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Purpose: We aimed to compare the diagnostic performance of 68Ga-FAPI-04 (FAPI) in comparison to 68Ga-DOTATATE (SSTR) PET/CT for patients presenting with recurrent medullary thyroid carcinoma (MTC)., Patients and Methods: Sixteen MTC patients with elevated calcitonin levels (>150 pg/mL) underwent FAPI and SSTR PET/CT. Two nuclear medicine physicians evaluated all images, categorizing lesions into locoregional metastases, mediastinal lymph nodes (LNs), liver, and bone metastases. SUVmax and tumor-to-background ratio were recorded. PET modalities were compared using the McNemar test. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FAPI and SSTR PET were calculated., Results: The cohort comprised 16 patients (50% female; mean age 50 ± 17 years). Median calcitonin and CEA levels were 6234 pg/mL and 17.3 ng/mL, respectively. In patient-based analysis, SSTR exhibited higher diagnostic sensitivity compared with FAPI (88% vs 81%), resulting a statistically significant difference (P = 0.004). Mean SUVmax and tumor-to-background ratio values were 10.3 and 5.35 for FAPI, and 9.7 and 11.9 for SSTR PET, respectively. In lesion-based analyses, FAPI demonstrated higher accuracy than SSTR for cervical LNs (91.9% vs 50%), mediastinal LNs (94.9% vs 54.4%), and liver metastases (57.4% vs 7.3%), respectively. Notably, 31% of patients (n = 5) with FAP-expressing liver lesions showed no uptake on SSTR imaging. MRI confirmed liver metastases in 3 of these patients; however, 2 FAP-expressing lesions were confirmed as hemangiomas. False-positive findings of DOTA primarily included reactive LNs and bone hemangiomas., Conclusions: FAPI PET presents promising outcomes in detecting metastases in recurrent MTC patients. Although its diagnostic performance matches SSTR on a per-patient basis, FAPI PET exhibits superior sensitivity and accuracy in lesion-based analyses, notably for liver and bone metastases., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The extent of the surgical treatment for Graves' disease (GD) has evolved from subtotal to total thyroidectomy. This study analyzes the extent of thyroidectomy for GD and its impact on recurrence and complications, focusing on the relationship between remnant thyroid tissue and recurrence in subtotal thyroidectomy, comparing our current approach with historic data spanning over three decades., Methods: A retrospective analysis of 427 GD patients who underwent surgery at a tertiary hospital from 1988 to 2022. Patients were categorized into total/near-total thyroidectomy (TT, n=302) and subtotal thyroidectomy (ST, n=125). The groups were compared for demographics, postoperative complications, and recurrent hyperthyroidism rates. ROC analysis determined the remnant cut-off value for recurrence in the ST group., Results: Age and sex were similar across groups. Recurrent hyperthyroidism was found in 8% of ST patients but none in the TT group (p<0.001). Transient hypoparathyroidism was higher in the TT group (16.9% vs. 0.8%; p<0.001). Persistent hypoparathyroidism and vocal cord paralysis rates were comparable. ST patients with recurrence had more remnant tissue (5.3±0.94 g vs. 3.4±1.34 g; p<0.01). The remnant tissue cut-off for predicting recurrence was 4 g (<4 g: 0%, ≥4 g: 17.8%; p<0.001)., Conclusion: Total thyroidectomy has lower recurrence rates than subtotal thyroidectomy without significantly increasing long-term complications. Remnant tissue larger than 4 g in subtotal thyroidectomy increases the risk of recurrence., Competing Interests: None declared., (© Copyright 2024 by The Medical Bulletin of Sisli Etfal Hospital.)

Abstract: Neuroblastoma is the most common malignancy in infants and the most common extracranial solid tumor accounting for approximately 6% of pediatric cancer. Although surgical intervention serves as the primary treatment for early-stage disease, advanced-stage cases necessitate a variety of oncologic therapeutic approaches, including 131I-MIBG and peptide receptor radionuclide therapy. Herein we report incidental pineal gland activity, represented in 68Ga-DOTATATE PET/CT (SSTR-PET) in 3 pediatric patients diagnosed with stage 4 neuroblastoma, related to the physiological distribution of radiopharmaceuticals., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: We present a case with systemic amyloidosis secondary to immunoglobulin light-chain amyloidosis (AL amyloidosis), which 18F-FDG PET/CT and 99mTc-PYP scintigraphy revealed amyloid deposition in the peritoneum, omentum, and mesentery. AL amyloidosis is characterized by the proliferation of clonal plasma cells and increased production and extracellular accumulation of immunoglobulin light chains, leading to organ malfunction. Even though AL amyloidosis can affect the gastrointestinal system, peritoneal involvement is rarely observed. PET/CT and SPECT/CT images showed moderate to slightly increased tracer uptake in affected organs., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: We aimed to compare the diagnostic performance of 68Ga-FAPI-04 (FAPI) in comparison to 68Ga-DOTATATE (SSTR) PET/CT for patients presenting with recurrent medullary thyroid carcinoma (MTC)., Patients and Methods: Sixteen MTC patients with elevated calcitonin levels (>150 pg/mL) underwent FAPI and SSTR PET/CT. Two nuclear medicine physicians evaluated all images, categorizing lesions into locoregional metastases, mediastinal lymph nodes (LNs), liver, and bone metastases. SUVmax and tumor-to-background ratio were recorded. PET modalities were compared using the McNemar test. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FAPI and SSTR PET were calculated., Results: The cohort comprised 16 patients (50% female; mean age 50 ± 17 years). Median calcitonin and CEA levels were 6234 pg/mL and 17.3 ng/mL, respectively. In patient-based analysis, SSTR exhibited higher diagnostic sensitivity compared with FAPI (88% vs 81%), resulting a statistically significant difference (P = 0.004). Mean SUVmax and tumor-to-background ratio values were 10.3 and 5.35 for FAPI, and 9.7 and 11.9 for SSTR PET, respectively. In lesion-based analyses, FAPI demonstrated higher accuracy than SSTR for cervical LNs (91.9% vs 50%), mediastinal LNs (94.9% vs 54.4%), and liver metastases (57.4% vs 7.3%), respectively. Notably, 31% of patients (n = 5) with FAP-expressing liver lesions showed no uptake on SSTR imaging. MRI confirmed liver metastases in 3 of these patients; however, 2 FAP-expressing lesions were confirmed as hemangiomas. False-positive findings of DOTA primarily included reactive LNs and bone hemangiomas., Conclusions: FAPI PET presents promising outcomes in detecting metastases in recurrent MTC patients. Although its diagnostic performance matches SSTR on a per-patient basis, FAPI PET exhibits superior sensitivity and accuracy in lesion-based analyses, notably for liver and bone metastases., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: This study aims to assess 68 Ga-Trivehexin PET/CT for detecting hyperfunctioning parathyroid tissue in comparison to [ 99m Tc]Tc-MIBI scintigraphy-SPECT/CT (MIBI scan) in patients with primary hyperparathyroidism (PHPT)., Methods: The cohort comprised 13 patients diagnosed with PHPT based on biochemical analyses, including serum calcium, phosphorus, and parathyroid hormone (PTH) levels. Each participant underwent cervical ultrasonography, MIBI scan, and 68 Ga-Trivehexin PET/CT imaging. Complementary 4D-CT and [ 18 F]fluorocholine PET/CT were conducted in 7 patients. Ten lesions of 7 patients underwent PTH wash-out (WO) procedure. 