Dosimetry and pharmacokinetics of [177Lu]Lu-satoreotide tetraxetan in patients with progressive neuroendocrine tumours.

PURPOSE: To evaluate the dosimetry and pharmacokinetics of the novel radiolabelled somatostatin receptor antagonist [177Lu]Lu-satoreotide tetraxetan in patients with advanced neuroendocrine tumours (NETs). METHODS: This study was part of a phase I/II trial of [177Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three planned cycles (median activity/cycle: 4.5 GBq), in 40 patients with progressive NETs. Organ absorbed doses were monitored at each cycle using patient-specific dosimetry; the cumulative absorbed-dose limits were set at 23.0 Gy for the kidneys and 1.5 Gy for bone marrow. Absorbed dose coefficients (ADCs) were calculated using both patient-specific and model-based dosimetry for some patients. RESULTS: In all evaluated organs, maximum [177Lu]Lu-satoreotide tetraxetan uptake was observed at the first imaging timepoint (4 h after injection), followed by an exponential decrease. Kidneys were the main route of elimination, with a cumulative excretion of 57-66% within 48 h following the first treatment cycle. At the first treatment cycle, [177Lu]Lu-satoreotide tetraxetan showed a median terminal blood half-life of 127 h and median ADCs of [177Lu]Lu-satoreotide tetraxetan were 5.0 Gy/GBq in tumours, 0.1 Gy/GBq in the bone marrow, 0.9 Gy/GBq in kidneys, 0.2 Gy/GBq in the liver and 0.8 Gy/GBq in the spleen. Using image-based dosimetry, the bone marrow and kidneys received median cumulative absorbed doses of 1.1 and 10.8 Gy, respectively, after three cycles. CONCLUSION: [177Lu]Lu-satoreotide tetraxetan showed a favourable dosimetry profile, with high and prolonged tumour uptake, supporting its acceptable safety profile and promising efficacy. TRIAL REGISTRATION: NCT02592707. Registered October 30, 2015.

A phase I/II study of the safety and efficacy of [177Lu]Lu-satoreotide tetraxetan in advanced somatostatin receptor-positive neuroendocrine tumours.

PURPOSE: We present the results of an open-label, phase I/II study evaluating the safety and efficacy of the novel somatostatin receptor (SSTR) antagonist [177Lu]Lu-satoreotide tetraxetan in 40 patients with previously treated, progressive neuroendocrine tumours (NETs), in which dosimetry was used to guide maximum administered activity. METHODS: This study was conducted in two parts. Part A consisted of 15 patients who completed three cycles of [177Lu]Lu-satoreotide tetraxetan at a fixed administered activity and peptide amount per cycle (4.5 GBq/300 µg). Part B, which included 25 patients who received one to five cycles of [177Lu]Lu-satoreotide tetraxetan, evaluated different administered activities (4.5 or 6.0 GBq/cycle) and peptide amounts (300, 700, or 1300 µg/cycle), limited to a cumulative absorbed radiation dose of 23 Gy to the kidneys and 1.5 Gy to the bone marrow. RESULTS: Median cumulative administered activity of [177Lu]Lu-satoreotide tetraxetan was 13.0 GBq over three cycles (13.1 GBq in part A and 12.9 GBq in part B). Overall, 17 (42.5%) patients experienced grade ≥ 3 treatment­related adverse events; the most common were lymphopenia, thrombocytopenia, and neutropenia. No grade 3/4 nephrotoxicity was observed. Two patients developed myeloid neoplasms considered treatment related by the investigator. Disease control rate for part A and part B was 94.7% (95% confidence interval [CI]: 82.3-99.4), and overall response rate was 21.1% (95% CI: 9.6-37.3). CONCLUSION: [177Lu]Lu-satoreotide tetraxetan, administered at a median cumulative activity of 13.0 GBq over three cycles, has an acceptable safety profile with a promising clinical response in patients with progressive, SSTR-positive NETs. A 5-year long-term follow-up study is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02592707. Registered October 30, 2015.

Radiation Dosimetry of Theragnostic Pairs for Isotopes of Iodine in IAZA.

