Positron Emission Tomography Research Articles (Page 1)

Stress-related neural activity (SNA), as measured by amygdala metabolism, has been linked in prior work to all-cause mortality and major adverse cardiovascular events. In this study, we sought to clarify SNA determinants and test whether age modifies its association with all-cause mortality. Using 2-[18 F]fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET), we quantified amygdala metabolism, a surrogate for SNA, in 1,336 patients (mean age 59.4 ± 15.6 years, 37.8% women). Assessing demographic and imaging confounders, associations between SNA and mortality were evaluated in a subgroup of 960 participants with a median 5-year follow-up (IQR 3-9). Higher SNA appears independently associated with greater all-cause mortality across all age groups (HR 1.45, 95% CI 1.08-1.95; p = 0.012). The association is strongest in younger, healthier individuals (HR 7.86, 95% CI 2.92-21.21; p < 0.001) and attenuates with advancing age. Mediation analysis indicates that SNA accounts for 38.2% (95%CI 15.7%-60.7%) of the age-mortality link. Here, we find that SNA is independently associated with all-cause mortality, with effect sizes that diminish with age; if confirmed, incorporating SNA into risk models alongside conventional factors may improve mortality prediction and help identify younger adults, who appear low risk by standard criteria, for closer follow-up and preventive strategies.

To investigate the clinical relevance of occipital hypoperfusion in Parkinson's disease (PD) with respect to clinical phenotype and risk of dementia conversion. We enrolled 349 patients with newly diagnosed PD and 48 healthy controls who underwent dual-phase 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane (18F-FP-CIT) positron emission tomography (PET). Patients with PD were classified into three groups based on posterior cortical perfusion patterns on early-phase 18F-FP-CIT PET images: PD with preserved posterior cortical perfusion (n = 186), PD with parieto-temporal hypoperfusion (n = 84), and PD with parieto-temporo-occipital hypoperfusion (n = 79). Baseline clinical features and dementia conversion risk were compared across PD groups. Patients with preserved posterior cortical perfusion were younger than those in the other PD groups. The parieto-temporo-occipital hypoperfusion group tended to have lower Cross-Cultural Smell Identification Test scores, a higher prevalence of rapid eye movement sleep behavior disorder, higher Unified PD Rating Scale motor scores, and more severe reductions in striatal dopamine transporter availability than the other groups. The risk of dementia conversion was lower in patients with preserved posterior cortical perfusion than in those with posterior cortical hypoperfusion. However, the risk of dementia conversion did not differ between the parieto-temporal and parieto-temporo-occipital hypoperfusion groups. Additional occipital hypoperfusion was not associated with an imminent risk of dementia conversion in patients with PD with posterior cortical hypoperfusion. Nonetheless, occipital involvement may serve as an indicator of the diffuse malignant subtype of PD.

Carnitine and its acyl derivatives are essential for the transport of fatty acids from the cytosol into the mitochondrial matrix for β-oxidation, which supplies the cell with energy. Altered transport and metabolism of carnitine are associated with multiple diseases and disorders, including heart disease, insulin resistance, and cancer. Fluorinated carnitine derivatives have the potential to measure aberrant carnitine metabolism in these disorders using 19F-NMR and mass spectrometry. Furthermore, by radiolabeling carnitines with fluorine-18, altered carnitine utilisation may be visualised in vivo using positron emission tomography (PET) imaging. Here, the design and synthesis of a fluorinated carnitine derivative, fluoromethylcarnitine (FMC), and its radiolabelled equivalent, [18F]fluoromethylcarnitine ([18F]FMC), are described, and their ability to quantitatively measure carnitine transport and downstream metabolism in a variety of settings are shown, from simple cell models to living subjects. Finally, [18F]FMC PET is used to visualise elevated carnitine utilisation in a xenograft model of non-small cell lung cancer.

Breast cancer imaging without gadolinium-based contrast agent: A review of current applications and future trends.

