Evaluating response to radium-223 using 68Ga-PSMA PET/CT imaging in patients with metastatic castration-resistant prostate cancer.

AIM: Conventional imaging techniques and prostate-specific antigen (PSA) values are not useful to follow-up patients during Radium-223 treatment. The study aimed to evaluate the predictive value of prostate-specific membrane antigen PSMA PET/CT-based response in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Radium-223 dichloride treatment. MATERIALS AND METHODS: Patients treated with radium-223, having performed two 68Ga-PSMA-11 PET/CT scans (baseline 1 month before treatment initiation and follow-up 2 weeks after the third cycle), were retrospectively evaluated. Visual and quantitative PET image analyses were performed, and patients were dichotomized into progressive (PD) and non-PD according to Response Evaluation Criteria in PSMA­imaging (RECIP1.0) and PSMA-PET Progression criteria (PPP). The primary endpoint was overall survival (OS). Cohen's Kappa (κ) was used to test the agreement between the two criteria. The Cox regression hazard model and Kaplan-Meier method were used for survival analyses. RESULTS: Twenty-eight mCRPC patients were evaluated. Sixteen (43%) and 18 (64%) patients had PD according to RECIP1.0 and PPP, respectively; κ = 0.85 (95% CI 0.65-1.00). After a median follow-up of 16 months (interquartile IQR 9-33), 20 (71%) patients died. Patients with PSMA PD showed a higher risk of death than non-PD according to RECIP1.0 (HR = 2.9; 95% CI 1.14-7.46; p = 0.029) and PPP (HR = 2.8; 95% CI 1.04-7.64; p = 0.042). For both criteria, the median OS was shorter for PD than non-PD (37 vs. 12 months, Log-rank; p < 0.05). The C-index for RECIP1.0 and PPP were almost equal (0.66 and 0.63; respectively). CONCLUSION: This study demonstrated that PSMA-PET/CT imaging is valuable for monitoring radium-223 treatment. Both PSMA PET/CT response criteria (RECIP1.0 and PPP) perform similarly predicting OS at follow-up after three cycles of radium-223. These findings urge further validation in prospective trials.

Unusual Prostate-Specific Membrane Antigen (PSMA) Splenic Uptake in a Patient With Prostate Cancer.

There are many benefits to early detection of prostate cancer, including improved survival rates, less invasive treatment options, and better quality of life. Apart from traditional tests and imaging (including the prostate-specific antigen (PSA) test, digital rectal exam, biopsy, computed tomography (CT), and magnetic resonance imaging (MRI)), an imaging technique called prostate-specific membrane antigen positron emission tomography (PSMA PET) is more specific and sensitive, targeting PSMA expressed by prostate cancer cells on their surface. This case report describes a 62-year-old male with metastatic prostate adenocarcinoma and unusual PSMA uptake in the spleen. Elevated PSA levels and MRI indicated aggressive prostate cancer, confirmed by a Gleason score of 7 from biopsies. A PSMA PET/CT scan showed intense activity in both the prostate and spleen, initially suggesting metastasis. However, further imaging identified the splenic lesion as a benign hemangioma. This case showcases the importance of thorough diagnostic evaluations for distinguishing metastatic disease from benign conditions to ensure accurate diagnosis and appropriate treatment.

Prognostic value of PSMA PET in predicting long-term biochemical control following curative intent treatment for prostate cancer.

