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

[¹⁸F]FDG PET/CT plays a pivotal role in the contemporary management of malignant lymphoma, and is crucial for accurate staging, response assessment, and treatment planning in pediatric Hodgkin lymphoma (pHL). Treatment response evaluation in pHL and in particular interim [¹⁸F]FDG PET/CT done after few cycles of chemotherapy is critical for early prediction of outcome. It helps in identifying patients who would respond well and might safely omit radiotherapy, thereby reducing the risk of late adverse effects. Consequently, consensus international guidelines emphasize the standardized use of [¹⁸F]FDG PET/CT in pHL, thus facilitating comparison of clinical trial outcomes and optimizing individualized patient care worldwide. In the present review we aim to summarize essential aspects of [¹⁸F]FDG PET/CT in pHL, by providing new approaches and future developments.

In this review we summarize the current knowledge on fever of unknown origin (FUO). Fever of unknown origin remains a diagnostic challenge even despite increasing diagnostic possibilities since its first definition. Uniform definition of FUO is pivotal to correctly select patients that benefit from the extensive workup that may be needed. The number of conditions associated with FUO is still increasing. Epidemiologic differences and differences in diagnostic possibilities are a challenge when comparing outcomes from cohorts with different epidemiologic backgrounds. The diagnostic protocol that was proposed as early as 2007, with a central role for ¹⁸F-FDG-PET/CT, still remains the golden standard for the workup of FUO. Early use of new diagnostic modalities, including the use of metagenomic next generation sequencing and artificial intelligence, may shorten the diagnostic delay. In patients remaining undiagnosed, second opinion in an expert center can be considered, especially when therapeutic trials are considered. An increasing subset of patients presents with absent inflammatory parameters. Correct evaluation within a febrile episode is important in patients with intermittent disease, but these patients may also suffer from habitual or functional hyperthermia. We advise to let go of these terms and introduce the criteria for temperature elevation with missing inflammatory parameters (TEMP) syndrome.

¹⁸F fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has established itself as a fundamental non invasive diagnostic technique in the investigation of patients with fever (FUO) and inflammation of unknown origin (IUO). These conditions are for definition challenging due to potential wide underlying causes, including inflammatory disease, infectious disease, malignancies and miscellanea. Sometimes no diagnosis is reached. Data about the diagnostic performances of [¹⁸F]FDG PET/CT in special populations, such as pediatrics, end-stage renal disease, HIV and intensive care unit (ICU) patients, are preliminary and heterogeneous. Our review aims to describe the role of [¹⁸F]FDG PET/CT imaging in these specific populations and focus on the potential clinical impact on diagnosis and patient management. Findings presented in the literature demonstrated a good diagnostic yield of FDG PET/CT in the study of these patients affected by FUO/IUO with performances similar to adult general populations. A positive PET scan is often contributory and, in some cases, even essential to diagnosis, whereas a negative scan may be equally important as it excludes focal disease and predicts a favourable prognosis. Further studies with larger populations would be desirable.

Background: The aim is to retrospectively evaluate toxicity and outcomes of re-irradiation (re-RT) for macroscopic local relapse in patients with prostate cancer (PCa) treated with previous definitive or postoperative radiotherapy (RT).

Methods: Thirty-six patients affected by local relapse after previous definitive or post-operative RT were treated with re-RT in our institute. Treatment dose was 25-30 Gy in 5 fractions. Gastrointestinal (GI) and genitourinary (GU) toxicity was reported according to Common Terminology Criteria for Adverse Events score version 5. Endpoints were Biochemical Relapse Free Survival (BRFS) and Distant Metastases Free Survival (DMFS), assessed with Kaplan-Meier analysis. Univariate and multivariate Cox regression was carried out to evaluate the association between clinical factors and survival outcomes.

Results: Twenty-six patients received re-RT after definitive RT and 10 after post-operative RT. At time of re-RT median PSA was 2.57 ng/mL (range 0.23-13.10) and local relapse was detected with choline-Prostate Specific Membrane Antigen (PSMA) - Positron Emission Tomography (PET) or magnetic resonance imagig (MRI) in 18, 17 and one, respectively. Median Clinical Target Volume (CTV) was 17.8 cc (range 1-93.1). In 39% of patients the target corresponds to macroscopic relapse, while in 61% target was the whole prostate or prostate bed. Median follow-up was 28.2 months. No late >2 side effects were collected. Only one patient experienced GI toxicity (G2), while GU side effects were observed in eight patients (six G1 and two G2). Median BRFS survival was 19.0 months, with 1- and 2-year BRFS rates of 63.5% (95% CI 42.5-78.6) and 37.0% (95% CI 17.5-56.8), respectively. At univariate analysis, PSA value at time of re-RT was a predictive factor for BRFS (HR 1.43, 95% CI 1.19-1.73; P=0.000). DMFS rates at 1 and 2 years were 88.0% (95% CI 66.8-96.0) and 72.4% (95% CI 48.1-86.8), respectively. Median DMFS was 19.6 months in with re-RT of the relapsing nodule, while was not reached in patients treated on the whole prostate gland or surgical bed. At univariate analysis, irradiation of the macroscopic relapse vs the whole gland/bed (HR 5.91, 95% CI 1.35-25.80; P=0.018) and increasing PSA at time of re-RT (HR 1.20, 95% CI 1.01-1.41; P=0.030) were negative predictive factors. At multivariate analysis, treatment of the macroscopic relapse only remained an independent predictive factor of distant metastases free survival (DMFS) (HR 4.48, 95% CI 1.09-18.37; P=0.037).

Conclusions: Re-RT in patients treated previously with definitive or postoperative RT was safe and showed promising results in terms of toxicity and biochemical outcomes.

¹⁸F FDG PET/CT plays an important role in the investigation of fever of unknown origin (FUO), particularly after failure of conventional investigations to identify the source. However, its diagnostic yield is highly influenced by a wide range of factors including patient preparation, physiological variant, and treatment related factors. This review aims to provide an overview of the most common causes experienced in clinical practice, and how to avoid common pitfalls that may affect scan interpretation. For instance, elevated blood glucose levels, prolonged steroid therapy and recent interventions may reduce scan sensitivity, while artefacts from injection sites and brown fat uptake may mimic sites of disease. Careful preparation - including dietary modification, activity restriction and appropriate access selection - combined with clinical correlation and review of non-attenuation corrected images enhances interpretation, and as always, multidisciplinary discussions remain key.

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.

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.

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.

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.