A Systematic Review and Meta-Analysis on the Diagnostic and Prognostic Values of 18F-FDG PET in Uveal Melanoma and Its Hepatic Metastasis.

In this systematic review and meta-analysis (PRISMA-compliant), we tried to investigate diagnostic and prognostic values of 18F-FDG PET in uveal melanoma. A systematic search was conducted on the main medical literature databases to include studies that evaluated 18F-FDG PET as the imaging modality to evaluate patients with uveal melanoma. Overall, 27 studies were included. Twelve had data about the detection rate of 18F-FDG PET in primary intra-ocular tumours. The pooled sensitivity was 45% (95%CI: 41-50%). Furthermore, studies showed that the larger the primary tumour, the higher its uptake. Among the included studies, 13 assessed 18F-FDG PET in detecting metastasis. The pooled sensitivity and specificity were 96% (95%CI: 81-99%) and 100% (95%CI: 94-100%), respectively. Regarding liver metastasis, they were 95% (95%CI: 79-99%) and 100% (95%CI: 91-100%), respectively. Noteworthy, the level of 18F-FDG uptake was a strong predictor of patient survival. Lastly, 18F-FDG PET could characterise lesions from the histopathology perspective, distinguishing high-risk from low-risk diseases. Overall, although not reliable in detecting primary intra-ocular tumours, 18F-FDG PET is highly accurate for diagnosing metastatic uveal melanomas. It can also be a highly valuable modality in terms of patient prognostication. Thus, 18F-FDG PET can be recommended in patients diagnosed with uveal melanoma to enhance decision-making and patient management.

18F-FDG and 68Ga-PSMA PET/CT in Paratesticular Mesothelioma.

ABSTRACT: A 66-year-old man with local prostate adenocarcinoma underwent radical prostatectomy (Gleason score 3 + 4 = 7, pT2c) in 2016. Four years later, he presented with a hydrocele and cystic atypical change in the left scrotum and soft tissue in the left groin. Final histopathology revealed spermatic cord mesothelioma and left hemangiosis carcinomatosa. A bone biopsy of the sacrum revealed infiltrates of a prostatic adenocarcinoma with small cell neuroendocrine differentiation. Dual-tracer PET/CT imaging using 18F-FDG and 68Ga-PSMA was able to identify local recurrence of scrotal mesothelioma and differentiate metastases of prostate cancer from malignant mesothelioma.

Pre-treatment 68 Ga-PSMA-11 PET/CT Prognostic Value in Predicting Response to 177Lu-PSMA-I&T Therapy and Patient Survival.

PURPOSE: To assess the prognostic value of pre-treatment [68Ga]Ga-PSMA-11 PET/CT and other baseline clinical characteristics in predicting prostate cancer (PCa) patients response to [177Lu]Lu-PSMA (PSMA-I&T), as well as patient survival. PROCEDURES: In this retrospective study, 81 patients who received [177Lu]Lu-PSMA-I&T between October 2018 and January 2023 were reviewed. Eligible patients had metastatic castration-resistant PCa, underwent pre-treatment [68Ga]Ga-PSMA-11 PET/CT, and had serum prostate-specific antigen (PSA) levels available. On PET/CT images, SUVmax, SULmax, SUVpeak, and SULpeak of the most-avid tumoral lesion, as well as SUVmean of the parotid gland (P-SUVmean) and liver (L-SUVmean), were measured. Also, whole-body PSMA tumour volume (PSMA-TV) and total lesion PSMA (TL-PSMA) were calculated. To interpret treatment response after [177Lu]Lu-PSMA-I&T, a composite of PSA values and [68Ga]Ga-PSMA-11 PET/CT findings were considered. The outcomes were dichotomised into progressive versus controlled (stable disease or partial response) disease. Then, the association of baseline parameters with patient response was evaluated. Also, survival analyses were performed to assess baseline parameters in predicting overall survival. RESULTS: Sixty patients (age:73 ± 8, PSA:185 ± 371) were included. Patients received at least one cycle of [177Lu]Lu-PSMA therapy (median = 4). Overall, half of the patients showed disease progression. In the progressive versus controlled disease evaluation, the highest SULmax, as well as SUVmax and SULmax to both backgrounds (L-SUVmean and P-SUVmean), were significantly correlated with the outcome (p-values < 0.05). In the multivariate analysis, only SULmax to the L-SUVmean remained significant (p-value = 0.038). The best cut-off was 8 (AUC = 0.71). With a median follow-up of 360 days, 11 mortal events were documented. In the multivariate survival analysis, only SULmax to P-SUVmean (cut-off = 2.4; p-value = 0.043) retained significance (hazard ratio = 4.0). CONCLUSIONS: A greater level of PSMA uptake, specifically higher tumour-to-background uptake in the hottest lesion, may hold substantial prognostic significance, considering both [177Lu]Lu-PSMA-I&T response and patient survival. These ratios may have the potential to be used for PCa patient selection for radioligand therapy.