INTRODUCTION: The aim of this study is to investigate the prognostic value of 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography (PET) metrics in predicting long-term biochemical failure-free survival (BFFS) following curative intent treatment for prostate cancer. METHODS: We completed a prospective study that followed men who had PSMA PET for staging of newly diagnosed prostate cancer between 2015 and 2017 who went on to have curative intent treatment with radiotherapy (RT) or radical prostatectomy (RP). PSMA PET CT imaging was reported and the intraprostatic maximum standardised uptake value (SUVmax) was recorded. The primary outcome was BFFS. Statistical analysis included descriptive statistics, Cox proportional hazards (PH) models, Kaplan-Meier survival analysis and a regression tree structured method. RESULTS: A total of 183 men were included in the analysis with a median age of 66 years and the majority of patients (55.2%) had ISUP grade 1-3 disease. All patients had PSMA PET staging prior to curative intent treatment with RP (66.1%) or external beam radiotherapy (33.9%). PSMA-avid pelvic nodes were present in 26 patients but were not associated with worse biochemical control. A PSMA SUVmax of the prostate primary greater than the median (>5.6) was associated with a lower BFFS (HR: 4.4, 95% CI 1.42-3.72, P = 0.01). A multivariate Cox model incorporating initial biopsy grade, age and PSMA SUVmax showed that PSMA SUVmax was an independent predictor of BFFS. The RT-structured method identified an optimal threshold of 6.8 for PSMA SUVmax, above which patients with ISUP 1-3 disease had a significantly worse BFFS. CONCLUSION: PSMA SUVmax is a strong predictor of BFFS in patients with non-metastatic prostate cancer who underwent curative intent treatment. Patients with low-risk disease on biopsy (ISUP 1-3) but high PSMA SUVmax may have biochemical failure risk analogous to higher-risk disease (ISUP 4-5). These findings allow for further risk stratification and prognosis of patients with newly diagnosed prostate cancer planned for definitive treatment.

Treatment response assessment in mCRPC: is PSMA-PET/CT going to take the lead?

The assessment of response to therapy in prostate cancer (PCa) patients is an ongoing, open issue. Prostate-specific antigen has limitations, especially in advanced metastatic PCa, which often displays intratumor variability in terms of response to therapy. Conventional imaging (i.e. computerized tomography and bone scan) is of limited use for its low sensitivity and specificity. Positron-emission tomography (PET) with prostate-specific membrane antigen (PSMA) demonstrated higher sensitivity and specificity, and novel PSMA-based criteria have been recently proposed for treatment response, with promising results in different scenarios, from chemotherapy to radioligand therapy. PSMA-based criteria have been found to outperform the current RECIST 1.1 and Prostate Cancer Working Group 3 frameworks in describing the behavior of PCa, precisely assessing tumor phenotypes through molecular-imaging-derived parameters. This review critically explores the current evidence about the role of PSMA PET/computed tomography in the assessment of treatment response.

Prostate-specific membrane antigen PET versus [99mTc]Tc-MDP bone scan for diagnosing bone metastasis in prostate cancer: a head-to-head comparative meta-analysis.

Purpose: To evaluate the diagnostic performance of PSMA PET/CT, including [68Ga]Ga-PSMA-11 and [18F]DCFPyL, in comparison with the [99mTc]Tc-MDP bone scan (BS) in identifying bone metastases among prostate cancer patients. Methods: A search was performed in the PubMed and Embase databases to locate pertinent publications from inception to February 12, 2024. The studies included were those that examined the diagnostic effectiveness of PSMA PET/CT (covering [68Ga]Ga-PSMA-11 and [18F]DCFPyL) compared to [99mTc]Tc-MDP BS in identifying bone metastases among prostate cancer patients. The quality of the selected studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist. Results: The meta-analysis included nine articles involving 702 patients. The sensitivity of PSMA PET/CT was higher compared to [99mTc]Tc-MDP BS (0.98 vs. 0.85, P < 0.01), while the specificity of PSMA PET/CT was also higher than [99mTc]Tc-MDP BS (0.97 vs. 0.70,P < 0.01). In subgroup analysis, the sensitivity of [68Ga]Ga-PSMA-11 PET/CT was higher compared to [99mTc]Tc-MDP BS (0.98 vs. 0.86), while the specificity of [68Ga]Ga-PSMA-11 PET/CT was also higher than [99mTc]Tc-MDP BS (0.98 vs. 0.65). Conclusion: Our meta-analysis demonstrates that PSMA PET/CT exhibits superior sensitivity and specificity in comparison with [99mTc]Tc-MDP BS for identifying bone metastases in prostate cancer patients. Further research with head-to-head design is necessary to validate these results and evaluate the clinical effectiveness of these imaging methods. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier PROSPERO CRD42024545112.