Theragnostic pairs of isotopes are used to infer radiation dosimetry for a therapeutic radiopharmaceutical from a diagnostic imaging study with the same tracer molecule labelled with an isotope better suited for the imaging task. We describe the transfer of radiation dosimetry from the diagnostic radioiodine isotope 123I, labelled for the hypoxia tracer molecule iodoazomycin arabinoside ([123I]IAZA), to isotopes 131I (therapeutic) and 124I (PET imaging). Uncertainties introduced by the dissimilar isotope half-lives are discussed in detail. Radioisotope dosimetries for [123I]IAZA were obtained previously. These data are used here to calculate residence times for 131I and 124I and their uncertainties. We distinguish two cases when extrapolating to infinity: purely physical decay (case A) and physical decay plus biological washout (case B). Organ doses were calculated using the MIRD schema with the OLIDNA/EXM code. Significant increases in some organ doses (in mSv per injected activity) were found for 131I and 124I. The most affected organs were the intestinal walls, thyroid, and urinary bladder wall. Uncertainty remained similar to 123I for case A but considerably greater for case B, especially for long biological half-lives (GI tract). Normal tissue dosimetries for IAZA must be considered carefully when substituting isotope species. A long biological half-life can significantly increase dosimetric uncertainties. These findings are relevant when considering PET imaging studies with [124I]IAZA or therapeutic administration of [131I]IAZA.

A novel procedure to investigate social anxiety using videoconferencing software: A proof-of-concept study.

Social anxiety disorder (SAD) is very common and can be significantly disabling. New treatments are needed as the remission rate for SAD is the lowest of all the anxiety disorders. Experimental medicine models, in which features resembling a clinical disorder are experimentally induced, are a cost-effective and timely approach to explore potential novel treatments for psychiatric disorders. Following the emergence of SARS-CoV-2, there is a need to develop experimental medicine models that can be carried out remotely. We developed a novel procedure to investigate SAD (the InterneT-based Stress test for Social Anxiety Disorder; ITSSAD) that can be carried out entirely online by a single investigator, potentially reducing costs and maximising internal reliability. The procedure involves an anticipatory period followed by a naturalistic social interaction task. In a sample of 20 non-treatment-seeking volunteers with symptoms of SAD, the ITSSAD induced significant subjective anxiety and reduced positive affect. Further, increased social anxiety symptoms at baseline predicted increased anxiety during the social interaction task. This protocol needs further validation with physiological measures. The ITSSAD is a new tool for researchers to investigate mechanisms underlying social anxiety disorder.

Rapid Standardized CT-Based Method to Determine Lean Body Mass SUV for PET-A Significant Improvement Over Prediction Equations.

In 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) studies, maximum standardized uptake value (SUVmax) is the parameter commonly used to provide a measurement of the metabolic activity of a tumor. SUV normalized by body mass is affected by the proportions of body fat and lean tissue, which present high variability in patients with cancer. SUV corrected by lean body mass (LBM), denoted as SUL, is recommended to provide more accurate, consistent, and reproducible SUV results; however, LBM is frequently estimated rather than measured. Given the increasing importance of a quantitative PET parameter, especially when comparing PET studies over time to evaluate disease response clinically, and its use in oncological clinical trials, we set out to evaluate the commonly used equations originally derived by James (1976) and Janmahasatian et al. (2005) against computerized tomography (CT)-derived measures of LBM. Methods: Whole-body 18F-FDG PET images of 195 adult patients with cancer were analyzed retrospectively. Representative liver SUVmean was normalized by total body mass. SUL was calculated using a quantitative determination of LBM based on the CT component of the PET/CT study (LBMCT) and compared against the equation-estimated SUL. Bland and Altman plots were generated for SUV-SUL differences. Results: This consecutive sample of patients undergoing usual care (men, n = 96; women, n = 99) varied in body mass (38-127 kg) and in Body Mass Index (BMI) (14.7-47.2 kg/m2). LBMCT weakly correlated with body mass (men, r2 = 0.32; women, r2 = 0.22), and thus SUV and SULCT were also weakly correlated (men, r2 = 0.24; women, r2 = 0.11). Equations proved inadequate for the assessment of LBM. LBM estimated by James' equation showed a mean bias (overestimation of LBM compared with LBMCT) in men (+6.13 kg; 95% CI 4.61-7.65) and in women (+6.32 kg; 95% CI 5.26-7.39). Janmahasatian's equation provided similarly poor performance. Conclusions: CT-based LBM determinations incorporate the patient's current body composition at the time of a PET/CT study, and the information garnered can provide care teams with information with which to more accurately determine FDG uptake values, allowing comparability over multiple scans and treatment courses and will provide a robust basis for the use of PET Response Criteria in Solid Tumors (PERCIST) in clinical trials.

