarian, prostate, and breast cancer) are covered, with a particular focus on its potential for pre-treatment selection and follow-up. EXPERT OPINION: By a search made on the most common database, such as PubMed and Google Scholar in a period from January 2010 and 2023, first clinical evidence suggests that PET/CT with [18F]-FTT and [18F]-PARPi might represent a reliable tool for in vivo imaging and quantification of PARP-1 expression in ovarian, prostate, breast, head, and neck cancer, supporting their potential usefulness for patient selection before PARPi-therapies. In addition, a reduction in [18F]-FTT uptake has been registered after therapy initiation and seems to be correlated with patient outcome after PARPi-based regimens. Further studies are needed to better address the value of PARPI-radiolabeled PET imaging in these clinical settings, especially as it concerns technical features such as optimal scan modality (dynamic vs. static) and timing.

FDG-PET imaging in HIV-infected subjects: relation with therapy and immunovirological variables.

PURPOSE: To characterise tissue sites of immune activation and HIV replication we performed FDG-PET in ART-treated and ART-naive HIV-infected individuals. Specific aims were to establish whether HIV-infected patients can be differentiated on the basis of the detection of specific locations of viral replication, even in the presence of an apparently optimal immunovirological response to ART, and whether these FDG-PET findings can be related to immunovirological variables and AIDS history status. PATIENTS AND METHODS: Patients were divided into five groups as follows: subgroup A1 (full responders, n = 8): current ART treatment, CD4+ T lymphocytes >500/mL, viral load <50 copies/mL; subgroup A2 (full responders, n = 5): same criteria as A-1, but with a previous history of AIDS; subgroup A3 (immunological non responders, n = 5): current ART treatment, viral load <50 copies/mL, low CD4+ T lymphocytes (<200/mL); group B (virological non responders, n = 2): current ART treatment, CD4+ T lymphocytes around 500/mL, viral load >50,000 copies/mL; group C (ART-naïve, n = 5): no current or previous ART treatment, increased viral load. RESULTS: PET images revealed different patterns of FDG uptake. All ART-treated patients with either suppressed (<50 copies/mL; Group A) or high viremia (group B) showed a normal pattern of FDG uptake. On the contrary, the ART-naïve subjects with high viraemia (group C) displayed multiple foci of increased glucose metabolism in the lymph nodes. In the ART-naïve subjects, FDG uptake, apparently related to viraemia level, was observed in the upper torso mainly in the axillary nodes bilaterally in patients with viraemia below 100,000 copies/mL; in those with viraemia higher than 100,000 copies/mL, FDG uptake was also observed in the inguinal lymph nodes. CONCLUSIONS: The emergence, in our study, of a correlation between the percentage of CD8+/CD38+/RO+ T cells (well established markers of progression to AIDS independently of CD4+ T lymphocytes) and positive FDG-PET in ART-naive patients is a novel finding that seems to confer prognostic value on FDG uptake. FDG uptake is strongly associated with response to ART independently of a previous AIDS diagnosis. Notably, no differences were observed between ART-treated subjects classed as immunological responders and those classed as non responders. Data herewith indicate that FDG uptake and immunological variables are unrelated when ART is being administered. This is evidence of the complementarity of immunological and FDG measures. FDG uptake is a sensitive marker of disease state and its relation with CD8+/CD38+/CD45RO+ T cells indicates that it can be considered a marker of disease status. The lack of a correlation between FDG uptake and immunological variables in patients under ART warrants further investigation.