Exophthalmos as the initial presentation of metastatic prostate cancer.

Primary metastatic prostate cancer to the orbit is exceedingly rare. Benign lesions, including meningioma, have demonstrated PSMA expression and can be visualized using PSMA-based PET tracers. We report the findings of 18F-PSMA-1007 PET/CT in a 76-year-old man with progressive confusion and long-standing blindness of the left eye. PET/CT scan revealed increased uptake of PSMA in the orbital and temporal region, and other sites throughout the body. Histopathological examination after biopsy of the left orbit showed adenocarcinoma of the prostate. This case substantiates the diverse clinical and radiological presentations of metastatic prostate cancer and underscores the diagnostic significance of targeted biopsy.

Outstanding increase in tumor-to-background ratio over time allows tumor localization by [89Zr]Zr-PSMA-617 PET/CT in early biochemical recurrence of prostate cancer.

BACKGROUND: Positron emission tomography/computed tomography (PET/CT) using prostate-specific membrane antigen (PSMA)-targeted radiotracers labeled with zirconium-89 (89Zr; half-life ~ 78.41 h) showed promise in localizing biochemical recurrence of prostate cancer (BCR) in pilot studies. METHODS: Retrospective analysis of 38 consecutive men with BCR (median [minimum-maximum] prostate-specific antigen 0.52 (0.12-2.50 ng/mL) undergoing [89Zr]Zr-PSMA-617 PET/CT post-negative [68Ga]Ga-PSMA-11 PET/CT. PET/CT acquisition 1-h, 24-h, and 48-h post-injection of a median (minimum-maximum) [89Zr]Zr-PSMA-617 tracer activity of 123 (84-166) MBq. RESULTS: [89Zr]Zr-PSMA-617 PET/CT detected altogether 57 lesions: 18 local recurrences, 33 lymph node metastases, 6 bone metastases in 30/38 men with BCR (78%) and prior negative conventional PSMA PET/CT. Lesion uptake significantly increased from 1-h to 24-h and, in a majority of cases, from 24-h to 48-h. Tumor-to-background ratios significantly increased over time, with absolute increases of 100 or more. No side effects were noted. After [89Zr]Zr-PSMA-617 PET/CT-based treatment, prostate-specific antigen concentration decreased in all patients, becoming undetectable in a third of patients. LIMITATIONS: retrospective, single center design; infrequent histopathological and imaging verification. CONCLUSION: This large series provides further evidence that [89Zr]Zr-PSMA-617 PET/CT is a beneficial imaging modality to localize early BCR. A remarkable increase in tumor-to-background ratio over time allows localization of tumor unidentified on conventional PSMA PET/CT.

Brain Metastatic Prostate Adenocarcinoma: Avoiding Mistaken Identities.

Brain metastatic carcinoma is a rare occurrence among prostate cancer metastases. 68Gallium prostate-specific membrane antigen PET-CT ([68Ga]PSMA PET/CT) is commonly used for prostate cancer staging and detection of biochemical recurrences. However, various CNS tumors exhibit activity on [68Ga]PSMA PET/CT and may often be included in the differential diagnosis. Herein, we present a case of brain metastatic prostate cancer successfully treated with surgical resection and adjuvant stereotactic Gamma Knife radiosurgery (GKRS) followed by androgen deprivation therapy (ADT) to emphasize the need for histologic confirmation. A 70-year-old male with a history of very high-risk prostatic adenocarcinoma presented with biochemical recurrence following radical prostatectomy and irradiation of the prostatic fossa. [68Ga]PSMA PET/CT and MRI identified a solitary lesion in the left occipital lobe; differential diagnosis included prostate metastasis, meningioma, or a new metastatic primary lesion. The patient underwent surgical resection, and immunohistochemical staining confirmed the lesion as brain metastatic prostate adenocarcinoma. One month after resection, the patient underwent GKRS to the tumor bed and two additional metastases, followed by ADT. Repeated imaging 15 months after GKRS revealed stable posttreatment changes with no evidence of new metastases, thus demonstrating durable, effective local and systemic control. Brain metastatic prostate adenocarcinoma without nodal or osseous metastases is a rare phenomenon. The affinity of [68Ga]PSMA PET/CT for non-prostate histologies such as meningioma introduces uncertainty into the diagnostic process. This case demonstrates the durable local control conferred by GKRS toward these lesions and emphasizes the need for clinical, radiographic, and histopathologic data to identify disease presentations and facilitate appropriate treatment regimens.