Atherosclerosis is a major global health challenge, with limited diagnostic and therapeutic options. Macrophages drive disease progression, but their tissue-specific phenotypes and functions remain poorly defined. This study aims to elucidate macrophage-driven mechanisms by characterizing their functional diversity across key metabolic and vascular tissues. We used single-cell RNA sequencing (scRNA-seq) and Translating Ribosome Affinity Purification sequencing (TRAP-seq) to profile macrophage-specific gene programs in a mouse model of atherosclerosis across the aorta, adipose tissue, and liver. Our data highlights tissue-specific macrophage gene programs and identifies markers that are shared across mouse and human plaques. First, we identified soluble Trem2 as a potential circulating biomarker for differentiating between asymptomatic and symptomatic individuals. Secondly, we leveraged the pronounced expression of Folr2 and Slc7a7 to explore the potential of folate and glutamine as PET tracers for disease burden assessment through in vivo positron emission tomography (PET) imaging. Finally, we show that knockout of Slc7a7 inhibits acetylated low-density lipoprotein (AcLDL) uptake and dampens the gene signature linked to lipid-associated macrophages. This suggests that glutamine signaling may play a critical role in foam cell formation, a key event in atherosclerosis. Our findings provide novel insights into macrophage-specific gene programs during atherosclerosis progression and identify a set of promising biomarkers that can serve as a resource for future studies. These findings could significantly contribute to improving the diagnosis, monitoring, and treatment of atherosclerosis.

That the incorporation of N-methyl amino acids adjacent to a hydrolytic, azamacrocyclic metal complex results in rate-tunable, metal-mediated amide bond cleavage (TMAC) under physiological conditions. Spectroscopic and crystallographic data provide unprecedented mechanistic insight: the Ga3+ complex of (7-amido-1,4,7-triazonane-1,4-diyl)diacetic acid polarizes the amide bond proximal to canonical and noncanonical amino acids, forming two coordination isomers with different cleavage rates, N3O3 (fast) and N4O2 (slow) in aqueous solution. Both were characterized by NMR spectroscopy and identified by single-crystal X-ray diffraction. Subsequent hydrolysis of the amide bond occurs by exogenous nucleophilic attack, as demonstrated by 18O-isotope labeling experiments and proceeds with a variable rate, depending on the nature of the amino acid side chain and amide-methylation status. The in vivo applicability of TMAC was subsequently demonstrated by pharmacokinetic modulation of a cancer targeted, 68Ga-labeled radiopharmaceutical. Specifically, 6 serum-albumin binding chelates, linked to a peptide targeting the prostate specific membrane antigen (PSMA) were constructed. Variable amino-acid-chelate linkers allow tuning of the rate of release and clearance of the radioactive isotope. Indeed, diagnostic positron emission tomography (PET) imaging, metabolite and biodistribution analysis indicate that rate tunable cleavage and release of the 68Ga-chelate minimize tracer accumulation in blood and liver compartments while maximizing tumor uptake. In contrast, a [68Ga]Ga-chelate incorporating a noncleavable glycine linker, exhibited elevated blood and liver uptake with moderate tumor localization. Taken together, TMAC provides remarkable control over the in vivo behavior of targeted pharmaceuticals.