Application of Artificial Intelligence in Oncologic Molecular PET-Imaging: A Narrative Review on Beyond [18F]F-FDG Tracers Part II. [18F]F-FLT, [18F]F-FET, [11C]C-MET and Other Less-Commonly Used Radiotracers.

Following the previous part of the narrative review on artificial intelligence (AI) applications in positron emission tomography (PET) using tracers rather than 18F-fluorodeoxyglucose ([18F]F-FDG), in this part we review the impact of PET-derived radiomics data on the diagnostic performance of other PET radiotracers, 18F-O-(2-fluoroethyl)-L-tyrosine ([18F]F-FET), 18F-Fluorothymidine ([18F]F-FLT) and 11C-Methionine ([11C]C-MET). [18F]F-FET-PET, using an artificial amino acid taken up into upregulated tumoral cells, showed potential in lesion detection and tumor characterization, especially with its ability to reflect glioma heterogeneity. [18F]F-FET-PET-derived textural features appeared to have the potential to reveal considerable information for accurate delineation for guiding biopsy and treatment, differentiate between low-grade and high-grade glioma and related wild-type genotypes, and distinguish pseudoprogression from true progression. In addition, models built using clinical parameters and [18F]F-FET-PET-derived radiomics features showed acceptable results for survival stratification of glioblastoma patients. [18F]F-FLT-PET-based characteristics also showed potential in evaluating glioma patients, correlating with Ki-67 and patient prognosis. AI-based PET-volumetry using this radiotracer as a proliferation marker also revealed promising preliminary results in terms of guide-targeting bone marrow-preserving adaptive radiation therapy. Similar to [18F]F-FET, the other amino acid tracer which reflects cellular proliferation, [11C]C-MET, has also shown acceptable performance in predicting tumor grade, distinguishing brain tumor recurrence from radiation necrosis, and treatment monitoring by PET-derived radiomics models. In addition, PET-derived radiomics features of various radiotracers such as [18F]F-DOPA, [18F]F-FACBC, [18F]F-NaF, [68Ga]Ga-CXCR-4 and [18F]F-FMISO may also provide useful information for tumor characterization and predict of disease outcome. In conclusion, AI using tracers beyond [18F]F-FDG could improve the diagnostic performance of PET-imaging for specific indications and help clinicians in their daily routine by providing features that are often not detectable by the naked eye.

SPECT/CT, PET/CT, and PET/MRI for Response Assessment of Bone Metastases.

Recent developments in hybrid SPECT/CT systems and the use of cadmium-zinc-telluride (CZT) detectors have improved the diagnostic accuracy of bone scintigraphy. These advancements have paved the way for novel quantitative approaches to accurate and reproducible treatment monitoring of bone metastases. PET/CT imaging using [18F]F-FDG and [18F]F-NaF have shown promising clinical utility in bone metastases assessment and monitoring response to therapy and prediction of treatment response in a broad range of malignancies. Additionally, specific tumor-targeting tracers like [99mTc]Tc-PSMA, [68Ga]Ga-PSMA, or [11C]C- or [18F]F-Choline revealed high diagnostic performance for early assessment and prognostication of bone metastases, particularly in prostate cancer. PET/MRI appears highly accurate imaging modality, but has associated limitations notably, limited availability, more complex logistics and high installation costs. Advances in artificial intelligence (Al) seem to improve the accuracy of imaging modalities and provide an assistant role in the evaluation of treatment response of bone metastases.

Diagnostic Performance of [18F]F-FDG Positron Emission Tomography (PET) in Non-Ophthalmic Malignant Melanoma: A Systematic Review and Meta-Analysis of More Than 10,000 Melanoma Patients.