68 Ga-Trivehexin PET/CT findings were compared with other modalities and PTH-WO results., Results: Ten patients had sporadic PHPT, while 3 were diagnosed with MEN-1 syndrome-associated PHPT. One patient did not have any identifiable parathyroid lesion across the imaging modalities. On a patient-based analysis, MIBI scan and 68 Ga-Trivehexin PET/CT identified parathyroid lesions in 10 and 11 patients, respectively. However, 68 Ga-Trivehexin PET/CT detected 7 additional parathyroid lesions that were negative on the MIBI scan. Consequently, 17 lesions were identified and confirmed as hyperfunctioning parathyroid tissue through imaging, PTH-WO, or a combination of both modalities. In lesion-based evaluation, 68 Ga-Trivehexin identified 16 lesions compared to 10 by MIBI scan, resulting in a detection rate of 94.1% and 58.8%, respectively. Notably, in three patients who underwent [ 18 F]fluorocholine PET/CT, no lesions were detected; yet 68 Ga-Trivehexin PET/CT successfully identified parathyroid lesions in two of these patients., Conclusion: Our study provides the first evidence that 68 Ga-Trivehexin PET/CT can effectively identify hyperfunctioning parathyroid tissue with a high detection rate warranting further investigations to comprehensively explore its potential in PHPT management., (© 2024. The Author(s).)

Abstract: Amyloidosis is a misfolded protein deposition disorder within the extracellular matrix, leading to dysfunction in the affected organ. Primary amyloidosis manifests as AL and ATTR subtypes, wherein AL is associated with plasma cell dyscrasias. Herein we present a case of a patient who underwent investigation due to the presence of bilateral reticulonodular lung infiltrates, suggestive of miliary tuberculosis. 99m Tc-PYP scan revealed widespread radiotracer uptake in the lungs leading to diagnosis of AL amyloidosis., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This study assesses fibroblast activated protein inhibitor (FAPI) targeted PET/CT imaging against [ 18 F]FDG PET/CT (FDG PET) for detecting nodal involvement in head and neck squamous cell carcinoma (HNSCC), intending to improve diagnostic precision for metastatic lymph nodes and lay the groundwork for future investigations. Methods: Patients diagnosed with HNSCC were retrospectively enrolled. All patients underwent [ 68 Ga]Ga-FAPI04 PET/CT (FAPI PET) and FDG PET within 6 d. Primary tumor, lymph nodes, and tracer uptake were visually and quantitatively compared. The metastatic lymph nodes were evaluated using patient-and lesion-based analyses, with biopsy or postoperative histopathological examination as the reference. Results: The cohort includes 24 patients (17 men, 7 women; mean age 60 ± 11.8 years) who underwent FDG and FAPI PET for preoperative diagnostic workup or restaging due to known recurrence of HNSCC. Lesions included 24 primary tumors, 54 cervical lymph nodes, and 5 metastases. Primary tumors exhibited significant uptake on both PET modalities (median maximum standardized uptake value [SUV max ]: FDG 19.4 ± 11.6, FAPI 16.9 ± 4.6), with no statistically significant difference ( p > 0.5). For lymph nodes, FAPI and FDG PET showed median SUV max of 9.18 ± 6.77 and 9.67 ± 6.5, respectively. The patient-based analysis found FDG PET sensitivity at 88.2% and FAPI PET at 94.1%, with FAPI PET specificity significantly higher (85.7% vs. 42.8% for FDG PET). Lesion-based analysis revealed FAPI PET sensitivity and specificity at 84.2% and 93.7%, respectively, contrasting FDG PET's at 81.5% and 25%, respectively. Conclusion: This study underscores the efficacy of FAPI PET in detecting primary tumors in HNSCC. Furthermore, FAPI PET shows improved specificity over FDG PET for metastatic lymph nodes advocating further investigations for integrating FAPI PET into HNSCC clinical protocols for its enhanced precision in detecting metastatic lymph nodes.

Mutations in the transcription factors encoded by PHOX2B or LBX1 correlate with congenital central hypoventilation disorders. These conditions are typically characterized by pronounced hypoventilation, central apnea, and diminished chemoreflexes, particularly to abnormally high levels of arterial PCO 2 . The dysfunctional neurons causing these respiratory disorders are largely unknown. Here, we show that distinct, and previously undescribed, sets of medullary neurons coexpressing both transcription factors (dB2 neurons) account for specific respiratory functions and phenotypes seen in congenital hypoventilation. By combining intersectional chemogenetics, intersectional labeling, lineage tracing, and conditional mutagenesis, we uncovered subgroups of dB2 neurons with key functions in (i) respiratory tidal volumes, (ii) the hypercarbic reflex, (iii) neonatal respiratory stability, and (iv) neonatal survival. These data provide functional evidence for the critical role of distinct medullary dB2 neurons in neonatal respiratory physiology. In summary, our work identifies distinct subgroups of dB2 neurons regulating breathing homeostasis, dysfunction of which causes respiratory phenotypes associated with congenital hypoventilation.

Purpose: The aim of this study was to evaluate the potential role of [ 18 F]FDG positron emission tomography/computed tomography (PET/CT) in the characterization of thymic epithelial tumors (TETs). Materials and Methods: A total of 73 patients who underwent preoperative [ 18 F]FDG PET/CT were included in this study. Visual total score (VTS), maximum standard uptake values (SUV max ), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity index (HI) parameters were analyzed to investigate the prediction of histopathologic grade and advanced stage. Results: The cohort included 26 patients with low-grade thymoma (LGT), 36 patients with high-grade thymoma (HGT), and 11 patients with thymic carcinoma (TC). Ninety-one percent of TC had VTS >2, whereas 31% of LGT and 75% of HGT had VTS >2. SUV max , MTV, and TLG were statistically significantly higher in the TC group than in both thymoma and HGT. Using the cutoff value of 7.25 for SUV max , TC was differentiated from thymomas with 91% sensitivity and 74% specificity. TC had significantly lower HI values than thymomas. HI parameters showed good diagnostic ability to differentiate TC from thymoma and TC from HGT. SUV max , MTV, and TLG were significantly higher in advanced-stage disease than in early-stage disease. Conclusions: Visual and quantitative parameters can reliably predict both advanced disease and the grade of primary tumor in TETs. Therefore, as a promising metabolic imaging method, [ 18 F]FDG PET/CT makes important contributions to preoperative evaluation in routine clinical practice.

