Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Adults with Inoperable or Metastatic Somatostatin Receptor-Positive Pheochromocytomas/Paragangliomas, Bronchial and Unknown Origin Neuroendocrine Tumors, and Medullary Thyroid Carcinoma: A Systematic Literature Review.

BACKGROUND: We have performed a systematic review to evaluate the efficacy and safety of [177Lu]Lu-DOTA-TATE, a radioligand therapy, in advanced somatostatin receptor-positive pheochromocytoma/paraganglioma (PPGL), thymic neuroendocrine tumor (NET), bronchial NET, unknown primary NET, or medullary thyroid carcinoma (MTC). METHODS: Studies identified in PubMed from inception to 13 May 2021 must have assessed [177Lu]Lu-DOTA-TATE as a single agent and reported outcome data for the specific NET types of interest. RESULTS: Two independent reviewers performed the screening and data extraction, resulting in 16 publications: PPGL (n = 7), bronchial NETs (n = 6; one also included NETs of unknown origin), and MTC (n = 3). Overall, [177Lu]Lu-DOTA-TATE offers encouraging antitumor activity (overall tumor response rates and disease control rates) across NET types. Safety was favorable with most adverse events mild to moderate in severity, transient, and consistent with those seen in patients with gastroenteropancreatic (GEP)-NETs. CONCLUSIONS: [177Lu]Lu-DOTA-TATE has been used effectively in clinical practice to treat NETs of non-GEP origin.

Articular 18Fluorodeoxyglucose Uptake Is Associated With Clinically Assessed Swollen Joint Count in Patients With Rheumatoid Arthritis.

OBJECTIVE: Examination and conventional radiography of joints are unable to precisely evaluate and measure disease activity in rheumatoid arthritis (RA). We quantified joint inflammation using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in people with RA to determine if PET-derived uptake variables were correlated with RA disease activity measures. METHODS: We cross-sectionally studied 34 patients with RA in a substudy of the Rheumatoid Arthritis Study of the Myocardium (RHYTHM). All patients underwent 18F-FDG-PET scanning with CT for attenuation correction and anatomic co-registration. Linear regression was used to model the associations of disease activity scores with articular FDG uptake, calculated as standardized uptake values (SUVs). Weighted joint volume SUVs (wjSUV) representing 25%, 50%, 75%, and maximum (100%) uptake (wj25SUV, wj50SUV, wj75SUV, and wjMaxSUV, respectively) were calculated as global variables of the total volume of joint inflammation in each patient. RESULTS: Calculated wj25SUV (Spearman ρ = 0.39, P = 0.04), wj50SUV (ρ = 0.39, P = 0.04), and wj75SUV (ρ = 0.37, P = 0.045) measures were significantly correlated with the number of swollen joints. Similar significant correlations were found for the Simplified Disease Activity Index but not Clinical Disease Activity or Disease Activity Score in 28 joints. No associations were found between articular FDG uptake and nonarticular RA-related variables (ie, disease duration, seropositivity, or RA treatments). CONCLUSION: Articular FDG uptake in patients with RA was significantly correlated with the number of swollen joints but not with biochemical measures of inflammation.

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study.

PURPOSE: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. METHODS: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. RESULTS: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. CONCLUSIONS: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov : NCT01578239, EudraCT: 2011-005049-11.

Comparison of Bone Uptake in Bone Scan and Ga-68 PSMA PET/CT Images in Patients with Prostate Cancer.

OBJECTIVE: The aim of this study was to compare images from Tc-99m MDP bone scan (BS) and Ga-68 PSMA PET/CT of patients with prostate cancer in terms of bone metastases. METHODS: Overall, 34 patients exhibited a mean age of 66 ± 9.5 (50-88) years, mean PSA of 51 ± 159ng/ml (0-912), and mean Gleason score of 8 (6-9). BS and Ga-68 PSMA PET/CT were applied to 34 patients within 30 days, and the results were evaluated, retrospectively. In both tests, radiopharmaceutical uptake in bones were compared. RESULTS: In 7 patients (20.5%), uptake was not significant on BS and Ga-68 PSMA PET / CT images, which is related to metastasis. In 14 (41%) patients, bone metastases were observed in both examinations. However, more metastatic lesions were observed in the Ga-68 PSMA PET/CT of 3 patients and in the bone scintigraphy of 2 patients. PSMA expression was not observed on Ga-68 PSMA PET / CT in 13 (38%) patients with increased activity in bone scintigraphy. Two (6%) of these patients were thought to be metastatic, 2 (6%) were suspicious for metastasis, and 9 (26%) had no metastasis. When a lesion-based evaluation was performed, a total of 480 activities were evaluated: increased activity uptake was found in 305 BS, and 427 PSMA expression activity was detected. Furthermore, 435 of these activities were evaluated as metastatic. CONCLUSION: Ga-68 PSMA PET/CT provides an additional contribution to the BS evaluation of activity areas because of the presence of PSMA expression and anatomical lesions. In 6% of the patients, activity on BS and metastatic appearance in CT images were observed and the presence of lesions in the absence of PSMA was determined. This suggests that bone metastases without PSMA expression may also be present.

Nuclear Molecular and Theranostic Imaging for Differentiated Thyroid Cancer.

