Gallium-68 Prostate-specific Membrane Antigen Research Articles

A CASE REPORT: THE ROLE OF PROSTATE-SPECIFIC MEMBRANE ANTIGEN LABELED THERANOSTIC AGENTS IN THE DIAGNOSIS AND TREATMENT OF PROSTATE CANCER

Aims: Prostate cancer is one of the most prevalent cancers worldwide and sometimes it can be deadly which brings out a high quantity of the prostate specific membrane antigen. Gallium-68 prostate specific membrane antigen PET scan is used to detect primary tumors and metastases of prostate cancer. In addition, Lutetium-177 prostate-specific membrane antigen is used for treatment in some special cases. Our case report aims to show the roles of prostate specific membrane antigen labeled theranostic agents in the diagnosis, staging, and treatment of prostate cancer and evaluate the response to the treatment of metastatic castration-resistant prostate cancer. Case Report: A 78-year-old male patient was admitted to Trakya University Hospital Nuclear Medicine Department with the diagnosis of prostate cancer for cancer staging and treatment. Gallium-68 prostate specific membrane antigen was firstly used to detect any metastases and then to evaluate response to the treatment. Lutetium-177 prostate specific membrane antigen was used for treatment. Conclusion: After 3 cures of Lutetium-177 therapy, the patient underwent Gallium - 68 prostate specific membrane antigen PET which demonstrated regression of the metastatic tumor. There was a decrease in the uptake of Gallium-68 prostate specific membrane antigen in the primary tumor and lymph nodes metastases. Also, bone metastases have been cleared. Hence, Lutetium-177 seems to be a promising treatment modality to treat metastatic prostate cancer.

Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer-Updated Diagnostic Utility, Sensitivity, Specificity, and Distribution of Prostate-specific Membrane Antigen-avid Lesions: A Systematic Review and Meta-analysis.

Accurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment. Gallium-68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has increasingly been utilised globally to assess the local and metastatic burden of prostate cancer, typically in biochemically recurrent or advanced disease. Following our previous meta-analysis, a high-volume series has been reported highlighting the utility of 68Ga-PSMA PET in this setting. To perform a systematic review and meta-analysis to update reported predictors of positive 68Ga-PSMA PET according to prior therapy and proportion of positivity in various anatomical locations with sensitivity and specificity profiles. We performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science databases in July 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality assessment was performed using Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analyses of proportions were performed using a random-effect model. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models. A total of 37 articles including 4790 patients were analysed. For patients with biochemical recurrence, positive 68Ga-PSMA PET scans increased with higher pre-PET prostate-specific antigen (PSA) levels. For PSA categories 0-0.19, 0.2-0.49, 0.5-0.99, 1-1.99, and ≥2ng/ml, the percentages of positive scans were 33%, 45%, 59%, 75%, and 95%, respectively. No significant differences in positivity were noted between Gleason sums ≤7 and ≥8. Significant differences in positivity after biochemical recurrence in the prostate bed were noted between radical prostatectomy (22%) and radiotherapy (52%) patients. On per-node analysis, high sensitivity (75%) and specificity (99%) were observed. Ga-68-PSMA PET improves detection of metastases with biochemical recurrence, particularly at low pre-PET PSA levels of >0.2ng/ml (33%) and 0.2-0.5ng/ml (45%). Ga-68-PSMA-PET produces favourable sensitivity and specificity profiles on meta-analysis of pooled data. This analysis highlights different anatomic patterns of metastatic spread according to PSMA PET in the primary and biochemically recurrent settings. Gallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard of care imaging modalities to improve the detection of metastatic disease in prostate cancer, particularly in the setting of disease recurrence. To date, this imaging modality in the setting of primary staging is controversial, given the paucity of data. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality.

Comparison of percentage free PSA, MRI and GaPSMA PET scan for diagnosing cancer prostate in men with PSA between 4 and 20 ng/ml.