Approximately 30% of patients with schizophrenia do not respond to antipsychotics. While schizophrenia has been primarily explained by the dopamine dysfunction hypothesis, treatment-resistant schizophrenia (TRS) may involve a different pathophysiology. Neuromelanin (NM), a product of dopamine metabolism in the substantia nigra (SN), indirectly measures long-term dopamine synthesis capacity. Few studies have examined SN NM levels in TRS. Therefore, we investigated the relationship between SN NM levels and treatment responsiveness in schizophrenia. We included age- and sex-matched TRS, patients with schizophrenia in remission of positive symptoms (SZ-R), and healthy controls (HCs). Neuromelanin-sensitive magnetic resonance imaging was used to measure SN NM signals. We also evaluated clinical symptoms and cognitive impairment. We conducted voxel-wise analyses of NM contrast-to-noise ratio (CNR) to compare groups pairwise. Correlation analyses examined relationships between NM signals and symptom severity. Seventy-two participants (n = 24 per group) completed the study. The TRS group had higher dorsal SN CNR than the HC group (510 out of 1948 voxels at p < 0.05, corrected p = 0.005, permutation test). In contrast, no significant differences were observed in the other comparisons. No significant correlations were found between NM CNR and clinical severity. Our findings contrast with previous positron emission tomography studies on dorsal striatal dopamine function. Since the dorsal SN contributes to both the mesolimbic and nigrostriatal pathways, with a relatively greater role in the former, dopamine functions in these pathways may play different roles for treatment responsiveness. Further research with multimodal imaging is needed to examine dopamine function and antipsychotic treatment responsiveness in schizophrenia.

In proton therapy, a conformal and precise radiation dose is delivered to tumors, resulting in improved treatment outcomes and higher survival rates. However, the depth-dose profile (Bragg Peak) poses a significant concern for clinical applications, as even minor spatial uncertainties can lead to undesired doses in normal tissues. Imaging techniques like Positron Emission Tomography (PET) have been proposed to address this challenge. This study evaluates the suitability of the easyPET.3D system for assessing 3D proton beam profiles through Monte Carlo simulations. The primary focus is on accurately predicting the distribution ofβ+emitters produced in a phantom after proton beam irradiation. Simulations were performed to model the irradiation of homogeneous and heterogeneous phantoms with monoenergetic protons (energies ranging from 80 to 160 MeV) and obtain the corresponding PET images of the phantom's irradiation. Theβ+production map (ground truth) generated in the phantoms showed reproducible agreement with the PET image obtained. For the energy beams simulated in this study, the relative deviation between the ground truth image and the PET 3D image was less than 14%, for every beam energy. The easyPET.3D system could also differentiate between the two materials in the heterogeneous phantom. Additionally, the distance between the Bragg peak and the maximum intensity of PET image profile obtained remained constant across all simulated proton energy beams, around 11.7 mm. This suggests that the easyPET.3D system can be used as an effective tool to assess beam quality in proton therapy by measuring theβ+activation map generated in phantoms and correlate it with the beam's profile.

Trace amine-associated receptor 1 (TAAR1) is an emerging therapeutic target with various implications in neuropsychiatric and metabolic disorders. However, the absence of a suitable positron emission tomography (PET) radioligand has precluded non-invasive quantification of TAAR1 expression and drug-receptor interactions in vivo. In this study, we report the preclinical development of [18F]TAAR1-2203, a fluorine-18 labeled PET ligand suitable to image TAAR1 expression in peripheral tissues. [18F]TAAR1-2203 ([18F]RO5263397) was obtained via copper-mediated radiofluorination. In vitro stability was assessed in formulation, serum and using liver microsomes. Specific binding was evaluated by in vitro autoradiography, ex vivo biodistribution, and PET imaging under baseline and blockade conditions with structurally distinct TAAR1 agonists, as well as in TAAR1 knockout (KO) mice. Receptor occupancy studies were conducted in the pancreas - a peripheral organ with high physiological TAAR1 expression. TAAR1-2203 exhibited high TAAR1 affinity in competition binding assays across species, with Ki values of 0.9 nM (mouse) and 5.7 nM (human). Tracer stability was corroborated by cross-species microsomal incubations and ex vivo radiometabolite analyses in mice. In peripheral tissues with known TAAR1 expression, [18F]TAAR1-2203 displayed robust signal intensity that was significantly reduced under pharmacological blockade or in TAAR1 KO mice, thus confirming specific receptor binding. Although [18F]TAAR1-2203 appeared to cross the blood-brain barrier based on brain time-activity curves and ex vivo radiometabolite analysis, no specific binding was observed in the CNS. Target occupancy studies in the pancreas demonstrated dose-dependent blockade, with a calculated D50 of 0.67 µmol/kg for a structurally distinct potent TAAR1 agonist. [18F]TAAR1-2203 represents the first PET radioligand for TAAR1 imaging with favorable in vitro and in vivo performance characteristics, enabling non-invasive assessment of receptor expression and drug occupancy in peripheral TAAR1-expressing tissues. [18F]TAAR1-2203 holds promise for translational application in various drug development programs.

