the Quarterly Journal of Nuclear Medicine and Molecular Imaging最新文献

Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostically challenging conditions due to their diverse etiologies and non-specific presentations. Despite advances in diagnostic techniques, a significant proportion of cases remain unexplained, often leading to delays in treatment and increased healthcare burden. In recent years, [¹⁸F]FDG-PET/CT has emerged as a powerful diagnostic tool offering whole-body metabolic imaging, particularly valuable in the early stages of disease when structural changes may be absent. In this review a literature search was conducted in PubMed and Web of Science for original studies on the use of FDG-PET/CT in adults with FUO/IUO published between January 2005 and June 2025. The authors evaluated the diagnostic yield and clinical impact of [¹⁸F]FDG-PET/CT in adults with FUO/IUO based on 56 studies comprising over 7,400 patients. The [¹⁸F]FDG-PET/CT was helpful in up to 90% of cases when both true-positive and true-negative results were considered. Furthermore, [¹⁸F]FDG-PET/CT led to changes in patient management in a substantial proportion of cases, particularly when used early in the diagnostic algorithm. It demonstrates robust diagnostic performance, guiding therapeutic decisions, and guide subsequent interventions hereby avoiding futile examinations. Despite its growing recognition, standardization in study design and outcome reporting is needed to further consolidate its role in clinical guidelines.

Background: One can assess cortical defects on the early images of [99mTc]Tc-MAG3 renography. We aimed to assess interobserver and intraobserver reproducibility for detecting renal cortical defects using [99mTc]Tc-MAG3 for adults and children; identify causes for poor inter- and intraobserver reproducibility and to assess the effect of the kidney to background ratio (KTBR) on reproducibility.

Methods: One hundred adult and 200 pediatric renograms were included. The observers reviewed the summed 1-minute posterior images for the first four minutes to detect cortical defects. Interobserver reproducibility between three observers and intra-observer reproducibility for two observers were determined. Agreement was tested using percentage agreement, Krippendorff's reliability coefficient alpha and Cohen's kappa statistic. The association between KTBR and agreement was evaluated.

Results: Interobserver agreement on the 1-2 minutes images was 78 (95% CI: 74.8-82.7%) and 79.7 (95% CI: 75.9-83.5%) for left and right kidneys respectively. Intraobserver percentage was 89.7% (95% CI: 86.2-93.1%) for the senior and 80.7% (95% CI: 76.2-85.2%) for the junior observer. In 13.5% (27) of the adult and 4.5% (19) of the pediatric kidneys the difference in image interpretation between the observers would have had a clinical impact. If the KTBR is ≤2, the percentage agreement was between 61.5% and 64.8%. In cases with a KTBR >2, the percentage agreement was between 83.6% and 87.1%.

Conclusions: The percentage interobserver agreement was moderate. Disagreement between normal and abnormal cases were infrequent. The interobserver reproducibility was decreased when the KTBR was ≤2.

Introduction: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are among the most challenging diagnoses in clinical routine. [¹⁸F]FDG positron emission tomography/computed tomography (PET/CT) is a valuable diagnostic tool, particularly when conventional imaging and laboratory investigations fail to identify the root cause. While its diagnostic accuracy in FUO/IUO settings is high, several issues still remain to be addressed. Long axial field of view PET/CT and the availability of novel radiopharmaceuticals for molecular imaging may significantly advance the field of nuclear medicine and molecular imaging in FUO/IUO.

Evidence acquisition: This scoping review conforms to the "Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews Checklist". An extensive literature search of PubMed/MEDLINE database was performed to find relevant published articles on the use of LAFOV PET/CT and novel radiotracers in FUO/IUO settings.

Evidence synthesis: LAFOV PET/CT provides faster whole-body imaging, improved sensitivity, and the ability to perform ultra-low-dose scans. These benefits are particularly valuable for special populations, such as pediatric patients, ICU patients, and pregnant women, where motion artifacts, radiation exposure, and procedural complexity are major concerns. Additionally, novel radiotracers, including FAPI and CXCR4-targeted agents, offer promising specificity for inflammatory or infectious etiologies beyond FDG, potentially improving diagnostic accuracy and reducing false positives.