Introduction:We compared the diagnostic accuracy of percentage free prostate-specific antigen (PSA), multiparametric magnetic resonance imaging (mpMRI), and gallium-68 prostate-specific membrane antigen positron emission tomography (Ga-PSMA PET) to detect cancer prostate in men with PSA between 4 and 20 ng/ml in prebiopsy settings.Materials and Methods:This prospective study evaluated men with PSA values between 4 and 20 ng/ml, and all patients underwent percentage free PSA estimation, mpMRI, and Ga-PSMA PET scan, followed by cognitive fusion/registration biopsy along with systematic 12-core biopsy to detect cancer prostate. The diagnostic accuracy of percentage free PSA, mpMRI, and Ga-PSMA PET scan was compared with results of cognitive fusion/registration biopsy.Results:A total of 15 patients were included, of which 11 had an identifiable lesion on imaging and 9 had malignancy on the final histopathology report. The sensitivity, specificity, positive predictive value, negative predictive value (NPV), and diagnostic accuracy of mpMRI were 62.5%, 71.4%, 71.4%, 62.5%, and 66.6%, respectively, and that of Ga-PSMA PET scan were 88.8%, 66.6%, 80%, 80%, and 80%, respectively. The sensitivity of detection of clinically significant cancers for Ga-PSMA was higher (100%) compared to MRI (33.3%). However, Ga-PSMA also detected a greater number of insignificant lesions as compared to MRI.Conclusion:Ga-PSMA PET scan has high NPV and accuracy in predicting presence of cancer and can also be used to direct specific biopsy cores during systematic biopsy.

Pitfalls in Gallium-68 PSMA PET/CT Interpretation-A Pictorial Review.

The novel Gallium-68 prostate-specific membrane antigen (PSMA)-bis [2-hydroxy-5-(carboxyethyl)benzyl] ethylenediamine-diacetic acid positron emission tomography (PET) tracer is increasingly used in the evaluation of prostate cancer, particularly in the detection of recurrent disease. However, PSMA is expressed in nonprostatic tissues, as well as in other pathologic conditions. Here we illustrate such interpretive pitfalls with relevant images that one may encounter while reporting PSMA PET/CT. This study aims to show variation in physiological distribution of PSMA activity and uptake in various benign and neoplastic disorders that may be misinterpreted as prostatic metastatic disease. These pitfalls are illustrated to enhance awareness, aiding a more accurate interpretation of the study. Retrospective database of all (68)Ga PSMA PET/CT was created and reviewed. In total, 1115 PSMA PET/CT studies performed between February 27, 2015, and May 31, 2017, were reviewed. Any unusual uptake of PSMA was documented, described, and followed up. All cases were then subdivided into the following 4 categories: physiological uptake, benign pathological uptake, nonprostatic neoplastic uptake, and miscellaneous uptake. A variety of nonprostatic tissues and lesions, including accessory salivary gland, celiac ganglion, gall bladder, Paget's bone disease, reactive lymph nodes, non–small cell lung cancer, renal cell cancer, and neuroendocrine tumor, were found to show PSMA uptake. PSMA uptake is not prostate-specific and can be taken up physiologically and pathologically in nonprostatic tissue. It is important for reporting physicians to recognize these findings and instigate appropriate investigations when required while avoiding unnecessary procedures in physiological variation.

68Ga]PSMA PET/CT Improves Initial Staging and Management Plan of Patients with High-Risk Prostate Cancer

In this retrospective study, we compared the diagnostic value of 68Gallium prostate-specific membrane antigen positron emission tomography computed tomography ([68Ga]PSMA PET/CT) in primary staging of patients with high-risk prostate cancer (PCa), in comparison to CT, magnetic resonance imaging (MRI), and bone scans, and we explored its overall impact on patients' management plan. Patients with pathological confirmation of PCa with high-risk disease were included in this study. Information on patient demographics, clinical and histopathological findings with Gleason score and initial prostate specific antigen PSA levels, and radiological findings for CT, MRI, bone scan, and [68Ga]PSMA PET/CT were retrieved. We stratified the concordance and discordance of each imaging modality on per-patient and per-lesion-site bases. Twenty-one patients with high-risk disease were included in this study. [68Ga]PSMA PET/CT revealed a significantly higher concordance rate (90%) compared to the concordance rates of bone scan (75%), MRI (73%), and CT (60%). [68Ga]PSMA PET/CT had a similar accuracy to MRI in detecting prostate lesions but a higher accuracy for suspicious pelvic lymph nodes (95.2% vs. 80%). It also superseded CT scan in detecting suspicious pelvic lymph nodes (95.2% vs. 75%) and extra-pelvic lymph nodes (100% vs. 75%), as well as bone lesions via bone scan (100% vs. 62.5%). [68Ga]PSMA PET/CT changed the management in 11 patients (52%). [68Ga]PSMA PET/CT is an invaluable imaging modality in the assessment of primary high-risk PCa with great potential for the detection of lymph node spread and bone metastases that would impact the management plan.

