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Background: In metastatic breast cancer (MBC), [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) can be used for staging. We evaluated the correlation between BC histopathological characteristics and [18F]FDG uptake in corresponding metastases. Patients and Methods: Patients with non-rapidly progressive MBC of all subtypes prospectively underwent a baseline histological metastasis biopsy and [18F]FDG-PET. Biopsies were assessed for estrogen, progesterone, and human epidermal growth factor receptor 2 (ER, PR, HER2); Ki-67; and histological subtype. [18F]FDG uptake was expressed as maximum standardized uptake value (SUVmax) and results were expressed as geometric means. Results: Of 200 patients, 188 had evaluable metastasis biopsies, and 182 of these contained tumor. HER2 positivity and Ki-67 ≥ 20% were correlated with higher [18F]FDG uptake (estimated geometric mean SUVmax 10.0 and 8.8, respectively; p = 0.0064 and p = 0.014). [18F]FDG uptake was lowest in ER-positive/HER2-negative BC and highest in HER2-positive BC (geometric mean SUVmax 6.8 and 10.0, respectively; p = 0.0058). Although [18F]FDG uptake was lower in invasive lobular carcinoma (n = 31) than invasive carcinoma NST (n = 146) (estimated geometric mean SUVmax 5.8 versus 7.8; p = 0.014), the metastasis detection rate was similar. Conclusions: [18F]FDG-PET is a powerful tool to detect metastases, including invasive lobular carcinoma. Although BC histopathological characteristics are related to [18F]FDG uptake, [18F]FDG-PET and biopsy remain complementary in MBC staging (NCT01957332). [ABSTRACT FROM AUTHOR]

This study aimed to investigate the association between the 68Ga- or 18F-radiolabeled prostate-specific membrane antigen (PSMA) tracer expression, represented by the maximum standardised uptake value (SUVmax) of the dominant intraprostatic lesion, and biochemical recurrence (BCR) in primary prostate cancer (PCa) patients prior to robot-assisted radical prostatectomy (RARP). This was a retrospective, multi-centre cohort study of 446 patients who underwent [68Ga]Ga-PSMA-11 (n = 238) or [18F]DCFPyL (n = 206) Positron Emission Tomography/Computed Tomography (PET/CT) imaging prior to RARP. SUVmax was measured in the dominant intraprostatic PCa lesions. [18F]DCFPyL patients were scanned 60 ([18F]DCFPyL-60; n = 106) or 120 ([18F]DCFPyL-120; n = 120) minutes post-injection of a radiotracer and were analysed separately. To normalise the data, SUVmax was log transformed for further analyses. During a median follow-up of 24 months, 141 (30.4%) patients experienced BCR. Log2SUVmax was a significant predictor for BCR (p < 0.001). In the multivariable analysis accounting for these preoperative variables: initial prostate-specific antigen (PSA), radiologic tumour stage (mT), the biopsy International Society of Urological Pathology grade group (bISUP) and the prostate imaging and reporting data system (PI-RADS), Log2SUVmax was found to be an independent predictor for BCR in [68Ga]Ga-PSMA-11 (HR 1.32, p = 0.04) and [18F]DCFPyL-120 PET/CT scans (HR 1.55, p = 0.04), but not in [18F]DCFPyL-60 ones (HR 0.92, p = 0.72). The PSMA expression of the dominant intraprostatic lesion proved to be an independent predictor for BCR in patients with primary PCa who underwent [68Ga]Ga-PSMA-11 or [18F]DCFPyL-120 PET/CT scans, but not in those who underwent [18F]DCFPyL-60 PET/CT scans. [ABSTRACT FROM AUTHOR]

Simple Summary: This meta-analysis provides a first head-to-head comparison of PET and perfusion weighted magnetic resonance imaging (PWI) in the surveillance of post-treatment gliomas in order to distinguish tumor progression (TP) from treatment-related abnormalities (TRA). Although various reviews have been published on the use of either PET or PWI in this setting, no meta-analysis to date provides a head-to-head comparison of both techniques. The findings of this paper illuminate the strengths and limitations of each technique and enable clinicians to take more evidence-based decisions in their daily practice with regard to the imaging surveillance of gliomas. The post-treatment imaging surveillance of gliomas is challenged by distinguishing tumor progression (TP) from treatment-related abnormalities (TRA). Sophisticated imaging techniques, such as perfusion-weighted magnetic resonance imaging (MRI PWI) and positron-emission tomography (PET) with a variety of radiotracers, have been suggested as being more reliable than standard imaging for distinguishing TP from TRA. However, it remains unclear if any technique holds