Tyrosine Kinase Inhibitors Reduce Glucose Uptake by Binding to an Exofacial Site on hGLUT-1: Influence on 18 F-FDG PET Uptake.

Positron emission tomography (PET) using 2-deoxy-2-[18 F]fluoro-d-glucose ([18 F]FDG), a marker of energy metabolism and cell proliferation, is routinely used in the clinic to assess patient response to chemotherapy and to monitor tumor growth. Treatment with some tyrosine kinase inhibitors (TKIs) causes changes in blood glucose levels in both nondiabetic and diabetic patients. We evaluated the interaction of several classes of TKIs with human glucose transporter-1 (hGLUT-1) in FaDu and GIST-1 cells by measuring [3 H]2-deoxy-d-glucose ([3 H]2-DG) and [3 H]FDG uptake. Uptake of both was inhibited to varying extents by the TKIs, and representative TKIs from each class showed competitive inhibition of [3 H]2-DG uptake. In GIST-1 cells, [3 H]FDG uptake inhibition by temsirolimus and nilotinib was irreversible, whereas inhibition by imatinib, gefitinib, and pazopanib was reversible. Molecular modeling studies showed that TKIs form multiple hydrogen bonds with polar residues of the sugar binding site (i.e., Q161, Q282, Q283, N288, N317, and W388), and van der Waals interactions with the H-pocket site. Our results showed interaction of TKIs with amino acid residues at the glucose binding site to inhibit glucose uptake by hGLUT-1. We hypothesize that inhibition of hGLUT-1 by TKIs could alter glucose levels in patients treated with TKIs, leading to hypoglycemia and fatigue, although further studies are required to evaluate roles of other SLC2 and SLC5 members. In addition, TKIs could affect tumor [18 F]FDG uptake, increasingly used as a marker of tumor response. The hGLUT-1 inhibition by TKIs may have implications for routine [18 F]FDG-PET monitoring of tumor response in patients.

Prolonged Response to Regorafenib in a Patient with Iodine Refractory Thyroid Cancer.

Thyroid cancer is the most common type of endocrine malignancy. Cornerstones of thyroid cancer treatment include surgery, radioactive iodine ablation, and thyroid stimulating hormone suppression. The National Comprehensive Cancer Network guidelines recommend two tyrosine kinase inhibitors for thyroid cancer patients who are non-responsive to iodine: sorafenib and lenvatinib. Another oral kinase inhibitor, regorafenib, is not considered standard of care treatment for differentiated thyroid cancer. The chemical structures of regorafenib and sorafenib differ by a single fluorine atom. Given the significant improvement in progression-free survival (PFS) of sorafenib compared to placebo demonstrated in the phase 3 DECISION trial, we report on a patient with iodine-refractory follicular thyroid cancer treated with regorafenib as part of a phase 1 clinical trial. A 75 year old woman was diagnosed with follicular thyroid carcinoma in 2006 and initiated on treatment with regorafenib in 2011. She has completed 76 cycles with stable disease and pulmonary metastases 34% smaller than baseline.

Efficacy of 177Lu Peptide Receptor Radionuclide Therapy for the Treatment of Neuroendocrine Tumors: A Meta-analysis.