68Ga-PSMA-PET/CT in comparison with 18F-fluoride-PET/CT and whole-body MRI for the detection of bone metastases in patients with prostate cancer: a prospective diagnostic accuracy study.

To determine the diagnostic accuracy of 68gallium prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) in comparison with 18F-fluoride-based PET/CT (NaF-PET/CT) and whole-body magnetic resonance imaging (WB-MRI) for the detection of bone metastases in patients with prostate cancer. Sixty patients with prostate cancer were included in the period May 2016 to June 2017. The participants underwent three scans (index tests) within 30 days: a NaF-PET/CT, a WB-MRI and a PSMA-PET/CT. Experienced specialists assessed the scans. In the absence of a histological reference standard, the final diagnosis was determined as a panel diagnosis. Measures of the diagnostic performances of the index tests were calculated from patient-based dichotomous outcomes (0 or ≥ 1 bone metastasis) and pairwise compared (McNemar test). For each index test, the agreement with the final diagnosis with regard to the number of bone metastases detected (0, 1-5, > 5) and the inter-reader agreement was calculated (kappa coefficients). Fifty-five patients constituted the final study population; 20 patients (36%) were classified as having bone metastatic disease as their final diagnosis. The patient-based diagnostic performances were (sensitivity, specificity, overall accuracy) PSMA-PET/CT (100%, 100%, 100%), NaF-PET/CT (95%, 97%, 96%) and WB-MRI (80%, 83%, 82%). The overall accuracy of PSMA-PET/CT was significantly more favourable compared to WB-MRI (p = 0.004), but not to NaF-PET/CT (p = 0.48). PSMA-PET/CT classified the number of bone metastases reliably compared to the final diagnosis (kappa coefficient 0.97) and with an "almost perfect" inter-reader agreement (kappa coefficient 0.93). The overall accuracy of PSMA-PET/CT was significantly more advantageous compared to WB-MRI, but not to NaF-PET/CT. • PSMA-PET/CT assessed the presence of bone metastases correctly in all 55 patients • PSMA-PET/CT was more advantageous compared to WB-MRI • No difference was found between PSMA-PET/CT and NaF-PET/CT.

Диагностические возможности ПЭТ/КТ 68GA-PSMA для пациентов с рецидивом рака предстательной железы

and aim. Most of the patients with biochemical recurrence after radical prostatectomy undergo salvage radiotherapy without guidance from imaging. In recent years, there has been an increasing role of Gallium-68 prostate specific membrane antigen (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT) imaging in the management of prostate cancer. This study aimed to investigate diagnostic performance of 68Ga-PSMA PET/CT in patients with biochemical recurrence after radical prostatectomy. From 2016 to 2017, 19 prostate cancer patients were evaluated by 68Ga-PSMA PET/CT at the Urology Clinic of S.P Botkin City Clinical Hospital; 17 of them had a biochemical recurrence and needed restaging of the disease. The age, prostate specific antigen (PSA) values, therapy at the time of the study, and maximum standard uptake value (SUVmax) were evaluated. The median age of patients was 65 years (interquartile range (IQR) 58.5-70.5), the median total PSA level was 2.36 ng/mL (IQR 1.5-4.19). In 8 of 17 patients, the PSA values did not exceed 2 ng/ml. The median time after radical prostatectomy was 33.2 months. (IQR 12-54.5). Positive PET/CT sites of recurrence were detected in 15 of 17 patients. Nine patients had only one positive site, and in six patients several positive sites were detected. Four patients with PET/CT positive pelvic lymph nodes and/or retroperitoneal space underwent salvage lymphadenectomy. Histological findings confirmed the presence of malignant growth in 3 out of 4 cases. 68Ga-PSMA PET/CT is an effective tool for the early detection of oligometastatic lesions in recurrent prostate cancer.

