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This document provides the new EANM guideline on radioiodine therapy of benign thyroid disease. Its aim is to guide nuclear medicine physicians, endocrinologists, and practitioners in the selection of patients for radioiodine therapy. Its recommendations on patients’ preparation, empiric and dosimetric therapeutic approaches, applied radioiodine activity, radiation protection requirements, and patients follow-up after administration of radioiodine therapy are extensively discussed.

Purpose To examine the relationship between the extent of disease determined by [ 68 Ga]PSMA-HBED-CC-PET/CT and the important clinical measures prostate-specific antigen (PSA), PSA doubling time (PSAdt) and Gleason score. Methods We retrospectively studied the first 155 patients with recurrent prostate cancer (PCA) referred to our university hospital for [ 68 Ga]PSMA-HBED-CC PET/CT. Results PET/CT was positive in 44 %, 79 % and 89 % of patients with PSA levels of ≤1, 1 – 2 and ≥2 ng/ml, respectively. Patients with high PSA levels showed higher rates of local prostate tumours ( p  < 0.001), and extrapelvic lymph node ( p  = 0.037) and bone metastases ( p  = 0.013). A shorter PSAdt was significantly associated with pelvic lymph node ( p  = 0.026), extrapelvic lymph node ( p  = 0.001), bone ( p  < 0.001) and visceral ( p  = 0.041) metastases. A high Gleason score was associated with more frequent pelvic lymph node metastases ( p  = 0.039). In multivariate analysis, both PSA and PSAdt were independent determinants of scan positivity and of extrapelvic lymph node metastases. PSAdt was the only independent marker of bone metastases ( p  = 0.001). Of 20 patients with a PSAdt <6 months and a PSA ≥2 ng/ml, 19 (95 %) had a positive scan and 12 (60 %) had M1a disease. Of 14 patients with PSA <1 ng/ml and PSAdt >6 months, only 5 (36 %) had a positive scan and 1 (7 %) had M1a disease. Conclusion [ 68 Ga]PSMA-HBED-CC PET/CT will identify PCA lesions even in patients with very low PSA levels. Higher PSA levels and shorter PSAdt are independently associated with scan positivity and extrapelvic metastases, and can be used for patient selection for [ 68 Ga]PSMA-HBED-CC PET/CT.

AimTo explore the dosimetric effect of substituting Lu-177 with Tb-161 in targeted radionuclide therapy (TRT) using the registered tracers DOTA-TATE and PSMA-617.MethodsUsing established kinetic data for [177Lu]Lu-DOTA-TATE and [177Lu]Lu-PSMA-617, radiation absorbed doses to typical tumour lesion as well as non-target tissues ([177Lu]Lu-DOTA-TATE: kidneys, spleen and liver, [177Lu]Lu-PSMA-617: kidneys, liver and salivary glands) were calculated for Lu-177 and Tb-161.ResultsFor both DOTA-TATE and PSMA-617, the substitution of Lu-177 with Tb-161 results in an increase in the delivered dose per unit of activity to tumour tissue by 40%. If an equivalent non-target delivered dose is strived for in order not to increase toxicity, based on kidney absorbed dose, 7400 MBq Lu-177 per cycle should be substituted with 5400 MBq Tb-161 for DOTA-TATE and 5300 MBq of Tb-161 for PSMA-617.ConclusionWhen substituting Lu-177 with Tb-161, activity conversion is necessary in order not to exceed non-target dose limits.

PurposeThe study aimed to provide a comprehensive bibliometric overview of the current scientific publications on fibroblast activation protein inhibitor (FAPI) positron emission tomography imaging and radionuclide therapy.MethodsA PubMed search was performed to identify all MEDLINE-indexed publications on FAPI imaging and radionuclide therapy. The last update was performed on 31 May 2022. An online database of this literature was created, and hierarchical topic-related tags were subsequently assigned to all relevant studies. Frequency analysis was used to evaluate the distribution of the following characteristics: first author’s country of origin, journal of publication, study design, imaging techniques and radiopharmaceutical used, histopathological correlation, the type of cancer, and benign disease/uptake types evaluated.ResultsA total of 294 relevant publications on original studies were identified, consisting of 209 (71%) case reports/series and 85 cohort studies (29%). The majority of studies focused on imaging topics, predominantly comparing uptake on FAPI-PET/CT with 2-[18F]FDG-PET/CT, anatomical imaging, and/or histopathology results. 68% of studies focused on malignancies, with gastro-intestinal cancer, hepato-pancreato-biliary cancer, mixed cancers/metastases, lung cancer, sarcoma, head and neck cancer, and breast cancer being the most frequently reported. 42% of studies focused on benign disease categories, with cardiovascular, musculoskeletal, HPB, head and neck, and IgG4-related disease as most common categories. 16/294 (5%) studies focused on radionuclide therapy, with preliminary reports of acceptable toxicity profiles, tumour activity retention, and suggestion of disease control.ConclusionFAPI research is rapidly expanding from diagnostic studies in malignancies and benign diseases to the first reports of salvage radionuclide therapy. The research activity needs to shift now from low-level-of-evidence case reports and series to prospectively designed studies in homogenous patient groups to provide evidence on how and in which clinical situations FAPI theranostics can be of added value to clinical care. We have provided an overview of current research topics to build upon.