diagnostic superiority. This meta-analysis provides a head-to-head comparison of the diagnostic accuracy of the aforementioned imaging techniques. Systematic literature searches on the use of PWI and PET imaging techniques were carried out in PubMed, Embase, the Cochrane Library, ClinicalTrials.gov and the reference lists of relevant papers. After the extraction of data on imaging technique specifications and diagnostic accuracy, a meta-analysis was carried out. The quality of the included papers was assessed using the QUADAS-2 checklist. Nineteen articles, totaling 697 treated patients with glioma (431 males; mean age ± standard deviation 50.5 ± 5.1 years) were included. The investigated PWI techniques included dynamic susceptibility contrast (DSC), dynamic contrast enhancement (DCE) and arterial spin labeling (ASL). The PET-tracers studied concerned [S-methyl-11C]methionine, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) and 6-[18F]-fluoro-3,4-dihydroxy-L-phenylalanine ([18F]FDOPA). The meta-analysis of all data showed no diagnostic superior imaging technique. The included literature showed a low risk of bias. As no technique was found to be diagnostically superior, the local level of expertise is hypothesized to be the most important factor for diagnostically accurate results in post-treatment glioma patients regarding the distinction of TRA from TP. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate-specific membrane antigen (PSMA)-targeted PET/CT imaging is increasingly being used for (re)staging in prostate cancer. Although PSMA suggests specificity to prostate cancer, previous preclinical studies and case reports have shown this protein to be overexpressed by multiple other tumor types. This study aims to investigate the applicability of a PSMA-targeted PET/CT tracer to detect gastrointestinal cancers, including colon, pancreatic and gastric cancer. Current imaging modalities frequently misjudge disease stage in colorectal, gastric and pancreatic cancer. As treatment decisions are dependent on disease stage, incorrect staging has serious consequences. Previous preclinical research and case reports indicate that prostate-specific membrane antigen (PSMA)-targeted PET/CT imaging might provide a solution to some of these challenges. This prospective clinical study aims to assess the feasibility of [18F]DCFPyL PET/CT imaging to target and visualize primary colon, gastric and pancreatic cancer. In this prospective clinical trial, patients with colon, gastric and pancreatic cancer were included and underwent both [18F]DCFPyL and [18F]FDG PET/CT scans prior to surgical resection or (for gastric cancer) neoadjuvant therapy. Semiquantitative analysis of immunohistochemical PSMA staining was performed on the surgical resection specimens, and the results were correlated to imaging parameters. The results of this study demonstrate detection of the primary tumor by [18F]DCFPyL PET/CT in 7 out of 10 patients with colon, gastric and pancreatic cancer, with a mean tumor-to-blood pool ratio (TBR) of 3.3 and mean SUVmax of 3.6. However, due to the high surrounding uptake, visual distinction of these tumors was difficult, and the SUVmax and TBR on [18F]FDG PET/CT were significantly higher than on [18F]DCFPyL PET/CT. In addition, no correlation between PSMA expression in the resection specimen and SUVmax on [18F]DCFPyL PET/CT was found. In conclusion, the detection of several gastrointestinal cancers using [18F]DCFPyL PET/CT is feasible. However, low tumor expression and high uptake physiologically in organs/background hamper the clear distinction of the tumor. As a result, [18F]FDG PET/CT was superior in detecting colon, gastric and pancreatic cancers. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the most common malignancy in men of middle and older age. The standard treatment strategy for PCa ranges from active surveillance in low-grade, localized PCa to radical prostatectomy, external beam radiation therapy, hormonal treatment and chemotherapy. Recently, the use of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) for metastatic castration-resistant PCa has been approved. PSMA is predominantly, but not exclusively, expressed on PCa cells. Because of its high expression in PCa, PSMA is a promising target for diagnostics and therapy. To understand the currently used RLT, knowledge about pharmacokinetics (PK) and pharmacodynamics (PD) of the PSMA ligand and the PSMA protein itself is crucial. PK and PD properties of the ligand and its target determine the duration and extent of the effect. Knowledge on the concentration–time profile, the target affinity and target abundance may help to predict the effect of RLT. Increased specific binding of radioligands to PSMA on PCa cells may be associated with better treatment response, where nonspecific binding may increase the risk of toxicity in healthy organs. Optimization of the radioligand, as well as synergistic effects of concomitant agents and an improved dosing strategy, may lead to more individualized treatment and better overall survival. [ABSTRACT FROM AUTHOR]

