¹³¹I whole-body scintigraphy (WBS) remains a cornerstone in the follow-up of differentiated thyroid carcinoma (DTC). However, radioiodine uptake is not specific, and many benign conditions can result in focal or diffuse radioiodine activity that mimics metastatic disease. A narrative literature review spanning more than five decades was conducted to identify and categorise reported sites of misleading radioiodine uptake on WBS in patients with DTC. Case reports, case series, original studies, and reviews were analysed with particular emphasis on the underlying mechanisms of uptake. The majority of false-positive findings were attributable to non-tumorous conditions, followed by benign neoplasms and, less frequently, non-thyroidal malignancies. Ectopic thyroid tissue was documented at numerous sites beyond classical thyroglossal duct remnants. Although pathological NIS expression was demonstrated in several non-thyroidal tumors, its presence did not consistently correlate with functional iodide transport. No single imaging feature reliably differentiates non-tumorous radioiodine uptake from true metastatic disease. Accurate interpretation, therefore, requires integration of clinical history, biochemical findings, and complementary imaging, particularly single-photon emission computed tomography/computed tomography (SPECT/CT). A mechanism-based approach to unexpected radioiodine uptake offers a practical strategy to reduce false-positive interpretations and avoid unnecessary diagnostic procedures.

Objective [68Ga]/[18F] labeled Prostate Specific Membrane Antigen (PSMA) is the radiotracer of choice for imaging localized and metastatic prostate cancer with high sensitivity and specificity. On the other hand, 2-[18F]fluoro-D-glucose (FDG) Positron Emission Tomograpy/Computed Tomography (PET/CT) may help to evaluate the tumor heterogeneity in patients with metastatic castration-resistant prostate cancer (mCRPC) and determine treatment eligibility for Prostate Specific Membrane Antigen (PSMA) targeted radioligand therapy (PSMA-RLT) . The aim of the study is to evaluate the biochemical and clinical parameters which can predict the presence of FDG-PSMA discordant disease. Material and Methods A total of 70 advanced mCRPC patients who underwent [68Ga]Ga-PSMA-11 PET and FDG PET/CT between August 2016 and June 2021 were retrospectively analyzed. Inter-tumoral heterogeneity was both visually and semi-quantitatively evaluated. Baseline clinical, laboratory and PSMA PET/CT related semi-quantitative parameters were analyzed to predict FDG discordant disease with logistic regression analysis. Results 29/70 (41.4%) of the patients had FDG-PSMA discordant disease. Overall 427 mismatch lesions (FDG+PSMA-) were detected: the majority of these lesions were in the bones (n = 236, 55.2%), lymph nodes (n = 95, 22.2%), and visceral organs (n = 88, 20.6%). Most significant parameters to predict FDG-PSMA discordant disease were liver metastases (HR= 26.5, 95%CI 2.3-302.9, P = 0.008) and serum AST (HR= 1.15, 95%CI 1.04-1.26, P = 0.007). Conclusion The presence of liver metastases and elevated AST may be easily used in clinical practice to predict FDG-PSMA discordant disease.

Multiple endocrine neoplasia (MEN) syndromes are rare hereditary disorders characterized by the development of multiple endocrine and non-endocrine tumours with variable penetrance and age-dependent expression. Although uncommon, these syndromes are highly relevant from both biological and clinical perspectives, as they exemplify the direct link between germline genetic alterations and tumorigenesis. Early tumour detection is critical in MEN syndromes because many associated neoplasms—such as medullary thyroid carcinoma (MTC), pancreatic neuroendocrine tumours (NETs), pheochromocytomas, and parathyroid disease—may remain clinically silent for prolonged periods while retaining malignant potential. Delayed diagnosis is associated with advanced disease and worse outcomes, whereas early identification enables curative or organ-preserving interventions. This clinical challenge has driven the development of integrated diagnostic strategies combining genetic testing, biochemical markers, and imaging. Among these, genetic testing plays a pivotal role, providing definitive diagnosis, enabling family screening, and guiding risk-adapted surveillance. The aim of this review is to provide a comprehensive synthesis of genetically driven diagnostics in MEN syndromes, outlining the current state of the art and future directions in precision medicine.

This review examines Marine-Lenhart syndrome (MLS), an uncommon thyroid disorder that combines Graves’ disease with autonomously functioning thyroid nodules (AFTNs) and demonstrates why nuclear medicine imaging is essential for accurate diagnosis and treatment planning. We reviewed case reports and case series published over the past three decades and analyzed clinical presentation, diagnostic approaches, prevalence rates, disease mechanisms, and treatment outcomes of MLS. This relatively rare syndrome occurs in approximately 0.8–4.3