We described the diagnostic performance of [18F]F-FDG-PET in malignant melanoma by conducting a comprehensive systematic review and meta-analysis of the existing literature. The study was designed following PRISMA-DTA. Original articles with adequate crude data for meta-analytic calculations that evaluated [18F]F-FDG-PET and compared it with a valid reference standard were considered eligible. The pooled measurements were calculated based on the data level (patient/lesion-based). Regarding sub-groups, diagnostic performances were calculated for local, regional and distant involvement. The bivariate model was employed to calculate sensitivity and specificity. The initial search resulted in 6678 studies. Finally, 100 entered the meta-analysis, containing 82 patient-based (10,403 patients) and 32 lesion-based (6188 lesions) datasets. At patient level, overall, [18F]F-FDG-PET had pooled sensitivity and specificity of 81% (95%CI: 73-87%) and 92% (95%CI: 90-94%), respectively. To detect regional lymph node metastasis, the pooled sensitivity and specificity were 56% (95%CI: 40-72%) and 97% (95%CI: 94-99%), respectively. To detect distant metastasis, they were 88% (95%CI: 81-93%) and 94% (95%CI: 91-96%), respectively. At lesion level, [18F]F-FDG-PET had a pooled sensitivity and specificity of 70% (95%CI: 57-80%) and 94% (95%CI: 88-97%), respectively. Thus, [18F]F-FDG-PET is a valuable diagnostic modality for melanoma assessment. It was accurate in various clinical scenarios. However, despite its high specificity, it showed low sensitivity in detecting regional lymph node metastasis and could not replace lymph node biopsy.

Bone Metastasis in Prostate Cancer: Bone Scan Versus PET Imaging.

Prostate cancer is the second most common cause of malignancy among men, with bone metastasis being a significant source of morbidity and mortality in advanced cases. Detecting and treating bone metastasis at an early stage is crucial to improve the quality of life and survival of prostate cancer patients. This objective strongly relies on imaging studies. While CT and MRI have their specific utilities, they also possess certain drawbacks. Bone scintigraphy, although cost-effective and widely available, presents high false-positive rates. The emergence of PET/CT and PET/MRI, with their ability to overcome the limitations of standard imaging methods, offers promising alternatives for the detection of bone metastasis. Various radiotracers targeting cell division activity or cancer-specific membrane proteins, as well as bone seeking agents, have been developed and tested. The use of positron-emitting isotopes such as fluorine-18 and gallium-68 for labeling allows for a reduced radiation dose and unaffected biological properties. Furthermore, the integration of artificial intelligence (AI) and radiomics techniques in medical imaging has shown significant advancements in reducing interobserver variability, improving accuracy, and saving time. This article provides an overview of the advantages and limitations of bone scan using SPECT and SPECT/CT and PET imaging methods with different radiopharmaceuticals and highlights recent developments in hybrid scanners, AI, and radiomics for the identification of prostate cancer bone metastasis using molecular imaging.

Application of Artificial Intelligence in Oncologic Molecular PET-Imaging: A Narrative Review on Beyond [18F]F-FDG Tracers - Part I. PSMA, Choline, and DOTA Radiotracers.

Artificial intelligence (AI) has evolved significantly in the past few decades. This thriving trend has also been seen in medicine in recent years, particularly in the field of imaging. Machine learning (ML), deep learning (DL), and their methods (eg, SVM, CNN), as well as radiomics, are the terminologies that have been introduced to this field and, to some extent, become familiar to the expert clinicians. PET is one of the modalities that has been enhanced via these state-of-the-art algorithms. This robust imaging technique further merged with anatomical modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), to provide reliable hybrid modalities, PET/CT and PET/MRI. Applying AI-based algorithms on the different components (PET, CT, and MRI) has resulted in promising results, maximizing the value of PET imaging. However, [18F]F-FDG, the most commonly utilized tracer in molecular imaging, has been mainly in the spotlight. Thus, we aimed to look into the less discussed tracers in this review, moving beyond [18F]F-FDG. The novel non-[18F]F-FDG agents also showed to be valuable in various clinical tasks, including lesion detection and tumor characterization, accurate delineation, and prognostic impact. Regarding prostate patients, PSMA-based models were highly accurate in determining tumoral lesions' location and delineating them, particularly within the prostate gland. However, they also could assess whole-body images to detect extra-prostatic lesions in a patient automatically. Considering the prognostic value of prostate-specific membrane antigen (PSMA) PET using AI, it could predict response to treatment and patient survival, which are crucial in patient management. Choline imaging, another non-[18F]F-FDG tracer, similarly showed acceptable results that may be of benefit in the clinic, though the current evidence is significantly more limited than PSMA. Lastly, different subtypes of DOTA ligands were found to be valuable. They could diagnose tumoral lesions in challenging sites and even predict histopathology grade, being a highly advantageous noninvasive tool. In conclusion, the current limited investigations have shown promising results, leading us to a bright future for AI in molecular imaging beyond [18F]F-FDG.