Purpose: This study evaluated the effect of an increase in the time interval between hepatic intra-arterial injection of 99m Tc-macroaggregated albumin (MAA) and hepatic artery perfusion scintigraphy (HAPS) on the lung shunt fraction (LSF) and perfused volume (PV) calculations in the treatment planning of selective internal radiation therapy (SIRT). Methods: The authors enrolled 51 HAPS sessions from 40 patients diagnosed with primary or metastatic liver malignancy. All patients underwent scan at the first and fourth hour after hepatic arterial injection of 99m Tc-MAA. Based on single-photon emission computed tomography images, LSF values were measured from each patient's first and fourth hour images. PV1 and PV4 were also calculated based on three-dimensional images using 5% and 10% cutoff threshold values and compared with each other. Results: The authors found that the median of LSF4 was statistically significantly higher than LSF1 (3.05 vs. 4.14, p  ≤ 0.01). There was no statistically significant difference between PV1 and PV4 on the 10% ( p  = 0.72) thresholds. Conclusions: LSF values can be overestimated in case of delayed HAPS, potentially leading to treatment cancellation due to incorrectly high results in patients who could benefit from SIRT. Threshold-based PV values do not significantly change over time; nevertheless, keeping the short interval time would be safer.

Pulmonary arterial hypertension (PAH) is driven by pathologies associated with increased metabolism such as pulmonary revascularization, vasoconstriction and smooth muscle cell proliferation in pulmonary artery wall. 18-fluorodeoxyglucose positron emission tomography (18FDG-PET) is an imaging technique sensitive to glucose metabolism and might be considered as a non-invasive method for diagnosis due to significant role of inflammation in idiopathic pulmonary artery hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The present study aimed to investigate the role of PET/CT imaging of patients with IPAH and CTEPH as an alternative diagnosis method. Demographic characteristics, FDG uptake in lungs, pulmonary artery and right ventricle (RV) of 17 patients (10 IPAH, 7 CTEPH), and 30 controls were evaluated. PET scanning, 6-min walk test, pro-BNP level, right heart catheterization of patients were performed both at the onsert and after 6-month PAH specific treatment. IPAH and CTEPH patients had significantly higher left lung FDG ( p  = 0.006), right lung FDG ( p  = 0.004), right atrial (RA) FDG ( p  < 0.001) and RV FDG ( p  < 0.001) uptakes than controls. Positive correlation was detected between the RV FDG uptake and the mean pulmonary artery pressure (mPAP) ( r  = 0.7, p  = 0.012) and between the RA FDG uptake and the right atrial pressure (RAP) ( r  = 0.5, p  = 0.02). Increased RV FDG and RA FDG uptakes predicts the presence of pulmonary hypertension and correlates with mPAP and RAP, respectively, which are important indicators in the prognosis of PAH. Further studies are required whether FDG PET imaging can be used to diagnose or predict the prognosis of pulmonary hypertension., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Purpose: We aimed to investigate the role of [ 68  Ga]Ga-FAPI-04 PET/CT and uptake patterns of primary and metastatic lesions in patients with renal cell carcinoma (RCC)., Methods: Twenty patients with a suspicious lesion considered primary renal malignancy or a history of RCC were included in our study. Two patients were excluded from further analyses due to other confirmed malignancies. Six patients were newly diagnosed, while the indication of 12 patients was restaging. All patients underwent [ 68  Ga]Ga-FAPI-04 and [ 18 F]F-FDG PET/CT. SUVmax and tumor-to-background ratio (TBR) of primary (n = 7) and local recurrent lesions (n = 6) and lymph node (n = 26), lung (n = 32), bone (n = 5), and other metastases (n = 14) were compared between the two tracers., Results: We detected 90 lesions in 18 patients with varying FAPI and FDG uptake values on both PET/CT. The median TBR of FAPI-PET/CT of all lesions was higher than TBR of FDG-PET/CT with statistically significance (5.6 vs. 2.1, p < 0.001). In primary and recurrent lesions, the median SUVmax, TBR, and tumor volume on FAPI-PET/CT were higher than FDG-PET/CT. The median SUVmax of lung lesions on FAPI-PET/CT was statistical significantly higher than FDG-SUVmax (3.8 vs. 1.8, p = 0.02). The median of FAPI-SUVmax on primary lesions was lower in the early stage based on TNM compared to the advanced stage. FAPI-SUVmax in 49% of all lesions were SUVmax ≥ 6, and 13% were SUVmax ≥ 10. In patient-based analyses, seven patients (39%) had at least one lesion with FAPI-SUVmax ≥ 10; 12 patients (67%) had at least one lesion with FAPI-SUVmax ≥ 6., Conclusion: This study showed the potential utility of [68 Ga]Ga-FAPI-04 PET/CT showing promising results in RCC. We have presumed that FAPI-PET/CT may be performed for complementary imaging modality providing prognosis and possibility of theranostic application in selected patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We aimed to investigate the potential of [ 68 Ga]Ga-FAPI-04 PET/CT as an alternative diagnostic and theranostic tool in well-differentiated NETs refractory to [ 177 Lu]Lu-DOTATATE therapy., Methods: Patients who received at least two cycles of [ 177 Lu]Lu-DOTATATE therapy for metastatic NETs and progressed under treatment were included. All patients had performed [ 68 Ga]Ga-DOTATATE and [ 68 Ga]Ga-FAPI-04 PET/CT within 3 weeks. The number of PET-positive lesions related to NETs and tumor sites was documented. Mann-Whitney U and chi-square tests were used to compare SUVmax levels of tracers and the number of detected metastases., Results: Twelve patients (7 male, 5 female) who met the eligibility criteria were included in the study. Ten patients had grade 1-2 NET of various origins, and two had paraganglioma and pheochromocytoma. One hundred ninety-eight of 230 lesions (86%) were SSTR positive with a median SUVmax of 16.6 (2.2-76.5), and 88 of 230 lesions (38.2%) were [ 68 Ga]Ga-FAPI-04 positive with a median SUVmax of 5.1 (2.3-21). Median SUVmax level and detected number of tumors were significantly higher in [ 68 Ga]Ga-DOTATATE PET/CT (p=<0.001). [ 68 Ga]Ga-FAPI-04 PET/CT was completely (n:2) or almost completely (n:3) negative in 5 (42%) patients. Two (17%) patients had flip-flop SSTR/FAPI uptake in tumors. In four patients (33%), tumor uptake or the number of