Conclusions: LAFOV PET/CT and emerging radiopharmaceuticals represent major advancements in the diagnostic workup of FUO/IUO. They enhance lesion detection, reduce scan burden, and may improve outcomes, particularly in vulnerable populations. Further clinical studies are needed to standardize protocols and validate these tools in broader clinical practice.

Prostate-specific membrane antigen-targeted radioligand therapy (PSMA RLT) has recently emerged as a promising treatment for patients with metastatic prostate cancer. Building on the success of PSMA PET diagnostics, PSMA RLT has attracted interest from both research institutions and pharmaceutical companies, leading to a progressive increase in clinical trials over the past decade. In 2022, the first PSMA RLT agent, [¹⁷⁷Lu]Lu-PSMA-617, was approved by the FDA and EMA for the treatment of mCRPC patients progressing after standard therapies. Since then, the number of centers offering PSMA RLT has grown rapidly worldwide. In March 2025, the FDA expanded the indication for [¹⁷⁷Lu]Lu-PSMA-617 to include taxane chemotherapy-naïve mCRPC patients. Current research studies are focusing on expanding the indications for PSMA RLT, developing new PSMA-targeting agents, exploring alternative radionuclides such as alpha and Auger electron emitters, and investigating combination strategies. Despite these advancements, several significant challenges remain in clinical implementation, global access, and availability. To present, there is high variability among different countries and institutions in patient selection and treatment protocols. Moreover, the distribution of centers offering the treatment is highly heterogeneous, with significant disparities across different countries. Furthermore, workforce shortages are already hindering its widespread diffusion and are expected to limit its expansion, particularly in low and middle-income countries. Many barriers need to be overcome in the coming years to standardize treatment protocols, guarantee fair global access to the treatment, and achieve widespread accessibility. Addressing these challenges is crucial to maximize the potential of PSMA RLT as a leading treatment for prostate cancer.

With the growth and surge of prostate cancer theranostics globally, multiple targeted radionuclide therapy (TRT) agents have been utilized to aim to provide a tumoricidal effect to patients who would benefit from TRT. Despite the fact that approved isotopes such as Strontium-89, Samarium-153 and Radium-223 exist, Lutetium-177 prostate specific membrane antigen (PSMA) has revolutionized the impact of radioligand therapy (RLT) in this domain. Key defining clinical trials such as the VISION, TheraP and PSMAfore trials have given clear evidence of the benefit of PSMA RLT in the treatment landscape of metastatic castrate resistant prostate cancer. A number of other radioisotopes in the PSMA RLT domain have also more recently come into the field, notably Terbium-161, Copper- 67 and Iodine-131. Targeted Alpha Therapy (TAT) has grown significantly as well over the last few years owing to physical properties of its high linear energy transfer and DNA damage provided by alpha particles in comparison to beta particles. Actinium-225 PSMA based TAT has formed the basis of prostate cancer theranostics since its initial application, however, many other alpha isotopes are being explored owing to some of the side effects that Actinium-225 presents. Astatine-211, owing to its shorter half-life, has become a more attractive option for its potential utilization in prostate cancer theranostics. Whilst there is preclinical work detailing its efficacy in suppressing tumor growth and limited toxicity profiles, translation into humans is still in its infancy and requires further exploration. A number of clinical trials have utilized Astatine-211 in other malignancies with virtually no work related to prostate cancer. Moreover, the logistics and infrastructure required to support global efforts to make Astatine-211 more readily available should be high on the agenda as well. This narrative review of the literature aims to showcase the current status of Astatine-211 efforts in prostate cancer care with available data (including clinical trials).