OBJECTIVE: The purpose of this study was to assess the efficacy of Lu-labeled peptide receptor radionuclide therapy (PRRT) induction treatments for patients with unresectable metastatic neuroendocrine tumors. METHODS: MEDLINE, EMBASE, and Ovid were systematically searched with keywords "lutetium," "Lu-177," "PRRT," "neuroendocrine," and "prognosis." Studies evaluating treatment with Lu-labeled PRRT were assessed for disease response and/or disease control rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 or 1.1, modified RECIST, Southwest Oncology Group (SWOG), or modified SWOG criteria. Pooled proportions of disease response and control rates were calculated for both fixed- and random-effects models. RESULTS: Eighteen studies with 1920 patients were included (11 with 1268 patients using RECIST and 6 with 804 patients using SWOG). By RECIST criteria, the pooled disease response rate by random-effects model was 29.1% (95% confidence interval [CI], 20.2%-38.9%), and disease control rate was 74.1% (95% CI, 67.8%-80.0%). By SWOG criteria, the pooled disease response rate by random-effects model was 30.6% (95% CI, 20.7%-41.5%), and disease control rate was 81.1% (95% CI, 76.4%-85.4%). CONCLUSIONS: Induction therapy, typically 4 treatments, with Lu PRRT is an effective method of treating unresectable metastatic neuroendocrine tumors with significant disease response and control rates.

Follow-up Recommendations for Completely Resected Gastroenteropancreatic Neuroendocrine Tumors.

There is no consensus on optimal follow-up for completely resected gastroenteropancreatic neuroendocrine tumors. Published guidelines for follow-up are complex and emphasize closer surveillance in the first 3 years after resection. Neuroendocrine tumors have a different pattern and timescale of recurrence, and thus require more practical and tailored follow-up. The Commonwealth Neuroendocrine Tumour Collaboration convened an international multidisciplinary expert panel, in collaboration with the North American Neuroendocrine Tumor Society, to create patient-centered follow-up recommendations for completely resected gastroenteropancreatic neuroendocrine tumors. This panel used the RAND/UCLA (University of California, Los Angeles) Appropriateness Method to generate recommendations. A large international survey was conducted outlining current the surveillance practice of neuroendocrine tumor practitioners and shortcomings of the current guidelines. A systematic review of available data to date was supplemented by recurrence data from 2 large patient series. The resultant guidelines suggest follow-up for at least 10 years for fully resected small-bowel and pancreatic neuroendocrine tumors and also identify clinical situations in which no follow-up is required. These recommendations stratify follow-up strategies based on evidence-based prognostic factors that allow for a more individualized patient-centered approach to this complex and heterogeneous malignant neoplasm.

Pharmacokinetics and Scintigraphic Imaging of the Hypoxia-Imaging Agent [123I]IAZA in Healthy Adults Following Exercise-Based Cardiac Stress †.