PET-positive lesions was inferior in [ 68 Ga]Ga-FAPI-04 PET/CT. In only one patient (8%), tumor uptakes were higher in [ 68 Ga]Ga-FAPI-04 PET/CT. Low-dose [ 177 Lu]Lu-FAPI-46 dosimetry was performed on the FAPI-dominant patient; absorbed radiation doses per GBq were 1.26 Gy, 0.36 Gy, 0.32 Gy, and 0.2 Gy for kidneys, liver, spleen, and total body, respectively. The mean absorbed dose per GBq was 0.33 Gy for liver mass and 0.41 Gy for metastatic lymph nodes., Conclusion: Our preliminary results demonstrated that [ 68 Ga]Ga-FAPI-04 PET/CT mainly failed in well-differentiated NETs refractory to [ 177 Lu]Lu-DOTATATE therapy and had a limited role as an alternative diagnostic or theranostic agent. Further investigations with a larger patient population are required to determine the impact of [ 68 Ga]Ga-FAPI-04 PET/CT on NETs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of this study is to review the clinical and laboratory characteristics, diagnostic and treatment modalities of tumor-induced osteomalacia (TIO) cases managed in a single center., Material Methods: Demographic and clinical features, biochemical findings, diagnostic procedures, treatment modalities, and outcomes of nine patients who had the diagnosis of TIO were reviewed retrospectively., Results: Mean age of the study group (F/M: 4/5) was 45.8 ± 10.8 years, and mean time from the onset of symptoms to diagnosis was 4.7 ± 2.8 years. The clinical manifestations were muscle weakness and difficulty in walking (8/9), hip pain (3/9), multiple fractures (2/9), stress fracture (2/9). Mean plasma phosphorus concentration was 1.28 ± 0.4 mg/dl at presentation. We performed radionuclide imaging modalities (18F-FDG PET/CT, Ga68-DOTATATE PET/CT, octreotide scintigraphy) in seven of nine patients, and tumor was detected in all. Lower extremity (n = 6; %67), head region (n = 2; %22) and thorax (n = 1; %11) were the tumor locations of our cases. Eight patients underwent surgery and remission was achieved postoperatively in all of the operated patients and plasma phosphorus level normalized in 4 ± 2 days. Pathological examination revealed mesenchymal tumors with different subtypes. Recurrence occurred in three patients at 13 ± 10.5 months after the first surgery. Two patients were reoperated and radiotherapy was also performed in one of them., Conclusion: Hypophosphatemia necessitates careful evaluation for the etiology. TIO is one of the important causes of adult-onset hypophosphatemic osteomalacia. Diagnosis of TIO is essential because the laboratory and clinical findings resolve after appropriate treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: A 69-year-old woman with breast cancer underwent 18 F-FDG PET/CT because of the increased CA-15-3 level. 18 F-FDG PET/CT showed multiple hypermetabolic lymph nodes (LNs) in the neck and mediastinum. The patient was also referred for 68 Ga-fibroblast activation protein inhibitor (FAPI) 04 PET/CT for further evaluation. However, 18 F-FDG-avid LNs were FAPI-negative on 68 Ga-FAPI-04 PET/CT. Supraclavicular LN biopsy confirmed the metastasis of breast cancer. Recent reports have focused on the potential of FAPI PET imaging in breast cancer; however, this case highlights that false-negative 68 Ga-FAPI-04-PET/CT findings should also be considered while evaluating metastatic spread., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/CT is an emerging imaging modality with high sensitivity and high tumor-to-background ratio in various cancers including in the head and neck regions. The authors present 2 cases of adenoid cystic carcinoma who underwent 68 Ga-FAPI-04 and 18 F-FDG PET/CT. Locoregional recurrence has been detected more precisely in the first case with 68 Ga-FAPI-04. In the second case, 68 Ga-FAPI-04 outperformed 18 F-FDG in the number of lesions and demonstrated intense FAP uptake on widespread metastases, which could provide a treatment option as a theranostic concept. These cases highlight that 68 Ga-FAPI-04 PET/CT may be useful for detecting local recurrence and metastases and help select patients for radionuclide treatments targeting cancer-associated fibroblasts., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: We present the 68 Ga-DOTATATE and 68 Ga-FAPI (fibroblast activation protein inhibitor) PET/CT findings of a 61-year-old man diagnosed with atypical World Health Organization grade II multiple meningiomas. The patient has been stable for 2 years following multiple surgeries and external radiotherapy because of recurring disease until he recently described frequent headaches, and a follow-up examination confirmed new meningioma lesions on MRI. However, the patient was inoperable and was referred for 68 Ga-DOTATATE PET/CT to determine eligibility for salvage peptide receptor radionuclide therapy. He also underwent fibroblast activation protein-targeted imaging using 68 Ga-FAPI04 PET/CT, which revealed heterogeneous, low to mild fibroblast activation protein expression across multiple meningioma lesions., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Papillary renal cell cancer is a rare malignancy with limited treatment options in the advanced stage of the disease. We present the case of a 62-year-old man with progressive left-sided papillary renal cell carcinoma who underwent 68 Ga-FAPI (fibroblast activated protein inhibitor)-04 and 18 F-FDG PET/CT imaging. 68 Ga-FAPI-04 PET/CT demonstrated variable FAP expression in all metastatic lesions detected by 18 F-FDG PET/CT, including multiple lymph nodes, bone, and thyroid. This case highlights that FAP-targeted imaging can be a promising modality for diagnostic and theranostic use in papillary renal cell carcinoma., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: We assessed the feasibility of SPECT/CT lymphoscintigraphy ( 99m Tc-nanocolloid) method to simplify and improve targeted axillary dissection of clipped axillary lymph node (axLN) after neoadjuvant chemotherapy (NAC) in initially node-positive breast cancer., Patients and Methods: Fifteen patients who had clip placement to biopsy-confirmed axLN metastasis due to clinically node-positive breast cancer before NAC and underwent SPECT/CT lymphoscintigraphy for surgery after NAC were included into the study. SPECT/CT lymphoscintigraphy was performed to localize the clipped node and to assess if the clipped lymph node (LN) had 99m Tc-nanocolloid uptake or not. In case the clipped node had no uptake on SPECT/CT, the patient was referred to wire-guided