Isolated spermatic cord metastasis of prostate cancer after radiotherapy detected with 18F-PSMA PET/CT: a case report and literature review.

We report the case of a 65 year-old male with prostate cancer previously treated with external beam radiotherapy and 2 years of androgen deprivation therapy. His nadir PSA reached undetectable level but gradually increased to 0.89 ng/dL. 18F-PSMA PET/CT demonstrated a PSMA-avid lesion at left spermatic cord. Left groin exploration revealed an 8 mm left vas deferens mass. Mass excision was performed and pathology result showed prostatic adenocarcinoma. The metastatic route is unknown but the possible routes are intraluminal route via ejaculatory duct, hematogenous route and lymphatic route. This case also highlights the role of 18F-PSMA PET/CT to detect a recurrent lesion at an atypical site in biochemical failure patients even at the low PSA level.

Case report: positive pitfalls of PSMA PET/CT: diagnostic challenges in degenerative bone lesions including MODIC type 1.

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is an imaging technique that has demonstrated high sensitivity and specificity in detecting prostate cancer and its metastasis, especially in the bones. This case describes a 60-year-old man who presented for increased prostate-specific antigen (PSA) level and underwent [68Ga]gallium-PSMA-11 PET/CT imaging for better disease assessment. 68Ga-PSMA-11 PET/CT revealed numerous radiotracer-positive lesions in both prostate lobes with associated sclerotic lesions on L4 and L5, but only L5 showed increased radiotracer avidity raising the possibility of metastasis. Magnetic Resonance Imaging (MRI) raises the possibility of aggressive MODIC type 1 lesion vs. infectious/inflammatory process. A biopsy of the radiotracer avid area was performed and showed no evidence of metastasis. The final diagnosis was aggressive MODIC type 1, in keeping with the false positive result of 68Ga-PSMA-11 PET/CT. This example demonstrates the possible limitations of 68Ga-PSMA-11 PET/CT, particularly in detecting bone metastases, and emphasizes the need for cautious interpretation and additional study to improve its diagnostic accuracy. Understanding and resolving these limitations is critical for increasing the accuracy of PSMA PET/CT in prostate cancer management.

PSMA PET/CT patterns of recurrence after mono-brachytherapy in men with low and intermediate prostate cancer and subsequent management.

PURPOSE: Brachytherapy as monotherapy is a recommended treatment option for men with low to intermediate risk prostate cancer. Local recurrence is difficult to identify. This study investigated PSMA PET/CT for recurrence after brachytherapy, as well as their subsequent management when recurrence occurred only within the prostate. METHODS: We performed a retrospective single-center analysis for patients who were treated with brachytherapy as monotherapy for prostate cancer from May 2002 to May 2021 and who underwent a PSMA PET/CT for BCR. We report the findings on PSMA PET/CT, quantitative parameters, as well as the later management of the patients. RESULTS: Forty patients were identified, who underwent PSMA PET/CT to investigate a rising PSA at a median (IQR) of 7 years (3.0-10.8) after initial therapy. Median (IQR) PSA at time of PSMA PET/CT was 6.54 ng/mL (3.9-15.5). On PSMA PET/CT, 20/40 (50%) men had prostate-only recurrence. Of the 20 patients with prostate-only recurrence, 8/20 (40%) had recurrence in a high-dose radiation zone, versus 7/20 (35%) in an under-covered zone. On PSMA PET/CT, recurrence within the prostate had median (IQR) SUVmax 10.4 (5.1-15.7) and volume 2.9 mL (2.0-11.2). Subsequent management of these patients with local recurrence included surveillance followed by ADT (9/20, 45%). For those with surveillance followed by ADT, the mean time before introduction of ADT was 4.1 years (range 1-8 years).