Metastatic castration-resistant prostate cancer (mCRPC) is an unavoidable advanced condition associated with short-term survival and poor prognosis. It is a heterogeneous disease, difficult to monitor based only on serum PSA levels. For this reason, systematic use of PSMA PET-based response criteria should be considered to assess therapy efficacy in mCRPC to improve treatment decision-making, patients' outcomes, and cost-effectiveness. Our review focuses on most common morphologic and metabolic response criteria and their application for the detection and therapy response assessment of PC patients, particularly in the setting of mCRPC, highlighting relative strengths and weaknesses, as well as potential future applications in the era of RLT.

Introduction: Neuroendocrine prostate cancer (NEPC) is a rare cancer subtype with significant prognostic implications. This systematic review aims to explore the current landscape of positron emission tomography (PET) imaging and radionuclide therapy in this rare entity.

Evidence acquisition: The Scopus and PubMed online databases were systemically reviewed to identify relevant studies on the topic of interest.

Evidence synthesis: A total of 60 studies reporting such evidence in 102 patients were retrieved. A total of 179 PET/CT examinations were performed across all NEPC patients, with [¹⁸F]Fluorodeoxyglucose ([¹⁸F]FDG) being the most frequently utilized radiotracer (45% of NEPC patients), followed by [⁶⁸Ga]Ga-DOTA-peptides (22%), [⁶⁸Ga]Ga-prostate specific membrane antigen ([⁶⁸Ga]Ga-PSMA) (18%), and other PET tracers (15%). Single-modality PET/CT imaging was mostly employed to evaluate NEPC extent, detect unusual metastatic sites, assess therapy response, and guide for biopsy sites in cases of hormone-secreting NEPC. Multimodal PET/CT utilizing dual- or triple-tracer approaches was employed for collective NEPC interpretation, assessment of heterogeneity, therapy response assessment, and determination of radionuclide therapy eligibly. For treatment, 16 [¹⁷⁷Lu]Lu-DOTATATE cycles, administered to 7 patients, produced effective disease control in all patients. One patient received both [¹⁷⁷Lu]Lu-PSMA and [¹⁷⁷Lu]Lu-DOTATATE, achieving partial response, while another patient receiving 4 [¹⁷⁷Lu]Lu-PSMA cycles also showed a partial response.

Conclusions: The multimodal molecular imaging approach appears to be the most effective for NEPC evaluation and determination of radionuclide therapy eligibility. [¹⁷⁷Lu]Lu-based therapies seem to be a compelling treatment approach to be pursued in eligible cases, although larger studies are needed to confirm the current findings.

Background: This study aims to further strengthen the evidence of tumor sink effect (TSE) and to confirm this phenomenon in patients undergoing ²²⁵Ac/¹⁷⁷Lu-PSMA tandem radioligand therapy.

Methods: The study included a total of N.=31 mCRPC patients who undergone two cycles of [¹⁷⁷Lu]Lu-PSMA-617 RLT, with at least one cycle being augmented by [²²⁵Ac]Ac-PSMA-617. For pre- and post-therapeutic [⁶⁸Ga]Ga-PSMA-11 PET/CT scans the standardized uptake value (SUVmean) of the liver, kidneys, parotid glands, and spleen as well as the total lesion PSMA (TLP) were assessed and compared.

Results: The mean TLP value decreased by 31.32% after two cycles of PSMA-RLT. Overall, significant increases in SUVmean were noted in the spleen (P=0.002) and liver (P=0.009). Especially, responders exhibited significant SUVmean increases in the spleen (P<0.001, baseline mean: 5.35 vs. follow-up mean: 7.28), liver (P=0.001, 4.21 vs. 5.00), and kidney (P=0.003, 17.30 vs. 20.43). Correlation analysis revealed significant relationships between change in TLP and change in SUVmean in the parotid gland (r=0.408, P=0.023) and spleen (r=0.410, P=0.022). The strength of TSE varied with tumor size, with an increase in tumor burden leading to a stronger TSE.

Conclusions: This analysis demonstrates the presence of the TSE in mCRPC patients undergoing the innovative ²²⁵Ac/¹⁷⁷Lu-PSMA tandem radioligand therapy concept. TSE may hold significant clinical implications and may play a role towards more individualized RLT.