BACKGROUND:Radioiodine (Na[131I]I) therapy is the cornerstone of systemic treatment for differentiated thyroid cancer (DTC), exploiting sodium-iodide symporter (NIS) expression for durable control. Up to 30-40% of advanced cases develop radioiodine-refractory disease (RAI-R DTC), marked by impaired iodine uptake, aggressive behavior, and poor response to Na[131I]I. Locoregional treatments, multikinase inhibitors (MKIs), and selective targeted agents improve progression-free survival but are not curative and carry cumulative toxicity, motivating precision-based alternatives. The primary objective of this review is to clarify the evolving theranostic paradigm in RAI-R DTC; the secondary objectives are to appraise redifferentiation and iodine-based theranostics for restoring or exploiting iodine avidity and to evaluate non-iodine theranostic strategies for cases where iodine biology is absent, impaired, or unreliable. METHODS:This narrative review synthesizes contemporary evidence on theranostic strategies in RAI-R DTC, drawn from available studies, clinical trials, and current guidelines, with an emphasis on redifferentiation and non-iodine approaches; a systematic search protocol was not applied. RESULTS:Theranostics couples target-specific molecular imaging with matched radionuclide therapy and response-adapted sequencing. Its most transformative application is redifferentiation, in which pharmacologic modulation of oncogenic signaling can restore iodine avidity and enable renewed, dosimetry-guided Na[131I]I treatment. Beyond iodine, somatostatin receptor (SSTR) imaging and peptide receptor radionuclide therapy (PRRT) have re-emerged in very selected cases, whereas alpha emitters remain investigational. Refractoriness is increasingly viewed as a reversible continuum rather than a fixed state. CONCLUSIONS:Theranostics can individualize RAI-R DTC treatment, restoring or exploiting iodine biology where possible and shifting to non-iodine targets where it is unreliable. Patient selection, timing, and integration with systemic therapy are central, and prospective validation is needed.

To compare the diagnostic performance of 18 F-Fluorodeoxyglucose (FDG) and 68Ga-fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) in gastrointestinal malignancies, with particular emphasis on lesion detection, peritoneal disease assessment, and the potential added value of dual-time-point FAPI imaging. Thirty-eight patients with histologically confirmed gastrointestinal cancers who underwent both FDG and FAPI PET/CT within a 4-week interval were retrospectively analyzed. FAPI PET/CT images were acquired at 10 and 60 min after tracer injection. Patient-level analyses (staging/restaging accuracy, impact on management) and lesion-based analyses (detection rate, characterization, maximum standardized uptake value [SUVmax] dynamics, lesion size) were evaluated against follow-up data as the reference standard. FAPI PET/CT demonstrated superior agreement with the reference standard compared with FDG PET/CT for staging and restaging (κ = 0.91 vs. 0.32). On lesion-based analysis, FAPI showed markedly higher detection rate for malignant lesions (86

PSMA PET/CT is commonly used for selecting candidates for [& sup1;Lu-7(7)]-PSMA radioligand therapy (LuPSMA RLT). However, discrepancies may occur due to pharmacokinetic and biodistribution differences between [Ga-6(8)]-PSMA-11 and [& sup1;Lu-7(7)]-PSMA-617 ligands. Such discordance risks underestimating disease burden and excluding eligible patients. We present a case of metastatic castration-resistant prostate cancer (mCRPC) in whom a PSMA-negative adrenal lesion on PET exhibited significant LuPSMA uptake post-therapy and was subsequently confirmed as FDG-avid. Complementary stereotactic body radiotherapy (SBRT) achieved metabolic remission. This case highlights the clinical significance of integrating post-therapy LuPSMA imaging and FDG PET/CT with systemic treatment to ensure accurate disease characterization and personalized management of PSMA-/FDG+ lesions in advanced prostate cancer.

AIM:To investigate the relationship between serum human epididymis protein 4 (HE4) levels and metabolic parameters of positron emission tomography (PET) imaging in patients with lung cancer. METHODS:Sixty non-small cell lung cancer (NSCLC) patients were included in this prospective study. Demographic information, smoking status, comorbid pathologies, preoperative HE4 levels, PET imaging metabolic parameters, disease stage and histopathology were recorded. RESULTS:Significant positive correlations between serum HE4 levels and all the metabolic parameters were observed (p < 0.05). In univariate regression analyses, it was observed that high serum HE4 levels could indicate tumor be squamous cell carcinoma (SCC) (p = 0.029), advanced T stage (p = 0.041), and have high maximum standart uptake value (SUVmax) (p = 0.017). CONCLUSION:Serum HE4 levels can be used as a biomarker to predict tumor burden and metabolic activity for NSCLC patients. Although sufficient per power analysis, this study may have benefited from further expansion, and by patient heterogeneity in TNM stage and tumor histology, potentially affecting the assessment of parameter relationships.