Unveiling the Potential of Prostate-Specific Membrane Antigen for Precision Diagnosis and Therapy of Prostate Cancer: A Radiopharmaceutical Perspective.

Prostate-specific membrane antigen (PSMA) has proven to be an important target for diagnostic imaging in prostate cancer. As PSMA is overexpressed on the surface of prostate cancer cells, numerous targeted PSMA ligands have been developed. The emergence of PSMA targeting based on small molecules, such as the PSMA-11 ligand (or PSMA-HBED-CC), has led to breakthroughs, such as [68Ga]Ga-PSMA-11, for positron emission tomography (PET) imaging of biochemically recurrent or metastatic castration-resistant prostate cancer (mCRPC). In addition, the recent approval of [177Lu]Lu-PSMA-617 for the treatment of adult patients with PSMA-positive mCRPC represents an important milestone in prostate cancer therapy. These advances underscore the growing confidence in the use of PSMA-targeted radiopharmaceuticals for the diagnosis and treatment of prostate cancer patients. PSMA-targeted radiopharmaceuticals have been shown to significantly impact treatment planning and clinical decision-making and facilitate the customisation of treatment regimens.

[18F]AlF-PSMA-11 PET in diagnosing prostate cancer: a head-to-head comparison with [68Ga]Ga-PSMA-11 PET and an exploration of dual-phase scanning.

PURPOSE: To evaluate the physiological distribution and tumour detection ability of [18F]AlF-PSMA-11 positron emission tomography (PET) dual-phase scans in patients with prostate cancer (PCa). METHODS: As a retrospective study, clinical and PET data of PCa patients who underwent dual-phase [18F]AlF-PSMA-11 PET of routine scan (45-50 min) and delayed scan (120 min) from November 2020 to June 2021 were collected, and physiological and pathological regions of interest were quantified to determine the time-dependent maximum standardized uptake value (SUVmax) of [18F]AlF-PSMA-11. Part of the above subjects who underwent [68Ga]Ga-PSMA-11 PET in the following 6 months were included in a head-to-head comparison. The difference with a p-value < 0.05 was defined as statistical significance. Diagnosis accuracy of primary and metastatic lesions was measured referring to the surgical findings, pathology, and follow-up imaging. RESULTS: [68Ga]Ga-PSMA-11 and [18F]AlF-PSMA-11 were of the comparable uptake in glands in head, but the latter was of a significant lower distribution in liver and spleen. For the 25 patients initially diagnosed with prostate cancer and 3 patients with biochemical recurrence after radical surgery, the SUVmax of the primary lesions, lacrimal glands, parotid glands and submandibular glands was higher at 120 min compared to that at 45-50 min, but not a significant difference. SUVmax of the liver, spleen and bladder decreased significantly at 120 min, but the bladder SUVmax remained higher than that of primary lesions. SUVmax of the kidneys and centrum was the same in dual-phase scans. For the 31 primary lesions detected in [18F]AlF-PSMA-11 PET, both the SUVmax of the two phases kept the positive correlation with PSA, Gleason score and initial risk stratification. For the 39 distant metastatic lesions, 94.87% accuracy of routine scan and 100% accuracy of delayed scan were acquired, and 7.14% patients (2/28) benefited from the dual-phase [18F]AlF-PSMA-11 scans that revealed novel information on metastatic lesions compared to the routine scan. CONCLUSION: [18F]AlF-PSMA-11 PET expanded the time window and further decreased metabolic background of [68Ga]Ga-PSMA-11 PET. The dual-phase scan of [18F]AlF-PSMA-11 PET can benefit prostate cancer diagnosis via providing more PSMA-specific information.