Traditional nuclear medicine is rapidly being transformed by the evolving concepts in molecular imaging and theranostics. The utility of new approaches in differentiated thyroid cancer (DTC) diagnostics and therapy has not been fully appreciated. The clinical information, relevant to disease management and patient care, obtained by scintigraphy is still being underestimated. There has been a trend towards moving away from the use of radioactive iodine (RAI) imaging in the management of the disease. This paradigm shift is supported by the 2015 American Thyroid Association Guidelines (1). A more systematic and comprehensive understanding of disease pathophysiology and imaging methodologies is needed for optimal utilization of different imaging modalities in the management of DTC. There have been significant developments in radiotracer and imaging technology, clinically proven to contribute to the understanding of tumor biology and the clinical assessment of patients with DTC. The research and development in the field continues to evolve, with expected emergence of many novel diagnostic and therapeutic techniques. The role for nuclear imaging applications will continue to evolve and be reconfigured in the changing paradigm. This article aims to review the clinical uses and controversies surrounding the use of scintigraphy, and the information it can provide in assisting in the management and treatment of DTC.

Dual-phase F-18 FDG PET-CT in staging and lymphoscintigraphy for detection of sentinel lymph nodes in oral cavity cancers.

AIM: Our objective was to evaluate the diagnostic role of dual-phase fluor-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography-computed tomography (PET-CT) and planar lymphoscintigraphy in patients with oral cavity cancer (OCC). We also investigated the combined impact of F-18 FDG PET-CT and sentinel lymph node biopsy (SLNB) in decision making for patients with OCC. METHODS: Sixteen patients (4 female, 12 male; age range, 29-81 years) were included in this prospective study. F-18 FDG PET-CT [1 (early) and 2 h (delayed) after injection] and planar lymphoscintigraphy (2h before the surgery) were performed for all the patients before surgery. The sensitivity, specificity, and negative and positive predictive values in F-18 FDG PET-CT for the early and the delayed scans and tumor/liver uptake (T/L) in the lymph nodes were calculated. Receiver operating characteristic curves were obtained for standardized uptake value (SUV)max and T/L. RESULTS: Histopathological evaluations revealed that 5 patients had metastatic lymph nodes (pN+) whereas 11 patients had benign lymph nodes (pN-). Out of 43 lymph nodes visualized as cN(+) in F-18 FDG PET-CT, 14 were pathologically positive for malignancy, whereas 29 were pathologically benign. There was no statistical difference between the N(+) and N(-) patients in terms of age, depth of primary tumor, and the number of mitoses. However, there was a significant difference between the N(+) and N(-) patients (P=.011) in terms of early and delayed F-18 FDG uptake of primary tumors. There was a statistically significant difference in the value of SUVmax between the early and the delayed scans for the malignant lymph nodes (P=.00). CONCLUSION: This study indicates that F-18 FDG PET-CT is a reliable method for the correct evaluation of primary tumor and N staging in OCCs. Delayed phase of F-18 FDG imaging may increase primary lesion detectability due to higher FDG uptake in primary tumors compared to the early phase of imaging. F-18 FDG PET-CT might demonstrate skip metastasis in lymph nodes which can be missed with SLNB. Although SUV values increased in the delayed phase of F-18 PET-CT imaging in detecting lymph node metastases, the specificity and positive predictive value did not increase.

The diagnostic role of dual-phase (18)F-FDG PET/CT in the characterization of solitary pulmonary nodules.

OBJECTIVE: Our objective was to evaluate the diagnostic role of dual-phase (18)F-fluorodeoxyglucose ((18)F-FDG) PET/computed tomography (CT) in the characterization of solitary pulmonary nodules (SPNs). PATIENTS AND METHODS: A total of 48 SPNs in 48 patients were included in this retrospective study. The final diagnosis was confirmed histopathologically or by follow-up CT. Two PET/CT scans were performed: the first (early scan) was performed 1 h after injection and the second (delayed scan) was performed 2 h later. Standardized uptake values (SUVs) [early and delayed SUVmax and SUVmean adjusted to body weight, body surface area (BSA), lean body mass (LBM) and blood glucose level (Glc)], retention index and nodule-to-mediastinum (nodule activity/subcarinal region of interest activity) ratios were calculated, along with the receiver operating characteristic curve. Intraobserver and interobserver variabilities among nuclear medicine physicians were analysed for the two phases. RESULTS: Eighteen patients had malignant tumour, whereas 30 had benign lesions. The median (min-max) SUVmax was 1.5 (0.5-4.1) in the benign group and 3.6 (1.3-38) in the malignant group. With the threshold value of early SUVmax as 2.5 and 2.75 using the receiver operating characteristic curve, a sensitivity of 94-75%, specificity of 75-80% and an accuracy of 83-78% were calculated. With the same threshold values for delayed images, 94-100% sensitivity, 77-80% specificity and 83-88% accuracy were obtained. BSA-SUVmax, LBM-SUVmax and Glc-SUVmax did not show any advantage over other quantitative parameters in the SPN characterization. There was no variability in the results obtained between the two nuclear medicine physicians. CONCLUSION: Dual-phase PET/CT may increase the diagnostic potential of PET/CT in the characterization of SPNs. In this particular study group, a threshold value could not be determined for the retention index, but higher retention indices may show higher malignant potential in SPNs.