Detection of prostate cancer lesions using Gallium-68 PSMA-11 PET in men with biochemical recurrence following radical prostatectomy.

236 Background: Conventional imaging techniques infrequently detect the site of prostate cancer disease in men with biochemical recurrence following radical prostatectomy (RP). We examine the use of Gallium-68 Prostate-Specific Membrane Antigen (PSMA) positron emission tomography (PET) to determine the site of disease recurrence in these men. Methods: We retrospectively reviewed men with persistently detectable prostate specific antigen (PSA) and those with formal biochemical recurrence (PSA ≥ 0.2 ng/mL) following RP who underwent PSMA PET scan under our institution's prospective trials (NCT02918357 & NCT02611882). We assessed the location of detected recurrences, and examined the distribution of recurrence location (prostate bed, pelvic lymph nodes (LN), and extra-pelvic disease) according to PSA at time of PET scan. Results: One hundred and fifty-eight men underwent PSMA PET after RP, 46% of men had previously undergone either adjuvant or salvage radiation therapy. Eleven men (7%) had the scan for persistently detectable PSA < 0.2 and 93% of men had biochemical recurrence. At time of RP, 66% of men had ≥pT3a disease, 40% had positive surgical margins, and 18% had positive lymph nodes. Gleason grade at RP was ≤3+3 in 5% of men, 3+4 in 27%, 4+3 in 32% and ≥4+4 in 36%. Overall, 77% of men had a lesion detectable on PSMA PET. Men with higher PSA at time of scan had a higher prevalence of lesions, with all men PSA > 6.0 having at least one lesion on PSMA PET (Table). Overall, we found extra-pelvic lesions in 44% of all men, and 58% of men with PSA ≥ 1.0. These are areas not typically covered by salvage radiation fields. Conclusions: PSMA PET detects lesions in a high proportion of men with biochemical recurrence following RP, with many lesions outside of the pelvis. This may facilitate more precise targeting of treatment areas for these patients. Clinical trial information: NCT02918357. Clinical trial information: NCT02611882. [Table: see text]

Review of Gallium-68 PSMA PET/CT Imaging in the Management of Prostate Cancer.

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.

Lymphangitic Carcinomatosis From Prostate Cancer Identified With Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography Imaging

Lymphangitic carcinomatosis refers to the rare process of diffuse malignant invasion of the pulmonary lymphatics. We describe the first reported case of lymphangitic carcinomatosis visualized with gallium-68 prostate-specific membrane antigen positron emission tomography and its clinical significance in a 53-year-old man with prostate carcinoma. This case highlights the ability of gallium-68 prostate-specific membrane antigen positron emission tomography for prostate carcinoma characterization and the importance of always considering atypical patterns of metastatic disease.

Pilot study: use of gallium-68 PSMA PET for detection of metastatic lesions in patients with renal tumour

BackgroundIn this study, we prospectively evaluate the diagnostic potential of a gallium-68 (68Ga) prostate-specific membrane antigen (PSMA)-binding ligand and positron emission tomography (PET) in detecting metastatic lesions in patients with renal tumour. The secondary aim was to determine whether the findings would result in the alteration of patient management.ResultsTen patients with renal lesion and potential metastatic disease on conventional imaging were recruited. Patients underwent PSMA PET in addition to standard imaging. Nine patients underwent nephrectomy and 4 patients underwent additional targeted biopsy to provide specimens for histopathological validation. There were 89 pathological lesions on CT, of which 32 were removed or biopsied for histopathological correlation. With PSMA PET, 86 PET avid lesions were identified with 36 samples being available for analysis. Thirty-five of 36 samples were positive for renal cell carcinoma deposits, whilst 1 sample was inconclusive for diagnosis on biopsy. For the histologically confirmed lesions, there were no false-negative PSMA PET lesions; however, CT was false negative in 11. In two patients, surgical strategies were changed based on PSMA PET findings.ConclusionsPSMA PET may potentially have a role in the preoperative staging of advanced renal cell carcinoma as PET detected multiple histologically proven metastatic lesions which were false negative on CT scanning, resulting in change in surgical strategies in some patients. We cautiously support a larger study to confirm these results and to assess the longitudinal impact on patient outcomes.Trial registrationAustralia and New Zealand Clinical Trial Registry (ANZCTR), ACTRN12615000854538.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0231-6) contains supplementary material, which is available to authorized users.