localization procedure. Blue dye was also injected for dual mapping of sentinel LN biopsy., Results: All patients had only ipsilateral axLN metastasis. SPECT/CT lymphoscintigraphy showed that clipped LNs were radioavid in 12 of 15 patients (80%). Clipped LNs were not blue-stained in 5 patients (33.3%), and in 2 of them, clipped LNs were radioavid in SPECT/CT. Wire-guided localization was required in only 3 patients (20%) for nonradioavid/blue-stained clipped LNs. Removal of the clipped nodes was confirmed in all cases with a success rate of 100% by specimen graphy., Conclusion: SPECT/CT lymphoscintigraphy seems feasible to determine the clipped LNs intraoperatively without requiring additional invasive methods in most of the patients. This technique simplifies and improves targeted axillary dissection of the clipped axLNs after NAC in initially node-positive breast cancer and can be adapted to clinical practice with further investigations., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aim: Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC). Circulating cell-free DNA (cfDNA) methylation of tumor suppressor genes are emerging potential biomarkers in HCC. We aimed to evaluate the cfDNA methylation status of RASSF1 and CDKN2AIP genes in patients with liver cirrhosis (LC) with or without HCC caused by HBV., Materials and Methods: A total of 47 patients with HBV cirrhosis were included in the study. Patients were divided into two groups: HCC and LC (HCC+LC, n=22) and HBV cirrhosis only (LC, n=25). cfDNA was isolated from the plasma samples of the patients. Methylation analysis was performed for RASSF1 and CDKN2AIP genes., Results: Mean methylation percentage of CDKN2AIP gene was 0.001±0.004% in the HCC+LC group and 0.008±0.004 % in the LC only group. The mean methylation percentage of RASSF1 gene was 5.1±16.1% in the HCC+LC group and 9.7±25.9% in the LC only group. The methylation rate of CDKN2AIP was significantly lower in the HCC+LC group (p=0.027). A positive correlation was found with the absence of cfDNA methylation of CDKN2AIP gene in the presence of HCC (R=0.667, p=0.018)., Conclusion: cfDNA methylation of CDKN2AIP and RASSF1 genes may provide important diagnostic information regarding the development of HCC in the setting of HBV cirrhosis., Competing Interests: The authors have no conflict of interest to declare., (© Copyright 2022 by Hepatology Forum.)

Purpose: This study was set out to analyze the efficacy and safety of 177 Lu-PSMA-617 (LuPSMA) treatment in metastatic castration-resistant prostate cancer (mCRPC) patients., Patients and Methods: Progressive mCRPC patients who received at least 1 cycle of LuPSMA therapy were evaluated retrospectively. Demographic, clinic, and histopathological data were documented. Treatment efficacy was determined based on biochemical response criteria (Prostate Cancer Clinical Trial Working Group 3), and toxicity rates were defined based on CTCAE v4.03. The prognostic significance of laboratory/clinical data and 68 Ga-PSMA PET/CT quantitative results were analyzed using SPSS Version 24.0., Results: One hundred patients (median prostate-specific antigen [PSA] level, 75.7 ng/mL) who met the eligibility criteria were identified. The median number of cycles received per patient was 3 (range, 1-9). After the first cycles of LuPSMA, biochemical partial response, biochemical stable disease, and biochemical progressive disease were observed in 31%, 36%, and 33% of patients, respectively. Any PSA decline was determined in 60% of patients. After the fourth cycle of treatment, biochemical partial response, biochemical stable disease, and biochemical progressive disease were defined in 48%, 26%, and 26% of patients, respectively. The median overall survival (OS) from the first cycle of LuPSMA was 14 months. Patients who had any PSA response after the first cycle had significantly longer OS than nonresponders (median OS: 17 vs 9 months; P ≤ 0.001). Total PSMA-derived tumor volume ( P = 0.004), total PSMA activity per lesion ( P = 0.01), PSA ( P = 0.007), alkaline phosphatase ( P = 0.002), lactate dehydrogenase ( P < 0.001), and hemoglobin ( P < 0.001) were significant prognostic factors for OS in univariate Cox regression analysis., Conclusions: LuPSMA therapy is a favorable treatment for mCRPC with remarkable therapeutic efficacy and low toxicity rates, even in progressive disease under standard therapies. Baseline PSMA-based tumor burden, PSA, alkaline phosphatase, lactate dehydrogenase, and hemoglobin were significant predictors of OS and can be useful for selection of the best candidate for LuPSMA therapy., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Split renal function (SRF) can be measured by using several methods in 99m Tc-DMSA scintigraphy. Geometric mean (GM) based methods derived from planar images(2D) have been used for several years, besides; 3D-methods were also reported as an option for assessment of SRF. The purpose of this study to compare 2D and 3D methods for calculation of SRF in pediatric and adult patients., Methods: We evaluated 212 patients, underwent both planar and SPECT 99m Tc-DMSA scintigraphy.2D-SRFs were calculated by GM without background correction (SRFnobcg), GM with background correction in crescent formation from lower lateral borders (SRFcres), and GM with background correction in circumferential formation, including the whole kidney surroundings (SRFcirc). In 3D settings, SRF was measured with SPECT (SRFspect). Paired t-test was used to compare the mean SRFs of each group. Bland-Altman method was used as an agreement method for each method. Analyses were performed based on left kidney SRFs., Results: In comparison of 2D and 3D methods, SRFspect was significantly different from SRFnobcg and SRFcres (p=<0.001) but not from SRFcirc (p = 0.155) in all patients. Similar results were found for patients with high creatinine level, SRFcirc and SRFspect were not significantly different (p = 0.317), while significant differences were found between SRFspect and SRFnobcg/SRFcres (p=<0.001).On the other hand, all 2D-methods showed statistical differences (p=<0.001-0.026) from 3D-method in pediatric patients. Bland-Altman-plot demonstrated that SRFcirc underestimated the poor functioning kidneys., Conclusion: SRFcirc can be used in measurement of SRF in adult patients with normal functioning kidneys in busy clinics. However, SRFspect provides more accurate results and suggested particularly for