Impact of [18F]FDG PET/CT in the Assessment of Immunotherapy-Induced Arterial Wall Inflammation in Melanoma Patients Receiving Immune Checkpoint Inhibitors.

We aimed to investigate the role of [18F]FDG positron emission tomography/computed tomography (PET/CT) in the early detection of arterial wall inflammation (AWI) in melanoma patients receiving immune checkpoint inhibitors (ICIs). Our retrospective study enrolled 95 melanoma patients who had received ICIs. Inclusion criteria were ICI therapy for at least six months and at least three [18F]FDG PET/CTs, including one pretreatment session plus two scans three and six months after treatment initiation. AWI was assessed using quantitative and qualitative methods in the subclavian artery, thoracic aorta, and abdominal aorta. We found three patients with AWI visual suspicion in the baseline scan, which increased to five in the second and twelve in the third session. Most of these patients' treatments were terminated due to either immune-related adverse events (irAEs) or disease progression. In the overall population, the ratio of arterial-wall maximum standardized uptake value (SUVmax)/liver-SUVmax was significantly higher three months after treatment than the pretreatment scan in the thoracic aorta (0.83 ± 0.12 vs. 0.79 ± 0.10; p-value = 0.01) and subclavian artery (0.67 ± 0.13 vs. 0.63 ± 0.12; p-value = 0.01), and it remained steady in the six-month follow-up. None of our patients were diagnosed with definite clinical vasculitis on the dermatology follow-up reports. To conclude, our study showed [18F]FDG PET/CT's potential to visualise immunotherapy-induced subclinical inflammation in large vessels. This may lead to more accurate prediction of irAEs and better patient management.

Predictive value and accuracy of [18F]FDG PET/CT modified response criteria for checkpoint immunotherapy in patients with advanced melanoma.

PURPOSE: Immune checkpoint inhibitors (ICIs) are widely used in metastatic melanoma and dramatically alter the treatment of these patients. Given the high cost and potential toxicity, a reliable method for evaluating treatment response is needed. In this study, we assessed tumor response in patients with metastatic melanoma treated with ICIs using three modified response criteria: PET Response Evaluation Criteria for Immunotherapy (PERCIMT), PET Response Criteria in Solid Tumors for up to Five Lesions (PERCIST5), and immunotherapy-modified PET Response Criteria in Solid Tumors for up to Five Lesions (imPERCIST5). METHODS: Ninety-one patients with non-resectable stage IV metastatic melanoma who received ICIs were retrospectively enrolled in this study. Each patient had two [18F]FDG PET/CT scans performed before and after ICI therapy. Responses at the follow-up scan were evaluated according to PERCIMT, PERCIST5, and imPERCIST5 criteria. Patients were classified into four groups: complete metabolic response (CMR), partial metabolic response (PMR), progressive metabolic disease (PMD), and stable metabolic disease (SMD). To assess the "disease control rate," two groups have been defined based on each criterion: patients with CMR, PMR, and SMD as "disease-controlled group (i.e., responders)" and PMD as the "uncontrolled-disease group (i.e., non-responders)". The correspondence between metabolic tumor response defined by these criteria and clinical outcome was assessed and compared. RESULTS: The response and the disease control rates were 40.7% and 71.4%, 41.8% and 50.5%, and 54.9% and 74.7% based on the PERCIMT, PERCIST5, and imPERCIST5 criteria, respectively. PERCIMT and imPERCIST5 showed significantly different disease control rates from that of PERCIST5 (P < 0.001), whereas it was not significant between PERCIMT and imPERCIST5. Overall survival was significantly longer in the metabolic responder groups than in the non-responder groups based on PERCIMT and PERCIST5 criteria (PERCIMT: 2.48 versus 1.47 years, P = 0.003; PERCIST5: 2.57 versus 1.81 years. P = 0.017). However, according to imPERCIST5 criterion, this difference was not observed (P = 0.12). CONCLUSION: Although the appearance of new lesions can be secondary to an inflammatory response to ICIs and indicative of pseudoprogression, given the higher rate of true progression, the appearance of new lesions should be interpreted deliberately. Of the three assessed modified criteria, PERCIMT appear to provide more reliable metabolic response assessment that correlates strongly with overall patient survival.