This case presents a rare instance of ulcerative colitis (UC) relapse in the functionally isolated left colon following surgery for rectal cancer associated with UC. A 62-year-old man, suspected of having cancer based on positron emission tomography (PET)-computed tomography (CT) findings and elevated carcinoembryonic antigen levels, underwent robot-assisted low anterior resection and temporary transverse colostomy. Postoperatively, leakage and infection made it difficult to administer conventional local treatments or corticosteroids; however, remission was achieved with the oral α4-integrin inhibitor, carotegrast methyl, allowing for stoma closure. To our knowledge, this report is the first to describe the use of carotegrast methyl for recurrent UC in a diverted colon. This case demonstrates that carotegrast methyl may serve as an effective steroid-sparing option for UC relapse in complex postoperative anatomical contexts. It also highlights the potential utility of PET-CT as an adjunctive diagnostic tool for UC-associated cancer.

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder with two main subtypes: MSA with predominant cerebellar ataxia (MSA-C) and MSA with predominant parkinsonism (MSA-P). The latest diagnostic criteria emphasize the importance of neuroimaging markers from magnetic resonance imaging (MRI) alongside clinical symptomatology assessment.This study investigates the relationship between visual MRI markers and MSA subtypes, clinical features, and cerebral glucose metabolism and striatal dopaminergic degeneration. 89 MSA patients (67 MSA-P, 22 MSA-C) underwent extensive clinical and neuropsychiatric evaluations, routine MRI scans to assess markers like the "hot cross bun" (HCB) sign, putaminal iron deposition, midbrain to pons (M/P) ratio, and cerebellar atrophy. Positron emission tomography (PET) imaging with 18F-fluorodeoxyglucose (18F-FDG) and 11C-2β-carbomethoxy-3β(4-fluorophenyl) tropane (11C-CFT) were conducted to evaluate brain metabolism and striatal dopaminergic uptake abnormalities. Canonical Correlation Analysis revealed significant associations between clinical symptoms and MRI markers, particularly HCB sign, M/P ratio, and putaminal iron deposition. The HCB sign and M/P ratio correlated with cerebellar dysfunction, while putaminal iron deposition correlated with parkinsonism severity, particularly in MSA-P. Cerebellar and putaminal metabolism negatively correlated with their respective structural changes. However, putaminal iron deposition showed no significant correlation with striatal dopaminergic uptake. Visual MRI markers are crucial for diagnosing MSA and delineating disease subtype and symptom severity. Supratentorial and infratentorial MRI markers reflect the severity of parkinsonism and cerebellar dysfunction, respectively. Putaminal iron deposition reflects the severity of parkinsonism, suggesting that iron deposition plays an important role in the pathophysiological mechanisms contributing to parkinsonism in MSA. CCA = Canonical correlation analysis; 11C-CFT = 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane; 18F-FDG = 18Ffluorodeoxyglucose; GCIs = glial cytoplasmic inclusions; HAMA = Hamilton anxiety scale; HAMD = Hamilton depression scale; HCB = hot cross bun; H-Y = Hoehn and Yahr; MCP = middle cerebellar peduncles; MMSE = mini-mental state examination; MoCA = Montreal cognitive assessment; M/P = midbrain to pons; MSA = multiple system atrophy.