pediatric patients and poor functioning kidneys., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Breathing (or respiration) is a complex motor behavior that originates in the brainstem. In minimalistic terms, breathing can be divided into two phases: inspiration (uptake of oxygen, O 2 ) and expiration (release of carbon dioxide, CO 2 ). The neurons that discharge in synchrony with these phases are arranged in three major groups along the brainstem: (i) pontine, (ii) dorsal medullary, and (iii) ventral medullary. These groups are formed by diverse neuron types that coalesce into heterogeneous nuclei or complexes, among which the preBötzinger complex in the ventral medullary group contains cells that generate the respiratory rhythm (Chapter 1). The respiratory rhythm is not rigid, but instead highly adaptable to the physic demands of the organism. In order to generate the appropriate respiratory rhythm, the preBötzinger complex receives direct and indirect chemosensory information from other brainstem respiratory nuclei (Chapter 2) and peripheral organs (Chapter 3). Even though breathing is a hard-wired unconscious behavior, it can be temporarily altered at will by other higher-order brain structures (Chapter 6), and by emotional states (Chapter 7). In this chapter, we focus on the development of brainstem respiratory groups and highlight the cell lineages that contribute to central and peripheral chemoreflexes., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Abstract: Herein we present 2 mCRPC (metastatic castration-resistant prostate cancer) patients who underwent 68Ga-PSMA PET/CT for PSMA-targeted radioligand therapy eligibility. Prior studies have noted aggressive clinical behavior and poor prognosis associated with discordant FDG positivity and low PSMA expression. Accordingly, the patients also underwent 18F-FDG PET/CT, which revealed intratumoral heterogeneity. Therefore, an additional PET/CT targeting fibroblast activation proteins (FAPs) using 68Ga-FAPI-04 was performed to assess the potential for an FAP-targeted therapy. This report highlights the theranostic potential of FAP imaging in mCRPC, particularly in patients with heterogeneous tumor phenotypes., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Herein, we present a 72-year-old woman with metastatic thymic carcinoma, referred for salvage peptide receptor radionuclide therapy with 177Lu-DOTATATE after completing all treatment options according to current clinical practice and guidelines. However, the patient was not eligible for 177Lu-DOTATATE peptide receptor radionuclide therapy and underwent 68Ga-FAPI04 PET/CT to assess the potential for a FAP-targeted therapy., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Prostate-specific membrane antigen (PSMA)-targeted therapies are among the current promising treatments. We present our preliminary results on the use of 225Ac-PSMA therapy in patients with metastatic castration-resistant prostate cancer as a single center., Methods: Twelve advanced stage metastatic castration-resistant prostate cancer patients who received 225Ac-PSMA therapy were recruited in this retrospective study. Patients were treated with 225Ac-PSMA therapy every 8 weeks, and prostate-specific antigen (PSA) response was analyzed. Meanwhile, overall survival (OS) and progression-free survival (PFS) were estimated. Hematological and nonhematological adverse effects were recorded before and at 8 weeks after the last treatment cycle., Results: In total, 25 cycles of 225Ac-PSMA were administered to 12 patients. The pretreatment median PSA level was 129 ng/mL. After the first cycle of therapy, any PSA response was observed in 9 of 12 patients, whereas 6 of them had biochemical response of >50%. Four of 12 patients reached the best PSA response after the first treatment cycle, whereas 3 patients after the second and 2 patients after the third cycle. The median PFS and OS were 4 and 10 months, respectively. For patients with any PSA response after the first cycle, OS was found to be higher despite without any statistical significance (10 vs 4 months; P = 0.301) when compared with the nonresponsive group. No significant difference was encountered in terms of adverse effect in the pretreatment and posttreatment era., Conclusions: Our preliminary results are encouraging, especially patients who had PSA response after the first cycle of 225Ac-PSMA therapy., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study investigates the prognostic value of 68 Ga-Pentixafor PET/CT using PET-derived quantitative in multiple myeloma (MM) patients with suspected recurrence in comparison to 18 F-FDG PET/CT and clinical data., Methods: Twenty-four MM patients with suspicion for relapse who underwent 68 Ga-Pentixafor and 18 F-FDG PET/CT were retrospectively evaluated. Total bone marrow glycolysis for 18 F-FDG (TBM FDG ) and total bone marrow uptake for 68 Ga-Pentixafor PET/CT (TBM CXCR4 ) were calculated using whole-body metabolic tumor burden obtained by dedicated software (MIM 7.0.6). The patients were followed for 19-24 months, and the association of PET-derived quantitative data with overall survival (OS) was analyzed., Results: 68 Ga-Pentixafor PET/CT was positive in 17 patients, of which 13 were also positive on 18 F-FDG PET/CT, whereas 7 patients were negative on both scans. The positive rate of 68 Ga-Pentixafor and 18 F-FDG PET/CT on a patient-based approach was 70.8% and 54.1%, respectively. 68 Ga-Pentixafor positivity was significantly associated with OS (p = 0.009), and 18 F-FDG positivity was at the margin of statistical significance (p = 0.056). TBM CXCR4 and TBM FDG were negatively correlated with OS (r = -0.457, p = 0.025 and r = -0.617, p = 0.001, respectively). The OS was negatively correlated with beta-2-microglobulin levels (r = -0.511, p = 0.01) and CRAB score (r = -0.592, p = 0.002) as an indicator of the end-organ disease, which confirmed these results. Serum beta-2-microglobulin levels and CRAB score were also correlated with TBM CXCR4 (r = 0.442, p = 0.039 and r = 0.573, p = 0.003, respectively) and TBM FDG (r = 0.543, p = 0.009 and r = -0.424, p = 0.003, respectively)., Conclusion: 68 Ga-Pentixafor PET/CT positivity is a negative prognostic factor in the survival outcome of MM patients. Complementary 68 Ga-Pentixafor PET/CT has the potential to overcome 18 F-FDG PET/CT limitations and helps a more precise risk stratification., (© 2021. The Japanese Society of Nuclear Medicine.)