The objective of this work is to evaluate the potential effect of cardiac stress exercise on the accumulation of [123I]IAZA, a radiopharmaceutical used to image focal tissue hypoxia, in otherwise normal myocardium in healthy volunteers, and to determine the impact of exercise on [123I]IAZA pharmacokinetics. The underlying goal is to establish a rational basis and a baseline for studies of focal myocardial hypoxia in cardiac patients using [123I]IAZA. Three healthy male volunteers ran the 'Bruce' treadmill protocol, a clinically-accepted protocol designed to expose myocardial ischemia in patients. The 'Bruce' criterion heart rate is 85% of [220-age]. Approximately one minute before reaching this level, [123I]IAZA (5.0 mCi/0.85 mg) was administered as a slow (1-3 min) single intravenous (i.v.) injection via an indwelling venous catheter. The volunteer continued running for an additional 1 min before being transferred to a gamma camera. Serum samples were collected from the arm contralateral to the administration site at pre-determined intervals from 1 min to 45 h post injection and were analyzed by radio HPLC. Pharmacokinetic (PK) parameters were derived for [123I]IAZA and total radioactivity (total[123I]) using compartmental and noncompartmental analyses. Whole-body planar scintigraphic images were acquired from 0.75 to 24 h after dosing. PK data and scintigraphic images were compared to previously published [123I]IAZA data from healthy volunteers rest. Following exercise stress, both [123I]IAZA and total[123I] exhibited bi-exponential decline profiles, with rapid distribution phases [half-lives (t1/2α) of 1.2 and 1.4 min, respectively], followed by slower elimination phases [t1/2ß of 195 and 290 min, respectively]. Total body clearance (CLTB) and the steady state volume of distribution (Vss) were 0.647 L/kg and 185 mL/min, respectively, for [123I]IAZA and 0.785 L/kg and 135 mL/min, respectively, for total[123I]. The t1/2ß, CLTB and Vss values were comparable to those reported previously for rested volunteers. The t1/2α was approximately 4-fold shorter for [123I]IAZA and approximately 3-fold shorter for total[123I] under exercise relative to rested subjects. The heart region was visualized in early whole body scintigraphic images, but later images showed no accumulated radioactivity in this region, and no differences from images reported for rested volunteers were apparent. Minimal uptake of radiotracer in myocardium and skeletal muscle was consistent with uptake in non-stressed myocardium. Whole-body scintigrams for [123I]IAZA in exercise-stressed healthy volunteers were indistinguishable from images of non-exercised volunteers. There was no evidence of hypoxia-dependent binding in exercised but otherwise healthy myocardium, supporting the conclusion that exercise stress at Bruce protocol intensity does not induce measurable myocardial hypoxia. Effects of exercise on PK parameters were minimal; specifically, the t1/2α was shortened, reflecting increased cardiac output associated with exercise. It is concluded that because [123I]IAZA was not metabolically bound in exercise-stressed myocardium, a stress test will not create elevated myocardial background that would mask regions of myocardial perfusion deficiency. [123I]IAZA would therefore be suitable for the detection of viable, hypoxic myocardium in patients undergoing stress-test-based diagnosis.

Comparison of 30 mCi and 50 mCi I-131 doses for ablation of thyroid remnant in papillary thyroid cancer patients.

PURPOSE OF THE STUDY: To compare efficacy of thyroid remnant ablation using 30 mCi or 50 mCi 131-I in papillary thyroid cancer patients. MATERIALS AND METHODS: Five hundred and fifteen consecutive patients with Tumor-Node-Metastasis (TNM) stages T1-T3 N1/N0/NX receiving either 30 mCi or 50 mCi I-131 were analyzed for the effectiveness of remnant ablation using rhTSH-stimulated serum thyroglobulin. One hundred and five consecutive patients receiving 100 mCi I-131 were analyzed for the incidence of radiation thyroiditis and sialadenitis. RESULTS AND CONCLUSIONS: Doses of 30 mCi and 50 mCi were equally effective for low- and moderate-risk disease but 30 mCi was less effective for T1T2NX disease, and 50 mCi was less effective for T3 compared to T1T2 disease. Low dose radiation hypersensitivity or unknown more extensive disease may have accounted for observed differences. Radiation thyroiditis and sialadenitis were more common in a comparison series of 100 mCi dose compared to 30 mCi, but not more common than in 50 mCi doses.

A population-based study of outcomes in patients with gastrointestinal neuroendocrine tumours.

BACKGROUND: Neuroendocrine tumours (NETs) are heterogeneous, with varying presentations and treatment options. To our knowledge, there are no randomized and few long-term studies of patient outcomes. The role of surgical and medical therapy for local, regional and metastatic disease continues to be evaluated in the literature. METHODS: We conducted a population-based search of the provincial cancer registry to identify patients with gastrointestinal NETs from the stomach, small intestine, colon and rectum diagnosed between 1990 and 2005 and assessed their outcomes. RESULTS: We examined clinicopathological information on the outcomes of 530 patients with gastrointestinal NETs. The overall incidence of NETs increased from 11 per million to 19 per million during the study period. Advancing stage and patient age were associated with poor overall or disease-specific outcomes. Surgery, both curative and palliative, was associated with decreased risk of overall (hazard ratio [HR] 0.5, p < 0.001) and disease-specific (HR 0.5, p < 0.001) death. The biggest benefit was observed in patients with distant disease, in whom 5-year disease-specific survival for R0 resections was nearly double that for patients with macroscopic residual disease (92% v. 48%, p = 0.009). Older age was associated with poor 5-year overall and disease-specific survival (p < 0.001). CONCLUSION: There has been a significant increase in incidence of gastrointestinal NETs, and advancing patient age, but not sex, is linked to poor outcomes in terms of overall and disease-specific survival. Surgery, both curative and palliative, was associated with decreased risk of overall and disease-specific death. Compared with patients with residual macroscopic disease, patients with distant disease were nearly twice as likely to survive 5 years if they had R0 resections. The use of radioisotope therapy and long-acting octreotide therapy was also associated with improved outcomes overall.