(1) Background: Up to 50% of patients with colorectal cancer either have synchronous colorectal liver metastases (CRLM) or develop CRLM over the course of their disease. Surgery and thermal ablation are the most common local treatment options of choice. Despite development and improvement in local treatment options, (local) recurrence remains a significant clinical problem. Many different imaging modalities can be used in the follow-up after treatment of CRLM, lacking evidence-based international consensus on the modality of choice. In this systematic review, we evaluated 18F-FDG-PET-CT performance after surgical resection, thermal ablation, radioembolization, and neoadjuvant and palliative chemotherapy based on current published literature. (2) Methods: A systematic literature search was performed on the PubMed database. (3) Results: A total of 31 original articles were included in the analysis. Only one suitable study was found describing the role of 18F-FDG-PET-CT after surgery, which makes it hard to draw a firm conclusion. 18F-FDG-PET-CT showed to be of additional value in the follow-up after thermal ablation, palliative chemotherapy, and radioembolization. 18F-FDG-PET-CT was found to be a poor to moderate predictor of pathologic response after neoadjuvant chemotherapy. (4) Conclusions: 18F-FDG-PET-CT is superior to conventional morphological imaging modalities in the early detection of residual disease after thermal ablation and in the treatment evaluation and prediction of prognosis during palliative chemotherapy and after radioembolization, and 18F-FDG-PET-CT could be considered in selected cases after neoadjuvant chemotherapy and surgical resection. [ABSTRACT FROM AUTHOR]

Simple Summary: Imaging plays a crucial role in the accurate staging of prostate cancer. Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer cells, and targeting the PSMA protein for diagnostic purposes has become of great clinical value. Another valuable feature of PSMA is its opportunity to serve as a target for delivering radionuclide therapy to cancer cells. PSMA-ligands can be labeled with various radionuclides, such as alpha and beta-emitters. This review offers an overview of the literature on recent developments in nuclear medicine regarding PSMA in prostate cancer diagnostics and targeted radionuclide therapy. Targeting the prostate-specific membrane antigen (PSMA) protein has become of great clinical value in prostate cancer (PCa) care. PSMA positron emission tomography/computed tomography (PET/CT) is increasingly used in initial staging and restaging at biochemical recurrence in patients with PCa, where it has shown superior detection rates compared to previous imaging modalities. Apart from targeting PSMA for diagnostic purposes, there is a growing interest in developing ligands to target the PSMA-protein for radioligand therapy (RLT). PSMA-based RLT is a novel treatment that couples a PSMA-antibody to (alpha or beta-emitting) radionuclide, such as Lutetium-177 (177Lu), to deliver high radiation doses to tumor cells locally. Treatment with 177Lu-PSMA RLT has demonstrated a superior overall survival rate within randomized clinical trials as compared to routine clinical care in patients with metastatic castration-resistant prostate cancer (mCRPC). The current review provides an overview of the literature regarding recent developments in nuclear medicine related to PSMA-targeted PET imaging and Theranostics. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, mainly due to difficulty in early detection of the disease by current imaging modalities. In this review, we discuss the more specific diagnostic imaging modality that evaluates the presence of specific tumour tracers via positron emission tomography. In addition, we review the available therapeutic applications of these tumour-specific tracers. Pancreatic ductal adenocarcinoma (PDAC) has an inauspicious prognosis, mainly due to difficulty in early detection of the disease by the current imaging modalities. The upcoming development of tumour-specific tracers provides an alternative solution for more accurate diagnostic imaging techniques for staging and therapy response monitoring. The future goal to strive for, in a patient with PDAC, should definitely be first to receive a diagnostic dose of an antibody labelled with a radionuclide and to subsequently receive a therapeutic dose of the same labelled antibody with curative intent. In the first part of this paper, we summarise the available evidence on tumour-targeted diagnostic tracers for molecular positron emission tomography (PET) imaging that have been tested in humans, together with their clinical indications. Tracers such as radiolabelled prostate-specific membrane antigen (PSMA)—in particular, 18F-labelled PSMA—already validated and successfully implemented in clinical practice for prostate cancer, also seem promising for PDAC. In the second part, we discuss the theranostic applications of these tumour-specific tracers. Although targeted radionuclide therapy is still in its infancy, lessons can already be learned from early publications focusing on dose fractioning and adding a radiosensitiser, such as gemcitabine. [ABSTRACT FROM AUTHOR]

Positron emission tomography using [18F]fluorodeoxyglucose (FDG PET) potentially underperforms for staging of patients with grade 1–2 estrogen receptor positive (ER+) breast cancer. The aim of this study was to retrospectively investigate the diagnostic accuracy of FDG PET in this patient population. Suspect tumor lesions detected on conventional imaging and FDG PET were confirmed with pathology or follow up. PET-positive lesions were (semi)quantified with standardized uptake values (SUV) and these were correlated with various pathological features, including the histological subtype. Pre-operative imaging detected 155 pathologically verified lesions (in 74 patients). A total of 115/155 (74.2%) lesions identified on FDG PET were classified as true positive, i.e., malignant (in 67 patients) and 17/155 (10.8%) lesions as false positive, i.e., benign (in 9 patients); 7/155 (4.5%) as false negative (in 7 patients) and 16/155 (10.3%) as true negative (in 14 patients). FDG PET incorrectly staged 16/70 (22.9%) patients. The FDG uptake correlated with histological subtype, showing higher uptake in ductal carcinoma, compared to lobular carcinoma (p < 0.05). Conclusion: Within this study, FDG PET inadequately staged 22.9% of grade 1–2, ER + BC cases. Incorrect staging can lead to inappropriate treatment choices, potentially affecting survival and quality of life. Prospective studies investigating novel radiotracers are urgently needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic pancreatic ductal adenocarcinoma has a dismal prognosis, and to date no curative treatment options exist. The image guided tumor ablation technique irreversible electroporation (IRE) employs high-voltage electrical pulses through the application of several needle electrodes in and around the tumor in order to induce cell death. IRE ablation of the primary tumor has the ability to reduce pancreatic tumor induced immune suppression while allowing the expansion of tumor specific effector T cells, hereby possibly shifting the pancreatic tumor microenvironment into a more immune permissive state. The addition of immune enhancing therapies to IRE might work synergistically and could potentially induce a clinically significant treatment effect. This study protocol describes the rationale and design of the PANFIRE-III trial that aims to assess the safety of the combination of IRE with IMO-2125 (toll-like receptor 9 ligand) and/or nivolumab in patients with metastatic pancreatic ductal adenocarcinoma. Irreversible electroporation (IRE) is a novel image-guided tumor ablation technique with the ability to generate a window for the establishment of systemic antitumor immunity. IRE transiently alters the tumor's immunosuppressive microenvironment while simultaneously generating antigen release, thereby instigating an adaptive immune response. Combining IRE with immunotherapeutic drugs, i.e., electroimmunotherapy, has synergistic potential and might induce a durable antitumor response. The primary objective of this study is to assess the safety of the combination of IRE with IMO-2125 (a toll-like receptor 9 ligand) and/or nivolumab in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). In this randomized controlled phase I clinical trial, 18 patients with mPDAC pretreated with chemotherapy will be enrolled in one of three study arms: A (control): nivolumab monotherapy; B: percutaneous IRE of the primary