Prognostic value of [18F]FDG PET/CT on treatment response and progression-free survival of gastroesophageal cancer patients undergoing perioperative FLOT chemotherapy.

PURPOSE: To evaluate the prognostic role of [18F]FDG PET/CT metabolic parameters in gastric cancer (GC) and gastroesophageal adenocarcinoma (GEJAC) patients receiving neoadjuvant chemotherapy. METHOD: In this retrospective study, 31 patients with biopsy-proven GC or GEJAC were included between August 2016 and March 2020. [18F]FDG PET/CT was performed before the neoadjuvant chemotherapy. Primary tumours' semi-quantitative metabolic parameters were extracted. All patients received a perioperative FLOT regimen thereafter. Post-chemotherapy [18F]FDG PET/CT was performed in most patients (17/31). All patients underwent surgical resection. Histopathology response to treatment and progression-free survival (PFS) were evaluated. Two-sided p-values < 0.05 were considered statistically significant. RESULTS: Thirty-one patients (mean age = 62 ± 8), including 21 GC and 10 GEJAC patients, were evaluated. 20/31(65%) patients were histopathology responders to neoadjuvant chemotherapy, including twelve complete and eight partial responders. During the median follow-up of 42.0 months, nine patients experienced recurrence. The median PFS was 60(95% CI:32.9-87.1) months. Pre-neoadjuvant chemotherapy SULpeak was significantly correlated with pathological response to treatment (p-value = 0.03;odds ratio = 16.75). In survival analysis, SUVmax (p-value = 0.01;hazard ratio[HR] = 1.55), SUVmean (p-value = 0.04;HR = 2.73), SULpeak (p-value < 0.001;HR = 1.91) and SULmean (p-value = 0.04;HR = 4.22) in the post-neoadjuvant chemotherapy pre-operative [18F]FDG PET/CT showed significant correlation with PFS. Additionally, aspects of staging were significantly correlated with PFS (p-value = 0.01;HR = 2.21). CONCLUSIONS: Pre-neoadjuvant chemotherapy [18F]FDG PET/CT parameters, especially SULpeak, could predict the pathological response to treatment in GC and GEJAC patients. Additionally, in survival analysis, post-chemotherapy metabolic parameters significantly correlated with PFS. Thus, performing [18F]FDG PET/CT before chemotherapy may help to identify patients at risk for inadequate response to perioperative FLOT and, after chemotherapy, may predict clinical outcomes.

Prognostic Value of Baseline 18F-FDG PET/CT to Predict Brain Metastasis Development in Melanoma Patients.

To investigate the value of 18F-FDG-PET/CT in predicting the occurrence of brain metastases in melanoma patients, in this retrospective study 201 consecutive patients with pathology-proven melanoma, between 2008 and 2021, were reviewed. Those who underwent 18F-FDG-PET/CT for initial staging were considered eligible. Baseline assessment included histopathology, 18F-FDG-PET/CT, and brain MRI. Also, all patients had serial follow-ups for diagnosing brain metastasis development. Baseline 18F-FDG-PET/CT parameters were analysed using competing risk regression models to analyze their correlation with the occurrence of brain metastases. Overall, 159 patients entered the study. The median follow-up was six years. Among clinical variables, the initial M-stage and TNM-stage were significantly correlated with brain metastasis. Regarding 18F-FDG-PET/CT parameters, regional metastatic lymph node uptake values, as well as prominent SULmax (pSULmax) and prominent SUVmean (pSUVmean), were significantly correlated with the outcome. Cumulative incidences were 10% (6.3-16%), 31% (24.4-38.9%), and 35.2% (28.5-43.5%) after 1, 5, and 10 years. There were significant correlations between pSULmax (p-value < 0.001) and pSULpeak (p-value < 0.001) and the occurrence of brain metastases. The higher these values, the sooner the patient developed brain metastases. Thus, baseline 18F-FDG-PET/CT may have the potential to predict brain metastasis in melanoma patients. Those with high total metabolic activity should undergo follow-up/complementary evaluations, such as brain MRI.