Prediction of biochemical recurrence after radical prostatectomy from primary tumour characteristics.

OBJECTIVES: To construct and externally calibrate a predictive model for early biochemical recurrence (BCR) after radical prostatectomy (RP) incorporating clinical and modern imaging characteristics of the primary tumour. PATIENTS AND METHODS: Patients who underwent RP following multiparametric magnetic resonance imaging, prostate biopsy and prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT), from two centres in Australia and the Netherlands. The primary outcome was biochemical recurrence-free survival (BRFS), where BCR was defined as a rising PSA level of ≥0.2 ng/mL or initiation of postoperative treatment per clinician discretion. Proportional hazards models to predict time to event were developed in the Australian sample using relevant pre- and post-surgical parameters and primary tumour maximum standardised uptake value (SUVmax) on diagnostic PSMA-PET/CT. Calibration was assessed in an external dataset from the Netherlands with the same inclusion criteria. RESULTS: Data from 846 patients were used to develop the models. Tumour SUVmax was associated with worse predicted 3-year BRFS for both pre- and post-surgical models. SUVmax change from 4 to 16 lessened the predicted 3-year BRFS from 66% to 42% for a patient aged 65 years with typical pre-surgical parameters (PSA level 8 ng/mL, Prostate Imaging-Reporting and Data System score 4/5 and biopsy Gleason score ≥4 + 5). Considering post-surgical variables, a patient with the same age and PSA level but pathological stage pT3a, RP Gleason score ≥4 + 5 and negative margins, SUVmax change from 4 to 16 lessened the predicted 3-year BRFS from 76% to 61%. Calibration on an external sample (n = 464) showed reasonable performance; however, a tendency to overestimate survival in patients with good prognostic factors was observed. CONCLUSION: Tumour SUVmax on diagnostic PSMA-PET/CT has utility additional to commonly recognised variables for prediction of BRFS after RP.

The impact of integrating PRIMARY score or SUVmax with MRI-based risk models for the detection of clinically significant prostate cancer.

PURPOSE: An MRI-based risk calculator (RC) has been recommended for diagnosing clinically significant prostate cancer (csPCa). PSMA PET/CT can detect lesions that are not visible on MRI, and the addition of PSMA PET/CT to MRI may improve diagnostic performance. The aim of this study was to incorporate the PRIMARY score or SUVmax derived from [68Ga]Ga-PSMA-11 PET/CT into the RC and compare these models with MRI-based RC to assess whether this can further reduce unnecessary biopsies. METHODS: A total of 683 consecutive biopsy-naïve men who underwent both [68Ga]Ga-PSMA-11 PET/CT and MRI before biopsy were temporally divided into a development cohort (n = 552) and a temporal validation cohort (n = 131). Three logistic regression RCs were developed and compared: MRI-RC, MRI-SUVmax-RC and MRI-PRIMARY-RC. Discrimination, calibration, and clinical utility were evaluated. The primary outcome was the clinical utility of the risk calculators for detecting csPCa and reducing the number of negative biopsies. RESULTS: The prevalence of csPCa was 47.5% (262/552) in the development cohort and 41.9% (55/131) in the temporal validation cohort. In the development cohort, the AUC of MRI-PRIMARY-RC was significantly higher than that of MRI-RC (0.924 vs. 0.868, p < 0.001) and MRI-SUVmax-RC (0.924 vs. 0.904, p = 0.002). In the temporal validation cohort, MRI-PRIMARY-RC also showed the best discriminative ability with an AUC of 0.921 (95% CI: 0.873-0.969). Bootstrapped calibration curves revealed that the model fit was acceptable. MRI-PRIMARY-RC exhibited near-perfect calibration within the range of 0-40%. DCA showed that MRI-PRIMARY-RC had the greatest net benefit for detecting csPCa compared with MRI-RC and MRI-SUVmax-RC at a risk threshold of 5-40% for csPCa in both the development and validation cohorts. CONCLUSION: The addition of the PRIMARY score to MRI-based multivariable model improved the accuracy of risk stratification prior to biopsy. Our novel MRI-PRIMARY prediction model is a promising approach for reducing unnecessary biopsies and improving the early detection of csPCa.