Giant cell myocarditis is a rare cardiac disorder that can lead to rapid deterioration and poor outcomes. It presents with a wide array of symptoms, including heart failure, ventricular arrhythmias, or atrioventricular block. Its features overlap with other inflammatory cardiac conditions, particularly cardiac sarcoidosis, which can lead to diagnostic challenges. Diagnostic modalities, including cardiac magnetic resonance and positron emission tomography, can detect myocardial inflammation but are not diagnostic. Endomyocardial biopsy remains a gold standard, showing a diffuse inflammatory infiltrate with multinucleated giant cells and extensive myocyte necrosis. Management involves prompt initiation of immunosuppressive treatment, as well as management of the cardiac complications when indicated. Despite treatment, mechanical circulatory support or cardiac transplantation is required in numerous patients, and recurrence in the allograft has been noted. In this review, we discuss the clinical presentation, diagnostic strategy, differential diagnosis with sarcoidosis, and modern treatment options for giant cell myocarditis, emphasizing early diagnosis and newer therapies.

Lymph node metastasis (LNM) is strongly associated with a poor survival in patients with intrahepatic cholangiocarcinoma (ICC). However, the indications for lymph node dissection (LND) are controversial. This study assessed the accuracy of preoperative imaging for detecting LNM. Eighty-nine patients who underwent curative resection for ICC between 2001 and 2022 were enrolled and analyzed retrospectively. Lymph node status was evaluated preoperatively using contrast-enhanced computed tomography (CT) and positron emission tomography (PET)/CT. Patients were grouped according to their LND status (LND or no LND). Patients in the LND group were further grouped according to pathological LNM status (pN+, LNM-positive; and pN0, LNM-negative). Adequate LND was performed in 44 (49.4%) patients, among whom LNM was diagnosed in 17 (38.6%). The 3-year overall survival rates in patients with LND/pN+, LND/pN0, and no LND were 16.2%, 70.0%, and 70.7%, respectively. The corresponding 3-year recurrence-free survival rates were 11.8, 52.6, and 42.6%, respectively. A lymph node diameter > 8mm on preoperative CT was an independent predictor of LNM. The maximum standardized uptake value (SUVmax) on PET/CT was significantly associated with LNM. Lymph node diameter and SUVmax predicted LNM in patients with resectable ICC. A preoperative lymph node evaluation can ensure optimal treatment outcomes.

Experimental evidence suggests that activated microglia induce astrocyte reactivity in neurodegenerative disorders, such as Alzheimer's disease (AD). In this study, we investigated the association between microglial activation and amyloid-β (Aβ) with reactive astrogliosis in individuals across the AD spectrum. We examined 101 individuals using positron emission tomography radiotracers to assess Aβ deposition ([18F]AZD4694), tau aggregation ([18F]MK-6240) and microglial activation ([11C]PBR28), along with plasma biomarkers for astrocyte reactivity (GFAP) and tau phosphorylation (p-tau217). We further evaluated 251 individuals with cerebrospinal fluid levels of the microglial marker sTREM2. We found that Aβ pathology was associated with astrocyte reactivity across cortical brain regions only in the presence of microglial activation. The microglia-dependent effects of Aβ on astrocyte reactivity were further related to cognitive impairment through tau phosphorylation and aggregation. Our results suggest that microglial activation plays a key role in Aβ-related astrocyte reactivity, which, in turn, contributes to downstream pathological features of AD.