ImmunoPET: Antibody-Based PET Imaging in Solid Tumors.

Immuno-positron emission tomography (immunoPET) is a molecular imaging modality combining the high sensitivity of PET with the specific targeting ability of monoclonal antibodies. Various radioimmunotracers have been successfully developed to target a broad spectrum of molecules expressed by malignant cells or tumor microenvironments. Only a few are translated into clinical studies and barely into clinical practices. Some drawbacks include slow radioimmunotracer kinetics, high physiologic uptake in lymphoid organs, and heterogeneous activity in tumoral lesions. Measures are taken to overcome the disadvantages, and new tracers are being developed. In this review, we aim to mention the fundamental components of immunoPET imaging, explore the groundbreaking success achieved using this new technique, and review different radioimmunotracers employed in various solid tumors to elaborate on this relatively new imaging modality.

[18F]FDG-PET/CT Radiomics and Artificial Intelligence in Lung Cancer: Technical Aspects and Potential Clinical Applications.

Lung cancer is the second most common cancer and the leading cause of cancer-related death worldwide. Molecular imaging using [18F]fluorodeoxyglucose Positron Emission Tomography and/or Computed Tomography ([18F]FDG-PET/CT) plays an essential role in the diagnosis, evaluation of response to treatment, and prediction of outcomes. The images are evaluated using qualitative and conventional quantitative indices. However, there is far more information embedded in the images, which can be extracted by sophisticated algorithms. Recently, the concept of uncovering and analyzing the invisible data extracted from medical images, called radiomics, is gaining more attention. Currently, [18F]FDG-PET/CT radiomics is growingly evaluated in lung cancer to discover if it enhances the diagnostic performance or implication of [18F]FDG-PET/CT in the management of lung cancer. In this review, we provide a short overview of the technical aspects, as they are discussed in different articles of this special issue. We mainly focus on the diagnostic performance of the [18F]FDG-PET/CT-based radiomics and the role of artificial intelligence in non-small cell lung cancer, impacting the early detection, staging, prediction of tumor subtypes, biomarkers, and patient's outcomes.

Assessment of Treatment Response to Lenvatinib in Thyroid Cancer Monitored by F-18 FDG PET/CT Using PERCIST 1.0, Modified PERCIST and EORTC Criteria-Which One Is Most Suitable?

Background: We aimed to compare the established metabolic response criteria PERCIST and EORTC for their applicability and predictive value in terms of clinical response assessment early after the initiation of lenvatinib therapy in patients with metastatic radioiodine-refractory (RAI) thyroid cancer (TC). Methods: In 25 patients treated with lenvatinib, baseline and 4-month follow-up F-18 FDG PET/CT images were analyzed using PERCIST 1.0, modified PERCIST (using SUVpeak or SUVmax) and EORTC criteria. Two groups were defined: disease control (DC) and progressive disease (PD), which were correlated with PFS and OS. Results: PERCIST, mPERCIST, PERCISTmax and EORTC could be applied in 80%, 80%, 88% and 100% of the patients based on the requirements of lesion assessment criteria, respectively. With PERCIST, mPERCIST, PERCISTmax and EORTC, the patients classified as DC and PD ranged from 65 to 68% and from 32 to 35%, respectively. Patients with DC exhibited a longer median PFS than patients with PD for EORTC (p < 0.014) and for PERCIST and mPERCIST (p = 0.037), respectively. Conclusion: EORTC and the different PERCIST criteria performed equally regarding the identification of patients with PD requiring treatment changes. However, the applicability of PERCIST 1.0 using SULpeak seems restricted due to the significant proportion of small tumor lesions.

Incremental Impact of [68 Ga]Ga-PSMA-11 PET/CT in Primary N and M Staging of Prostate Cancer Prior to Curative-Intent Surgery: a Prospective Clinical Trial in Comparison with mpMRI.