PSMA PET improves characterization of dural-based intracranial lesions in patients with metastatic prostate cancer.

PURPOSE: Theranostic approaches combining prostate-specific membrane antigen (PSMA)-PET/CT or PET/MRI with PSMA-targeted radionuclide therapy have improved clinical outcomes in patients with prostate cancer (PCa) especially metastatic castrate resistant prostate cancer. Dural metastases in PCa are rare but can pose a diagnostic challenge, as meningiomas, a more common dural based lesions have been shown to express PSMA. The aim of this study is to compare PSMA PET parameters between brain lesions classified as dural metastases and meningiomas in prostate cancer patients. METHODS: A retrospective analysis of PSMA PET/CT scans in patients with PCa and intracranial lesions was conducted. Brain lesions were categorized as dural metastases or meningiomas based on MRI characteristics, longitudinal follow-up, and histopathological characteristics. Standardized uptake values (SUVmax) of each brain lesion were measured, along with SUV ratio referencing parotid gland (SUVR). SUVs between lesions classified as metastases and meningiomas, respectively, were compared using Mann-Whitney-test. Diagnostic accuracy was evaluated using ROC analysis. RESULTS: 26 male patients (median age: 76.5 years, range: 59-96 years) met inclusion criteria. A total of 44 lesions (7 meningiomas and 37 metastases) were analyzed. Median SUVmax and SUVR were significantly lower in meningiomas compared to metastases (SUVmax: 2.7 vs. 11.5, p = 0.001; SUVR: 0.26 vs. 1.05, p < 0.001). ROC analysis demonstrated AUC 0.903; the optimal cut-off value for SUVR was 0.81 with 81.1 % sensitivity and 100 % specificity. CONCLUSION: PSMA PET has the potential to differentiate meningiomas from dural-based metastases in patients with PCa, which can optimize clinical management and thus improve patient outcomes.

A novel assessment of whole-mount Gleason grading in prostate cancer to identify candidates for radical prostatectomy: a machine learning-based multiomics study.

Purpose: This study aims to assess whole-mount Gleason grading (GG) in prostate cancer (PCa) accurately using a multiomics machine learning (ML) model and to compare its performance with biopsy-proven GG (bxGG) assessment. Materials and Methods: A total of 146 patients with PCa recruited in a pilot study of a prospective clinical trial (NCT02659527) were retrospectively included in the side study, all of whom underwent 68Ga-PSMA-11 integrated positron emission tomography (PET) / magnetic resonance (MR) before radical prostatectomy (RP) between May 2014 and April 2020. To establish a multiomics ML model, we quantified PET radiomics features, pathway-level genomics features from whole exome sequencing, and pathomics features derived from immunohistochemical staining of 11 biomarkers. Based on the multiomics dataset, five ML models were established and validated using 100-fold Monte Carlo cross-validation. Results: Among five ML models, the random forest (RF) model performed best in terms of the area under the curve (AUC). Compared to bxGG assessment alone, the RF model was superior in terms of AUC (0.87 vs 0.75), specificity (0.72 vs 0.61), positive predictive value (0.79 vs 0.75), and accuracy (0.78 vs 0.77) and showed slightly decreased sensitivity (0.83 vs 0.89) and negative predictive value (0.80 vs 0.81). Among the feature categories, bxGG was identified as the most important feature, followed by pathomics, clinical, radiomics and genomics features. The three important individual features were bxGG, PSA staining and one intensity-related radiomics feature. Conclusion: The findings demonstrate a superior assessment of the developed multiomics-based ML model in whole-mount GG compared to the current clinical baseline of bxGG. This enables personalized patient management by identifying high-risk PCa patients for RP.