Background Fatty acid synthase (FASN) is crucial to de novo long-chain fatty acid synthesis, needed to meet cancer cells’ increased demands for membrane, energy, and protein production. Methods We investigated FASN overexpression as a therapeutic and chemosensitization target in ovarian cancer tissue, cell lines, and primary cell cultures. FASN expression at mRNA and protein levels was determined by quantitative real-time polymerase chain reaction and immunoblotting and immunohistochemistry, respectively. FASN inhibition’s impact on cell viability, apoptosis, and fatty acid metabolism was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay, cell death detection enzyme-linked immunosorbent assay, immunoblotting, and 18  F-fluoromethylcholine uptake measurement, respectively. Results Relative to that in healthy fallopian tube tissue, tumor tissues had 1.8-fold average FASN protein overexpression; cell lines and primary cultures had 11-fold–100-fold mRNA and protein overexpression. In most samples, the FASN inhibitor cerulenin markedly decreased FASN expression and cell viability and induced apoptosis. Unlike concomitant administration, sequential cerulenin/cisplatin treatment reduced cisplatin’s half maximal inhibitory concentration profoundly (up to 54%) in a cisplatin-resistant cell line, suggesting platinum (re)sensitization. Cisplatin-resistant cells displayed lower 18  F-fluoro-methylcholine uptake than did cisplatin-sensitive cells, suggesting that metabolic imaging might help guide therapy. Conclusions FASN inhibition induced apoptosis in chemosensitive and platinum-resistant ovarian cancer cells and may reverse cisplatin resistance.

Background Gastropod-borne metastrongyloid lungworm infections are poorly understood despite their importance in both veterinary and human medicine. This study intends to assess the use of nuclear imaging with whole-body positron emission tomography and computed tomography to scan radiolabeled Angiostrongylus vasorum - and Crenosoma striatum first-stage larvae (L1) while migrating in vivo in the obligate mollusc intermediate hosts. Here, the giant African snail ( Lissachatina fulica ) was used as a novel animal model for lungworm-associated investigations, as this gastropod species is known to act as a natural obligate intermediate host in the tropics for various metastrongyloid lungworms, including the zoonotic-relevant Angiostrongylus cantonensis . Radiolabeled A. vasorum - and C. striatum L1 migration was visualized through nuclear imaging after L1 oral infection or injection. Methods Live L1 were collected through the standard Baermann funnel technique. After isolation and assessment of larval viability, collected A. vasorum - and C. striatum L1 were incubated with a radiolabeled glucose analogue, 18 F-fluordesoxyglucose. Thereafter, radiolabeled L1 were fed orally or injected into adult L. fulica , and in vivo scans were performed to visualize larval migration routes at different time points post infection through various gastropod organs/tissues. Results The most optimal incubation time of larvae and 18 F-fluordesoxyglucose was 30 min. After washing nonincorporated tracer, metastrongyloid L1 retained on average activity of 0.33 (0.103) KBq per larvae. This was the maximum activity achieved, and even longer incubation times, i.e., 60 and 120 min, did not exceed this value. The in vivo scans showed dispersal from the site of larval injection or feeding. Radiolabeled A. vasorum - or C. striatum L1 moved rapidly from the site of injection or the oral cavity with nonspecific accumulation in one or numerous gastropod organs at 30 min post infection. Conclusions This study concludes that radiolabeling of metastrongyloid L1 with 18 F-fluordesoxyglucose is achievable up to a level that can be detected in a scan of individual snails. Scanning L1 larvae in L. fulica at 60 min still represents larval migration. After 2 h, this study found that the migration is already widespread, and the activity is too low to be narrowed to a specific organ. Detailed in vivo scans of gastropods with not only higher infectious doses but also other radiolabeled tracers and longer observation periods might allow detection of either organ tropism or larval accumulation in certain mollusc tissues/organs for further development into infective stages. Graphical abstract