Objective This study aimed to assess the value of preoperative [ 68 Ga]Ga-FAPI-04 positron emission tomography (PET) for evaluating pathological complete response (pCR) in patients with gastrointestinal adenocarcinomas receiving neoadjuvant therapy (NAT). Materials and Methods A retrospective analysis was conducted on patients with gastrointestinal adenocarcinomas who received [ 68 Ga]Ga-FAPI-04 PET/MR scans between February 2021 and January 2024. The enrolled patients had completed preoperative NAT, undergone contemporary enhanced CT or MR scans, and received surgery within one month after PET imaging. Clinical data, imaging evaluations, PET parameters (standardized uptake values [SUVs], SUVs standardized by lean body mass [SUL], FAPI-positive tumor volume [FAPI-PTV], and total lesion burden [FAPI-TL]), and surgical pathology results were collected. Each parameter’s sensitivity, specificity, and diagnostic cutoff for predicting pCR were determined via receiver operating characteristic curve analysis. Logistic regression analysis identified independent predictors of pCR. Results Sixty-five patients were enrolled, and 22 patients achieved pCR according to surgical pathology. In visual evaluation, [ 68 Ga]Ga-FAPI-04 PET was limited in its ability to assess pCR, with 16 false positives and 1 false negative. The dichotomization using the FAPI-PTV cutoff value (&amp;lt;1.92 cm 3 ) improved the specificity for predicting pCR to 72.7%, while retaining a high sensitivity of 93.0%. Enhanced CT or MR scans had the sensitivity and specificity of 72.7% and 93.0% in predicting pCR, respectively. According to the logistic regression analysis, a FAPI-PTV&amp;lt;1.92 cm 3 was an independent predictor for patients who achieved a pCR ( p &amp;lt;0.05). Conclusion [ 68 Ga]Ga-FAPI-04 PET shows promise in predicting pCR among patients with gastrointestinal adenocarcinomas following NAT. FAPI-PTV derived from [ 68 Ga]Ga-FAPI-04 PET may provide an effective clinical tool for guiding further treatment.

The oxytocin/oxytocin receptor (OT/OTR) signalling system is involved in socioemotional behaviours, garnering interest as a therapeutic target across multiple clinical conditions. Despite its potential, our limited understanding of how to optimally target it and the scarcity of molecular tools for in vivo studies hinder therapeutic development. Molecular imaging techniques, such as Positron Emission Tomography (PET), can bridge this gap by furnishing direct insights into ligand biodistribution, receptor visualisation and ligand-receptor engagement. Here, we report the design, synthesis and biochemical and pharmacological characterisation of five OT-like peptides as novel PET tracers for investigating the OT/OTR signalling system. dOTK8[SFB] emerged as the most promising OT-like lead. The radioactive version [18F]dOTK8[SFB] was produced using a microfluidic reaction approach and validated by preclinical PET imaging of healthy rats after intravenous ligand administration. [18F]dOTK8[SFB] exhibited specific accumulation in OTR-rich tissues, affirming OTR-specificity and suitability as a new OT-like PET radiotracer for investigating OT/OTR biodistribution in humans.

Partial volume effects (PVE) remain a major challenge in quantitative single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging, often compromising both accuracy and reproducibility. While numerous Partial Volume Correction (PVC) methods have been proposed, their clinical translation is still limited. This review provides a clinically oriented evaluation of PVC methods with a particular focus on state-of-the-art applications in neurology, cardiovascular imaging, oncology, and radiopharmaceutical therapy dosimetry, highlighting where these techniques offer the greatest added value. In addition, we outline which PVC techniques have the potential to be used in clinical practice and which remain primarily suited for research purposes, along with their suitability in each of the above-mentioned clinical domains. Finally, this review addresses the central question of whether PVC is essential in clinical practice or whether its impact is context dependent. This review categorizes PVC approaches into three partially overlapping classes: reconstruction-based, post-reconstruction-based, and AI-driven or hybrid methods. Each class is further divided into anatomical and non-anatomical subcategories. We systematically compare their clinical applicability across key dimensions: quantitative accuracy, lesion detectability, robustness to noise and artifacts, anatomical dependence, generalizability across scanners and tracers, and clinical readiness. PVC techniques often improve quantitative accuracy in small structures and in regions affected by spill-over from adjacent high-uptake tissues. However, these benefits can come at the cost of increased noise or edge artifacts, which may limit their robustness for routine clinical use. Post-reconstruction methods are sensitive to segmentation errors, while AI-driven models, despite their promise, require further validation using clinical benchmarks, comparison to ground truth, and testing on diverse datasets. Issues, such as generalizability and interpretability remain significant barriers. This review emphasizes the importance of application-tailored PVC protocols for reliable quantitative imaging in neurology, cardiology, oncology, and radiopharmaceutical therapy dosimetry. Not all PVC methods are beneficial; some may even impair interpretation in certain contexts. We provide a practical overview of which PVC approaches are most beneficial for each clinical scenario, aiming to guide both researchers and clinicians in selecting appropriate techniques for future studies and routine practice, and also outline key areas requiring further development for broader integration into research and clinical workflows.