Importance The successful implementation of artificial intelligence (AI) in health care depends on its acceptance by key stakeholders, particularly patients, who are the primary beneficiaries of AI-driven outcomes. Objectives To survey hospital patients to investigate their trust, concerns, and preferences toward the use of AI in health care and diagnostics and to assess the sociodemographic factors associated with patient attitudes. Design, Setting, and Participants This cross-sectional study developed and implemented an anonymous quantitative survey between February 1 and November 1, 2023, using a nonprobability sample at 74 hospitals in 43 countries. Participants included hospital patients 18 years of age or older who agreed with voluntary participation in the survey presented in 1 of 26 languages. Exposure Information sheets and paper surveys handed out by hospital staff and posted in conspicuous hospital locations. Main Outcomes and Measures The primary outcome was participant responses to a 26-item instrument containing a general data section (8 items) and 3 dimensions (trust in AI, AI and diagnosis, preferences and concerns toward AI) with 6 items each. Subgroup analyses used cumulative link mixed and binary mixed-effects models. Results In total, 13 806 patients participated, including 8951 (64.8%) in the Global North and 4855 (35.2%) in the Global South. Their median (IQR) age was 48 (34-62) years, and 6973 (50.5%) were male. The survey results indicated a predominantly favorable general view of AI in health care, with 57.6% of respondents (7775 of 13 502) expressing a positive attitude. However, attitudes exhibited notable variation based on demographic characteristics, health status, and technological literacy. Female respondents (3511 of 6318 [55.6%]) exhibited fewer positive attitudes toward AI use in medicine than male respondents (4057 of 6864 [59.1%]), and participants with poorer health status exhibited fewer positive attitudes toward AI use in medicine (eg, 58 of 199 [29.2%] with rather negative views) than patients with very good health (eg, 134 of 2538 [5.3%] with rather negative views). Conversely, higher levels of AI knowledge and frequent use of technology devices were associated with more positive attitudes. Notably, fewer than half of the participants expressed positive attitudes regarding all items pertaining to trust in AI. The lowest level of trust was observed for the accuracy of AI in providing information regarding treatment responses (5637 of 13 480 respondents [41.8%] trusted AI). Patients preferred explainable AI (8816 of 12 563 [70.2%]) and physician-led decision-making (9222 of 12 652 [72.9%]), even if it meant slightly compromised accuracy. Conclusions and Relevance In this cross-sectional study of patient attitudes toward AI use in health care across 6 continents, findings indicated that tailored AI implementation strategies should take patient demographics, health status, and preferences for explainable AI and physician oversight into account.

Multiple myeloma (MM) frequently evades complete evaluation with 18 F-FDG-PET/CT due to variable hexokinase expression, leading to false-negative findings. 18 F-fluorocholine-PET/CT (FCH) targets membrane phospholipid synthesis and has been proposed as an alternative imaging strategy to address this limitation. In this single-center retrospective study, 35 adult MM patients underwent dual-tracer PET/CT within four weeks. Lesions were scored using Deauville-based criteria (IMPeTUs), and exploratory composite scores (hTepe and myPET) were calculated. Laboratory markers, including M-protein, free light chains, and bone marrow infiltration, were collected within four weeks of imaging. The cohort (22 men, 13 women; mean age 62.2 ± 10.9 years) included 19 patients at initial staging and 16 at restaging. FDG detected active disease in 49

99mTc-sestamibi uptake in renal masses was hypothetically related to the interplay between the mitochondrial content and cell membrane P-glycoprotein (MDR1) pump expression. A subtractive normalization of mitochondrial content model was proposed to predict how tumors will appear on 99mTc-sestamibi scintigraphy. We aimed to test this model and demonstrate the 99mTc-sestamibi uptake pattern in different renal pathologies. A preoperative 99mTc-sestamibi SPECT/CT scintigraphy was performed to 86 renal masses. On pathological examination cell membrane P-glycoprotein (MDR1) pump expression and mitochondrial content were determined. Mitochondrial staining scores were normalized by subtracting cell membrane P-glycoprotein (MDR1) immunostaining records from the noted mitochondrial staining scores. The subtractive normalization values ranged between -3/+3, with +3 indicating strong mitochondrial content and no cell membrane P-glycoprotein (MDR1) pump expression and -3 indicating the opposite. These values were analyzed in the light of 99mTc-sestamibi uptake. The majority of benign lesions (11/15) showed a subtractive normalization value of +2/+3, while the rest had 0/+1 value. The majority of malignant lesions (60/71) had value between -1/+1. 11 clear cell RCC cases showed a + 2/+3 value. 99mTc-sestamibi uptake correlated negligibly with subtractive normalization of mitochondrial content (Spearman correlation of 0.279, p = 0.009). This correlation was not able to explain either the positive 99mTc-sestamibi uptake in tumors with zero subtractive normalization value like chromophobe RCC lesions or the negative 99mTc-sestamibi uptake in tumors with positive subtractive normalization value like angiomyolipomas or oncocytic papillary RCC. The hypothesized interplay between mitochondrial content and cell membrane P-glycoprotein (MDR1) pump may not be enough to explain the molecular basis of 99mTc-sestamibi uptake by renal masses. Mitochondrial P-glycoprotein, cell membrane MRP transporters and the functionality of multidrug resistance transporters should be in the scope of future research regarding the kinetics of 99mTc-sestamibi in different pathologies.