We aimed to identify differences in mutational status between follicular thyroid adenoma (FTA) and follicular thyroid cancer (FTC). The study included 35 patients with FTA and 35 with FTC. DNA was extracted from formalin-fixed paraffin-embedded (FFPE) samples from thyroidectomy. Next-generation sequencing (NGS) was performed with the 50-gene Ion AmpliSeq Cancer Hotspot Panel v2. Potentially pathogenic mutations were found in 14 (40%) FTA and 24 (69%) FTC patients (OR (95%CI) = 3.27 (1.22−8.75)). The number of mutations was higher in patients with FTC than FTA (p-value = 0.03). SMAD4 and STK11 mutations were present only in patients with FTA, while defects in FBXW7, JAK3, KIT, NRAS, PIK3CA, SMARCB1, and TP53 were detected exclusively in FTC patients. TP53 mutations increased the risk of FTC; OR (95%CI) = 29.24 (1.64–522.00); p-value = 0.001. FLT3-positivity was higher in FTC than in the FTA group (51.4% vs. 28.6%; p-value = 0.051). The presence of FLT3 and TP53 with no RET mutations increased FTC detectability by 17.1%, whereas the absence of FLT3 and TP53 with a presence of RET mutations increased FTA detectability by 5.7%. TP53 and FLT3 are candidate markers for detecting malignancy in follicular lesions. The best model to predict FTA and FTC may consist of FLT3, TP53, and RET mutations considered together.

Background Dynamic two-dimensional (2D) planar renal scintigraphy is a widely used imaging modality for evaluating renal function, though its anatomical and quantitative accuracy is limited by overlapping structures. Recent advancements in single photon emission computed tomography/computed tomography (SPECT/CT) technology employ a multi-detector cadmium-zinc-telluride (CZT) ring configuration. This eliminates the need for camera rotation around the patient, reducing acquisition time and enabling high temporal resolution dynamic three-dimensional (3D) imaging. This technology may be particularly beneficial for kidney transplant patients. Case presentation We present a case of a 44-year-old male who underwent dynamic SPECT/CT renal scintigraphy with impaired urinary excretion following post kidney transplantation. Conclusions Dynamic SPECT/CT using a 3D-ring CZT-based camera demonstrated added diagnostic value in the presented renal scintigraphy application.

Although with a standardized incidence of 0.54 cases per 100,000 persons, differentiated thyroid cancer (DTC) is a rare disease in children and adolescents, it nonetheless concerns ~1.4% of all pediatric malignancies. Furthermore, its incidence is rising. Due to the rarity and long survival of pediatric DTC patients, in most areas of treatment little evidence exists. Treatment of pediatric DTC is therefore littered with controversies, many questions therefore remain open regarding the optimal management of pediatric papillary thyroid cancer (PTC), and many challenges remain unsolved. In the present review, we aim to provide an overview of these challenging areas of patient and disease management in pediatric PTC patients. Data on diagnosis, surgery, radionuclide, and endocrine therapy are discussed, and the controversies therein are highlighted.

Objective Clinical and laboratory guidelines recommend thyroglobulin antibodies (TgAbs) measurement with every thyroglobulin (Tg) measurement for the follow-up of differentiated thyroid cancer (DTC) patients. However, no evidence exists on the need for perpetual TgAbs testing in patients who are TgAb-negative at baseline. Our study was carried out to evaluate the prevalence, the dynamic changes, and the clinical significance of TgAbs that appeared de novo during the follow-up of DTC patients who were TgAb-negative at baseline. Methods The data of DTC patients with negative pre-ablation TgAbs were reviewed retrospectively. The main characteristics of patients with both transient and sustained de novo TgAbs appearance were analyzed. DTC patients with persistently negative TgAbs served as controls. Results Among 119 patients with pre-ablation negative TgAbs, 14 cases (11.7%) with de novo TgAbs appearance (10 and 4 patients with a transient and sustained de novo TgAbs appearance, respectively) were detected. No differences in disease-free survival were observed in patients with de novo TgAbs appearance compared to controls. The TgAbs peak value was higher in patients with sustained de novo appearance compared to patients with transient de novo. Two of 14 patients with de novo TgAbs developed structural disease with concurrently detectable Tg in both cases. Conclusions Transient de novo TgAbs appearance is not infrequent during DTC patients’ follow-up, and it has no apparent clinical impact. Sustained de novo TgAbs appearance is rare and may predict structural recurrences; however, similar disease-free survival was observed in patients with sustained de novo TgAbs and TgAb-negative DTC patients.