Background/Objectives: Oral squamous cell carcinoma (OSCC) carries a risk of late metastasis not only in advanced stages but also in early stages. In this study, we built and tested radiomics-based machine learning (ML) models for predicting the risk of metastasis from early OSCC on 18F-FDG positron emission tomography (PET). Methods: Patients diagnosed with T1 or T2 squamous cell carcinoma who underwent a preoperative 18F-FDG PET-CT examination at a single institution between 2016 and December 2022 were included in this retrospective study. The presence or absence of late cervical lymph node metastasis was confirmed for all patients. Among the radiomics features extracted from the images, we selected those that were useful for predicting late metastasis and used them to create ML models. We then verified the prediction accuracy of the models. Results: A total of 109 subjects were included, of which 31 had late lymph node metastasis and 78 were without metastasis. The most accurate ML model created using radiomics features selected from the subject cases had an area under the curve of 0.977 and accuracy of 87.5%. Conclusions: We confirmed that ML models using radiomics features extracted from PET images can be useful for predicting late metastasis in patients with early-stage OSCC.

Several pieces of evidence have demonstrated the sigma-1 receptor (S1R) as a druggable protein with important therapeutic potentials, including neurodegeneration, cancer, and neuropathic pain. The density of S1R is altered in pathological processes so that its imaging is under study for diagnostic purposes. Thus, research has been focused on the development of S1R positron emission tomography (PET) radioligands, not only as diagnostic tools but also as powerful means to assist in the drug-development process. Herein, we comprehensively review the most important S1R PET radiotracers belonging to different classes that have been developed in the last two decades. Starting from the structural modifications impacting on the S1R affinity and selectivity, we report (i) the differences in metabolism and pharmacokinetics, (ii) the in vivo behavior in different animal models, (iii) the in vitro autoradiography outcomes, and (iv) the dosimetric profiles. The successful use of the best-performing S1R PET radiotracers in the characterization of novel S1R drugs is also reported together with the approaches to assess the potential for clinical translation. What emerges from this review is that, although the development of reliable PET agents appears to be extremely challenging, these radiotracers hold incredible potential and play a fundamental role in the exploitation of S1R in health and disease.

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT), and whole-body magnetic resonance imaging (WB-MRI) are superior to conventional CT and bone scan imaging for detecting metastatic disease in patients with prostate cancer. While these higher-accuracy imaging methods have already shown the potential to enhance patient outcomes, a thorough understanding of the relationship between the treatment landscape and disease volume on conventional imaging, as well as the prognostic significance of the prostate-specific antigen response, is crucial for determining how they can be more effectively incorporated. Prospective clinical trials are required to evaluate whether PSMA-PET/CT and WB-MRI can genuinely improve clinically relevant endpoints for patients through precise treatment adaptations. In this paper, we explore the specific opportunities of PSMA-PET/CT and WB-MRI as biomarkers in multiple clinical domains, including metastasis detection and staging, disease characterisation and aggressiveness assessments, biopsy target selection, impacts on treatment planning, evaluation of therapeutic response, and theranostics. We highlight the central research questions that require attention. KEY POINTS: Question Can PSMA-PET/CT and WB-MRI, with their superior ability to detect metastases in prostate cancer, truly improve patient outcomes? Findings High-accuracy imaging improves metastasis detection, staging, assessment of disease aggressiveness, and enables more personalised treatment planning for advanced prostate cancer patients. Clinical relevance PSMA-PET/CT and WB-MRI have the potential to alter the management of men with advanced prostate cancer, but prospective clinical trials are needed to confirm benefits for survival or quality of life before recommending routine use.