Objectives: This study is set out to estimate the radiation-absorbed doses to normal organs and tumor tissue using low-dose 177Lu-FAPI04 dosimetry to determine the safety and theranostic potential of fibroblast activation protein-targeted radionuclide therapy., Patients and Methods: Four patients with metastatic advanced-stage cancer were administered low-dose 177Lu-FAPI04 for dosimetry measurements. Data acquisition for dosimetry of normal organs and tumors was performed by whole-body and 3D SPECT/CT imaging at 4, 24, 48, and 96 hours after administering 177Lu-FAPI04. Blood samples were drawn at 5, 15, 30, 60, 60, 120, and 180 minutes, and at 24, 48, and 96 hours for bone marrow dosimetry calculations., Results: Mean absorbed doses per megabecquerel were 0.25 ± 0.16 mGy (range, 0.11-0.47 mGy), 0.11 ± 0.08 mGy (range, 0.06-0.22 mGy), and 0.04 ± 0.002 mGy (range, 0.04-0.046 mGy) for kidneys, liver, and bone marrow, respectively. The respective maximum estimated amount of radioactivity to reach radiation-absorbed dose limits were 120.9 ± 68.6 GBq, 47.5 ± 2.8 GBq, 397.8 ± 217.1 GBq, and 52.4 ± 15.3 GBq for kidneys, bone marrow, liver, and total body. The mean absorbed dose per megabecquerel was 0.62 ± 0.55 mGy for bone metastases, 0.38 ± 0.22 mGy for metastatic lymph nodes, 0.33 ± 0.21 mGy for liver metastases, and 0.37 ± 0.29 for metastatic soft tissue. The maximum absorbed dose in a tumor lesion was 1.67 mGy/MBq for bone, 0.6 mGy/MBq for lymph node, 0.62 mGy/MBq for liver, and 1 mGy/MBq for soft tissue., Conclusions: The mean absorbed dose to organs at risk with 177Lu-FAPI04 is reasonably low, allowing for low tumor-absorbed dose rates by administering a higher dose. Further research on optimizing therapeutic efficacy and using alternative radioisotopes is necessary, along with an individualized dosimetric approach., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Somatostatin receptor (SSTR) imaging with 68Ga-labeled somatostatin analogs has been used for many tumors with high SSTR expression. Increased uptake mostly depends on the SSTR status of tumors; however, false-positive uptake can be demonstrated in benign diseases or other malignancies because of the increased SSTR expression. We present a case of a 50-year-old man with increased SSTR activity on cervical lesion located in internal jugular chain in 68Ga-DOTATATE PET/CT, which was performed for suspicion of paraganglioma. Biopsy revealed lymph node metastasis of squamous cell carcinoma other than paraganglioma. 18F-FDG PET/CT showed primary malignancy on larynx and lymph node metastasis, which were correlated surgically., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: We investigated the role of PSMA-derived tumor burden in predicting docetaxel (DTX) therapy response in metastatic castration-resistant prostate cancer (mCRPC)., Methods: Fifty-two mCRPC patients who received at least six cycles of DTX as the first-line treatment following 68 Ga-PSMA PET/CT were enrolled in this retrospective study. Total PSMA-derived tumor volume (TV-PSMA) and total lesion PSMA activity (TL-PSMA) were derived from metastatic lesions. A ≥ 50% decline in PSA was defined as a response; a ≥ 25% increase in PSA was defined as progression. Univariate/multivariate logistic and cox regression analyses were performed to predict PSA response, OS, and TTP., Results: Twelve (23%) patients had PSA progression after chemotherapy, while 40 patients (77%) achieved a PSA response. On univariate analysis, a significant association was found between TV-PSMA (p = 0.001), TL-PSMA (p = 0.001), pre-PSA (p = 0.012), LDH (p = 0.003), Hg (p = 0.035), and PSA response to DTX. High TV-PSMA (> 107 cm 3 ) (p = 0.04) and high LDH (> 234 U/L) (p = 0.017) were 8.2 times and 12.2 times more likely for DTX failure in multivariate regression analyses. The median TTP was 16 months, and the median OS was not reached. Patients with high TV-PSMA (p = 0.017), high TL-PSMA (> 1013 cm 3 ) (p = 0.042), high age (> 70 years) (p = 0.016), and high LDH (p ≤ 0.001) had significantly shorter OS, while only high TV-PSMA (p = 0.038) and high age (p = 0.006) were significantly related with shorter TTP. High TV-PSMA (p = 0.017) and high age (p = 0.01) were significant predictors for shorter OS, while only high age (p = 0.006) was a significant predictor for shorter TTP in multivariate analysis., Conclusion: Patients with high TV-PSMA had a significantly higher risk for DTX failure. PSMA-based tumor burden prior to DTX therapy seems to be a reliable predictive tool for survival in mCRPC patients.

Abstract: We present a case of a 55-year-old man with a history of poorly differentiated metastatic thyroid cancer, which is rare and shows aggressive behavior. The patient had radioactive iodine-negative multiple metastasis on 18F-FDG PET/CT, therefore 68Ga-DOTATATE and 68Ga-PSMA PET/CT were performed whether an opportunity exist for DOTATATE or PSMA-directed radionuclide therapy. Different patterns of tumoral uptakes were detected on 18F-FDG, 68Ga-DOTATATE, and 68Ga-PSMA PET/CT, as a demonstration of tumor heterogeneity., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The mature cerebellum controls motor skill precision and participates in other sophisticated brain functions that include learning, cognition, and speech. Different types of GABAergic and glutamatergic cerebellar neurons originate in temporal order from two progenitor niches, the ventricular zone and rhombic lip, which express the transcription factors Ptf1a and Atoh1, respectively. However, the molecular machinery required to specify the distinct neuronal types emanating from these progenitor zones is still unclear. Here, we uncover the transcription factor Olig3 as a major determinant in generating the earliest neuronal derivatives emanating from both progenitor zones in mice. In the rhombic lip, Olig3 regulates progenitor cell proliferation. In the ventricular zone, Olig3 safeguards Purkinje cell specification by curtailing the expression of Pax2, a transcription factor that suppresses the Purkinje cell differentiation program. Our work thus defines Olig3 as a key factor in early cerebellar development., Competing Interests: EL, AR, JS, MH, AS, EE, FB, EI, SB, SJ, VT, LH No competing interests declared, (© 2021, Lowenstein et al.)

Objective: This study sets out to evaluate patients with increased uptake in breast lesions on 68 Ga-DOTATATE PET/CT (DOTA PET) and determine the clinical significance of somatostatin receptor (SSTR) positive breast lesions., Methods: We retrospectively evaluated all patients with increased SSTR uptake in breast lesions on DOTA PET. Patients with physiological (e.g., lactation) or normal variant breast uptake (e.g., mild diffuse glandular uptake) were excluded. The maximum standard uptake value (SUVmax) was calculated using a manually drawn region of interest in the most intense uptake of breast lesions. All lesions were correlated with breast imaging, including mammography and ultrasonography. Histopathological correlation was performed if the lesion was suspicious for malignancy. Lesions were followed up radiologically (1-8 years)., Results: Out of 1573 retrospectively analyzed DOTA PET scans, the incidence of SSTR + breast lesions was measured as 1.1% (n = 18); however, 4 of 18 patients were excluded due to the lack of final diagnosis of lesions. The median age was 35 (range 14-58 years), and all patients were female. The median SUVmax of SSTR + breast lesions was 5.2 (range 1.5-12.6) for a total of 14 patients. Twelve patients had a single SSTR + breast lesion, while 2 patients had multiple SSTR + lesions on bilateral breasts. In 6 patients, single SSTR + lesions were considered as fibroadenoma; in 2 patients, multiple SSTR + lesions were considered as metastases of NET, based on correlative breast imaging. In 6 patients, histopathological confirmation was needed for the final diagnosis. Histopathologic findings confirmed fibroadenoma in 4 patients by biopsy, in 1 patient with surgical removal of the lesion. The last patient who had a history of IDC was diagnosed with a recurrence of IDC with biopsy. The median SUVmax was 5.1 (range 1.5-9.4) for malignant breast lesions and 5.4 (range 2.2-12.6) for benign breast lesions., Conclusion: SSTR + breast lesions on DOTA PET are rarely seen in clinical practice. Uptakes of breast lesions in our cases were variable and not useful for differential diagnosis of lesions. It seems that SSTR + breast lesions should be evaluated with clinical and radiological characteristics, and correlative breast imaging and/or histopathological verification should be performed for suspicious lesions to avoid misdiagnosis.