tumor followed by nivolumab; or C: intratumoral injection of IMO-2125 followed by percutaneous IRE of the primary tumor and nivolumab. Assessments include contrast enhanced computed tomography (ceCT), 18F-FDG and 18F-BMS-986192 (PD-L1) positron emission tomography (PET)-CT, biopsies of the primary tumor and metastases, peripheral blood samples, and quality of life and pain questionnaires. There is no curative treatment option for patients with mPDAC, and palliative chemotherapy regimens only moderately improve survival. Consequently, there is an urgent need for innovative and radically different treatment approaches. Should electroimmunotherapy establish an effective and durable anti-tumor response, it may ultimately improve PDAC's dismal prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: In cancer treatment, immunotherapy is increasingly becoming important as a component of first-line treatment and has improved the prognosis of patients since its introduction. A large group of patients, however, do not respond to immunotherapy, and predicting a treatment response remains challenging. Furthermore, evaluating a response using conventional computed tomography (CT) scans is not straightforward due to the different mechanism of action of immunotherapy compared to chemotherapy. This review provides an overview of positron emission tomography (PET) in predicting and evaluating treatment response to immunotherapy. In multiple malignancies, checkpoint inhibitor therapy has an established role in the first-line treatment setting. However, only a subset of patients benefit from checkpoint inhibition, and as a result, the field of biomarker research is active. Molecular imaging with the use of positron emission tomography (PET) is one of the biomarkers that is being studied. PET tracers such as conventional 18F-FDG but also PD-(L)1 directed tracers are being evaluated for their predictive power. Furthermore, the use of artificial intelligence is under evaluation for the purpose of response prediction. Response evaluation during checkpoint inhibitor therapy can be challenging due to the different response patterns that can be observed compared to traditional chemotherapy. The additional information provided by PET can potentially be of value to evaluate a response early after the start of treatment and provide the clinician with important information about the efficacy of immunotherapy. Furthermore, the use of PET to stratify between patients with a complete response and those with a residual disease can potentially guide clinicians to identify patients for which immunotherapy can be discontinued and patients for whom the treatment needs to be escalated. This review provides an overview of the use of positron emission tomography (PET) to predict and evaluate treatment response to immunotherapy. [ABSTRACT FROM AUTHOR]

Accurate staging of prostate cancer (PCa) at initial diagnosis and at biochemical recurrence is important to determine prognosis and the optimal treatment strategy. To date, treatment of metastatic PCa has mostly been based on the results of conventional imaging with abdominopelvic computed tomography (CT) and bone scintigraphy. However, these investigations have limited sensitivity and specificity which impairs their ability to accurately identify and quantify the true extent of active disease. Modern imaging modalities, such as those based on the detection of radioactively labeled tracers with combined positron emission tomography/computed tomography (PET/CT) scanning have been developed specifically for the detection of PCa. Novel radiotracers include 18F-sodium fluoride (NaF), 11C-/18F-fluorocholine (FCH), 18F-fluordihydrotestosterone (FDHT), 68Gallium and 18F-radiolabeled prostate-specific membrane antigen (e.g., 68Ga-PSMA-11, 18F-DCFPyL). PET/CT with these tracers outperforms conventional imaging. As a result of this, although their impact on outcome needs to be better defined in appropriate clinical trials, techniques like prostate-specific membrane antigen (PSMA) PET/CT have been rapidly adopted into clinical practice for (re)staging PCa. This review focuses on nuclear imaging for PCa bone metastases, summarizing the literature on conventional imaging (focusing on CT and bone scintigraphy—magnetic resonance imaging is not addressed in this review), highlighting the prognostic importance of high and low volume metastatic disease which serves as a driver for the development of better imaging techniques, and finally discussing modern nuclear imaging with novel radiotracers. [ABSTRACT FROM AUTHOR]