PURPOSE: The main objective of this prospective study was to assess the value of gallium-68 prostate-specific membrane antigen ([68 Ga]Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) in primary N and M staging of intermediate- and high-risk prostate cancer (PCa) patients before planned curative-intent radical prostatectomy (RPE) and extended pelvic lymph node dissection (ePLND). The second objective was to compare the [68 Ga]Ga-PSMA-11 PET/CT findings with standard of care pelvic multi-parametric magnetic resonance imaging (mpMRI) in the detection of locoregional lymph node metastases and intraprostatic prostate cancer. PROCEDURES: A total of 81 patients (mean age: 64.5 years, baseline mean trigger PSA (tPSA) 15.4 ng/ml, ± 15.9) with biopsy proven PCa (24 intermediate- and 57 high risk) scheduled for RPE and ePLND were enrolled in this prospective study. In 52 patients [68 Ga]Ga-PSMA-11 PET/CT, pelvic mpMRI, and RPE with ePLND have been performed. Clinical risk stratification and related biomarkers as well as Gleason score (GS) were recorded. The location of the index lesion (IL) was documented systematically for each modality using a standardized segmentation of the prostate in six segments. Distant bone and lymph node metastasis detected by [68 Ga]Ga-PSMA-11 PET/CT were documented. [68 Ga]Ga-PSMA-11 PET/CT findings were correlated with results of mpMRI and histopathology. A consensus of imaging, clinical and/or follow-up findings were used for determining the distant metastases, which were not verified by histopathology. RESULTS: In the patient cohort who underwent RPE, [68 Ga]Ga-PSMA-11 PET/CT and mpMRI detected the IL in 86.5% and 98.1% of the patients, respectively. The median of the maximum standardized uptake value (SUVmax) in the intraprostatic IL was 12 (range, 4.7-67.8). Intraprostatic IL of the high-risk patients showed significantly higher SUVmax than those in patients with intermediate risk for distant metastases (n = 48; median: 17.84 vs. 8.77; p = 0.02). In total 729 LN were removed by ePLND in 48 patients. The histopathology verified 26 pelvic lymph node metastases (pLNM) in 20.8% (10/48) of the patients, which have been correctly identified in 60% of the patients on [68 Ga]Ga-PSMA-11 PET/CT, and in 50% on mpMRI. All but one pLNM had a maximum diameter below 10 mm. Bone metastases (BM) and distant LNM (dLNM) were found in 17.3% of the patients on [68 Ga]Ga-PSMA-11 PET/CT imaging. 39.0% of the [68 Ga]Ga-PSMA-11 PET-positive BM showed no suspicious morphological correlation on CT. CONCLUSION: [68 Ga]Ga-PSMA-11 PET/CT shows high diagnostic performance for N and M staging of patients with intermediate- and high-risk prostate cancer and seems to be superior to pelvic mpMRI in the detection of locoregional lymph node metastases. A significant correlation was found between SUVmax of the intraprostatic index lesion and risk stratification based on tPSA level and GS. The results of this study emphasize again on the role of metabolic molecular imaging using specific tracers in selected patients, leading to tailored therapy approach.

Prognostic value of 2-[18F]FDG PET-CT in metastatic melanoma patients receiving immunotherapy.

PURPOSE: The 2-fluorodeoxyglucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) is used for the evaluation of response to immunotherapy in malignant melanoma. Here, we evaluated the prognostic value of various metabolic parameters in baseline and different time points after therapy. METHODS: In this retrospective study, 51 metastatic melanoma patients, who had received immunotherapy, were included. Patients with baseline and two follow-up 2-[18F]FDG PET/CT studies (3 and 6 months after therapy) were selected. Multiple metabolic parameters and tumor-to-background ratios (TBRs) were extracted and correlated with OS. RESULTS: The 3- and 5-year OS rates were 49% and 43.1%, respectively. On baseline 2-[18F]FDG PET/CT, only standardized uptake value corrected for lean body mass (SULmax and SULpeak), as well as most of the TBRs were predictive for 3- and 5-year OS rates. Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and most of the TBRs were predictive on both follow-up studies. Also, the changes in values of MTV, TLG and most of the TBRs from the baseline to the 3-month and 6- month follow-up studies were prognostic. On multivariate analysis, all of the most predictive parameters for OS were derived from the 3-month follow-up study. The ratio of TBRmean to the mediastinum was the best factor (cutoff value of 2.15, sensitivity of 88.5% and specificity of 68.0% for 3-year survival). CONCLUSION: Metabolic parameters derived from 2-[18F]FDG PET/CT are valuable tools for the prediction of 3- and 5-year OS rates in metastatic melanoma patients undergoing immunotherapy. The 3-month follow-up 2-[18F]FDG PET/CT is of particular importance in this regard.