Objection: We aimed to evaluate the role of bone scintigraphy (BS) which has long been the imaging modality of choice in prostate cancer (PCa) and performed a head-to-head comparison between BS, BS + SPECT/CT and 68 Ga-PSMA-PET/CT, for the detection of bone metastasis of PCa., Methods: We evaluated 138 PCa patients who underwent BS and 68 Ga-PSMA PET/CT and SPECT/CT of 102 of 138 patients. Images were interpreted retrospectively and areas of abnormally increased tracer uptake related to PCa were documented as benign, metastatic or equivocal. Equivocal uptakes were finally diagnosed based on a consensus review of correlative imaging. Patient- and lesion-based analysis was performed. Patients with superscan images were excluded from lesion-based analysis., Results: At least one metastatic or equivocal uptake in skeleton was defined in 76 of 138 (55%) BS, in 33 of 102 (32.3%) SPECT/CT, and in 49 of 138 (35.5%) 68 Ga-PSMA PET/CT. 23 (16.7%) patients had also superscan findings on BS and 68 Ga-PSMA PET/CT. For patient-based analysis, sensitivity, specificity, accuracy, PPV, and NPV were calculated as 91.1%, 64.5%, 73.1%, 55.4% and 93.7% for BS; 95.5%, 82.7%, 86.9%, 72.8% and 96.2% for BS + SPECT/CT; 97.7%, 95.7%, 95.6%, 91.6% and 98.8% for 68 Ga-PSMA PET/CT. For lesion-based analysis, sensitivity, specificity, accuracy, PPV, and NPV were 53%, 63.9%, 60.1%, 42.8% and 71.8% for BS; 59.2%, 87.6%, 77.7%, 62.6% and 80% for BS + SPECT/CT; 96.4%, 98.1%, 97.5%, 96.4% and 98.1% for 68 Ga-PSMA PET/CT., Conclusion: This study has shown that 68 Ga-PSMA PET/CT overcomes the limitations of BS and proves superiority in detecting bone metastases, even in patients with SPECT/CT. Our findings present important implications that 68 Ga-PSMA PET/CT can replace BS in future practice.

Objective: Minimizing side effects by using response-adopted therapy strategies plays an important role in the management of pediatric Hodgkin lymphoma (HL); however, the criteria for the definition of adequate or inadequate response are controversial. The aim of this study is to compare different methods of interpretation of 18 F-FDG-PET/CT (PET) in the prediction of disease outcome in order to determine the optimum method in this regard., Methods: Baseline, interim and post-treatment PET scans of 72 children were interpreted according to revised International Harmonization Project criteria (IHP) and Deauville criteria. Cut-off values for changes in interim and post-treatment FDG uptake (ΔSUV max ) in the prediction of progression-free survival (PFS) were measured using ROC analysis. Quantitative and visual data were compared with each other in the prediction of PFS., Results: Mean interim and post-treatment ΔSUV max of the primary lesions were 77.4 ± 19.5 and 68.8 ± 30.4% and respective cut-off values were 82 and 73%. However, only post-treatment ΔSUV max yielded statistically significant results in the prediction of 3-year PFS (p = 0.043). Interim ΔSUV max was further analyzed according to the values reported in the literature (66 and 77%) yet statistically significant results were not reached (p = 0.604 and 0.431). For interim evaluation, IHP criteria was correlated to Deauville criteria (p = 0.002 and p = 0.001) and ΔSUV max (p = 0.03), whereas for post-treatment evaluation, significant correlation with ΔSUV max (p = 0.04) but marginally significant (p = 0.055 and p = 0.058) correlation with Deauville criteria were achieved. Overall, 1, 3 and 5-year PFS were 95.7 ± 0.2, 89.6 ± 0.4 and 80.8 ± 0.7%, respectively. All methods demonstrated comparable performance in the prediction of 3-year PFS; however, interim PET using Deauville criteria and post-treatment PET using IHP criteria were statistically significant. All methods demonstrated high negative-predictive value but substantially low positive-predictive value., Conclusions: Deauville criteria are superior to other methods in the prediction of pediatric HL outcome using interim PET data. On the other hand, quantitative evaluation and visual evaluation by IHP can be used reliably at the end of the treatment. In this regard, we report the optimal cut-off value of SUV max reduction as 73%.

(18)F-NaF was used as a bone-seeking PET tracer for skeletal imaging until the introduction of the widely available (99m)Tc-labeled bone agents. However, there is renewed clinical interest in (18)F-NaF since prior technical and logistic limitations to its routine use are no longer present, and, as a consequence, it is likely that uptake unrelated to bone and non-osseous findings will be encountered more frequently. As a result of tumoral necrosis, soft tissue metastases may demonstrate (18)F-NaF avidity due to dystrophic calcification. On the other hand, all non-osseous findings, whether (18)F-NaF avid or not, may provide important diagnostic information that may alter the course of the disease, including treatment options. Herein we present a patient with ductal carcinoma of the breast in whom findings unrelated to the skeletal system in (18)F-NaF PET/CT altered the treatment strategy.

Alveolar hydatid disease or alveolar echinococcosis is a disease of the parasite Echinococcus multilocularis that is potentially fatal if left untreated. It primarily involves the liver but can be disseminated to other organs like the lungs and the brain by hematogenous route. Multiorgan involvement and the aggressive appearance of lesions make alveolar hydatid disease easy to confuse with a metastatic malignancy. For this reason, histopathological confirmation is essential for definite diagnosis. We present the imaging features of this disease in two patients in order to emphasize that these lesions can be easily misdiagnosed as malignancies.