Unveiling the role of PSMA5 in glioma progression and prognosis.

Glioma is the most aggressive intracranial malignancy and is associated with poor survival rates and limited quality of life, impairing neuropsychological function and cognitive competence in survivors. The Proteasome Subunit Alpha Type-5 (PSMA5) is a multicatalytic proteinase complex that has been linked with tumor progression but is rarely reported in glioma. This study investigates the expression pattern, prognostic characteristics, and potential biological functions of PSMA5 in glioma. PSMA5 was significantly overexpressed in 28 types of cancer when compared to normal tissue. Furthermore, elevated levels of PSMA5 were observed in patients with wild-type isocitrate dehydrogenase 1 and exhibited a positive correlation with tumor grade. It was also found to be a standalone predictor of outcomes in glioma patients. Additionally, inhibiting PSMA5-induced cell cycle arrest may provide a therapeutic option for glioma.

Effect of PSMA PET/CT on the Use of Bone Scintigraphy for Prostate Cancer at a University Hospital System.

We observed at our university-based imaging centers that when prostate-specific membrane antigen (PSMA) PET/CT became available for staging and restaging prostate cancer, the volume of bone scanning on patients with prostate cancer (BS-P) markedly decreased. We aimed to study use patterns of PSMA PET/CT and BS-P at our imaging centers during the 4-y period around U.S. Food and Drug Administration approval of PSMA PET/CT in December 2020. We tested the hypothesis that the rate of decline of BS-P accelerated after U.S. Food and Drug Administration approval, as physicians planned for use of PSMA PET/CT in their patients. Methods: Our clinical report system was searched for BS-P and PSMA PET/CT scans from January 2019 through June 2023. Numbers of scans were tabulated by quarter and year. Quantitative and statistical analyses were performed. Results: Annualized average monthly BS-P peaked at 53.7 scans/mo in 2021 and then decreased over time. There were 552 BS-Ps performed in 2019, 503 in 2020, 614 in 2021, 481 in 2022, and 152 in the first half of 2023. BS-P monthly averages declined by 22% from 2021 to 2022 and by 36% from 2022 to 2023, whereas monthly PSMA PET/CT scan averages increased by 1,416% from 2021 to 2022 and by 69% from 2022 to 2023. There was a significantly greater decline in BS-Ps from 2022 to 2023 than from 2021 to 2022 (36% vs. 22%, P < 0.0001). There were 30 PSMA PET/CT scans performed in 2021, 455 in 2022, and 384 in the first half of 2023. The greatest quarterly increase in these scans (400%) occurred at the outset of PSMA PET/CT implementation in quarter 4 of 2021. In quarter 2 of 2023, the percentage of total studies was higher for PSMA PET/CT than for BS-P (74% vs. 26%, P < 0.0001). Conclusion: At our university-based imaging centers, use of BS-P has declined in correlation with the timing of U.S. Food and Drug Administration approval and implementation of PSMA PET/CT. This study illustrates one instance of workflow changes that occur in the nuclear medicine clinic when new agents are introduced and affect clinical management options.

Cellular Membrane-Derived Nanovesicles Expressing hCD64 for Targeting Prostate Cancer.

Extracellular vesicles are ideal therapeutic potentiators for various diseases. However, they commonly lack targeting capability and are rapidly cleared by phagocytes. This requires appropriate administration at high doses, which can lead to toxic and adverse reactions. To overcome these limitations, we developed bleb nanovesicles containing human Fcγ receptor I (hCD64), known for their strong affinity to monomeric IgG. In this study, we focused on prostate cancer, which has a specific membrane antigen. We have utilized the hCD64-expressing bleb nanovesicles attaching anti-prostate-specific membrane antigen (PSMA) antibodies and confirmed their targeting ability in PSMA-related cell lines and prostate cancer xenograft models. Our findings underscore the promising potential of nanovesicle Fcγ receptor-IgG as a platform for cancer diagnosis and therapy systems, inspiring further research.