Nuclear Medicine Imaging of Prostate Cancer.

The new tracer Gallium-68 prostate-specific membrane antigen (Ga-68 PSMA) yields new promising options for the PET/CT diagnosis ofprostate cancer (PCa) and its metastases. Toovercome limitations of hybrid imaging, known from the use of choline derivatives, seems to be possible with the use of Ga-68 PSMA for PCa. The benefits of hybrid imaging with Ga-68 PSMA for PCa compared to choline derivatives shall be discussed in this article based on an overview of the current literature. Key Points: • Ga-68 PSMA PET/CT can achieve higher detection rates of PCa lesions than PET/CT performed with choline derivatives• The new tracer Ga-68 PSMA has the advantage of high specificity, independence of PSA-level and low nonspecific tracer uptake in surrounding tissue• The new tracer Ga-68 PSMA seems very suitable for MR-PET diagnostic Citation Format: • Schreiter V, Reimann C, Geisel D et al. Nuclear Medicine Imaging of Prostate Cancer. Fortschr Röntgenstr 2016; 188: 1037 - 1044.

Imaging and cancer survivorship: challenges and changing concepts

The widening gap between cancer incidence and mortality testifies to the increasing success of cancer treatment. For example, in Queensland Australia, there are now more than 7 cancer survivors for each patient newly diagnosed with cancer. These individuals represent a population at risk for recurrent malignancy for whom there is a growing demand for imaging services. Imaging for suspected recurrence may be prompted by symptoms or rising tumour markers, whilst for some tumours, imaging contributes to regular surveillance. The benefits of early detection of recurrence through imaging surveillance need to be balanced against cost, patient anxiety and radiation exposure. A recent study has estimated the absolute risk of second cancer induction resulting from use of radiological examinations in this context to be between 0.1% and 10% [1]. Targeting patients at greatest risk of recurrence would improve the balance between risk and benefit for imaging surveillance and is potentially achievable through the use of prognostic imaging biomarkers derived from imaging procedures performed at staging or post-treatment [2]. Increasingly sophisticated treatments for recurrent disease present further challenges to the use of imaging in cancer survivorship. There are now more therapeutic options for patients with localised disease or recurrence to a few sites (oligometastatic disease). Although well established for hepatic metastases from colorectal cancer, surgical resection of localised recurrence is increasingly adopted for alternative sites of recurrence and for other tumour types. For tumour sites unamenable to surgery, stereotactic body radiotherapy can allow focal delivery of high-dose radiation with single or few fractions with promising local control and overall survival rates [3]. These developments create new questions for imaging. Firstly, should imaging surveillance programmes of asymptomatic cancer survivors be developed to allow identification of the oligometastatic state prior to disseminated disease? The potential benefits of surveillance are highlighted by a study of patterns of distant failure and progression in breast cancer which found oligometastatic disease to be more common amongst asymptomatic patients [4]. Secondly, how can imaging be optimised to distinguish oligometastatic from disseminated disease? Imaging in this context must have high sensitivity and specificity on a lesion-by-lesion basis because an accurate assessment of the number of metastases is required to avoid the morbidity of inappropriate oligometastatic treatment, as well as the possibility of oligometastatic treatment being wrongly withheld due to the presence of benign lesions that are indistinguishable from additional metastases. Hybrid imaging techniques that combine modalities with complementary sensitivity and specificity are likely to offer the greatest opportunities for accurate assessment of oligometastatic disease. Higher accuracy for skeletal metastases can be achieved by diphosphonate SPECT/CT or fluoride PET/CT in place of planar scintigraphy [5] whilst integrated FDG-PET/MRI has the potential to optimise detection of skeletal and hepatic recurrence in a single examination [6,7]. The new PET tracer Gallium-68 Prostate Specific Membrane Antigen demonstrates high accuracy for nodal and skeletal recurrence prostate cancer [8]. Imaging protocols for cancer staging are now well established. Increasing cancer survivorship has created a need to develop equivalent protocols for the diagnosis and assessment of tumour recurrence.