CONTEXTE: Les tumeurs neuroendocrines (TNE) sont hétérogènes, et les tableaux et options thérapeutiques sont variables. À notre connaissance, il n'existe pas d'études randomisées et il y a peu d'études à long terme sur les résultats chez les patients. Le rôle du traitement chirurgical et médicamenteux de la maladie locale, régionale et métastatique continue d'être évalué dans la littérature. MÉTHODES: Nous avons procédé à une interrogation démographique du Registre provincial du cancer pour recenser les patients atteints de TNE gastro-intestinales provenant de l'estomac, de l'intestin grêle, du côlon et du rectum, diagnostiqués entre 1990 et 2005 et nous avons évalué les résultats. RÉSULTATS: Nous avons examiné les données clinico-pathologiques des résultats enregistrés chez 530 patients atteints de TNE gastro-intestinales. L'incidence globale des TNE a augmenté de 11 par million à 19 par million pendant la période de l'étude. Le stade de la maladie et l'âge avancés ont été associés à des résultats globaux ou spécifiques à la maladie moins favorables. La chirurgie, curative et palliative, a été associée à un risque moindre de décès global (risque relatif [RR] 0.5, p < 0,001) et spécifique à la maladie (RR 0,5, p < 0,001). L'avantage le plus marqué a été observé chez les patients présentant une maladie distale, chez qui la survie à 5 ans spécifique à la maladie pour les résections R0 était près de 2 fois celle des patients présentant une maladie macroscopique résiduelle (92 % c. 48 %, p = 0,009). L'âge avancé a été associé à une survie à 5 ans globale et spécifique à la maladie défavorable (p < 0,001). CONCLUSION: L'incidence des TNE gastro-intestinales a significativement augmenté, et l'âge avancé des patients, mais non le sexe, est lié à des résultats défavorables aux plans de la survie globale et spécifique à la maladie. La chirurgie, curative et palliative, a été associée à un risque moindre de décès global et spécifique à la maladie. Comparativement aux patients ayant une maladie macroscopique résiduelle, ceux qui avaient une maladie distale étaient près de 2 fois plus susceptibles de survivre 5 ans s'ils avaient des résections R0. Les traitements par radio-isotopes et octréotide à longue durée d'action ont aussi été associés à une amélioration globale des résultats.

131I-MIBG Therapy in a Metastatic Small Bowel Neuroendocrine Tumor Patient Undergoing Hemodialysis.

Systemic radioisotope therapy with I-metaiodobenzylguanidine (I-MIBG) is an effective form of targeted therapy for neuroendocrine tumors. One of the absolute contraindications to administering I-MIBG therapy listed in the 2008 European Association of Nuclear Medicine guidelines is renal insufficiency requiring dialysis, although this contraindication is not evidence based. We describe a 68-year-old woman with a metastatic small bowel neuroendocrine tumor who developed renal insufficiency requiring hemodialysis. Imaging and dosimetry with I-MIBG were performed and showed that the radiation doses to the whole body and lungs were within safe limits. She was treated with 1820 MBq of I-MIBG with no short-term adverse reactions.

Clinical Trial with Sodium 99mTc-Pertechnetate Produced by a Medium-Energy Cyclotron: Biodistribution and Safety Assessment in Patients with Abnormal Thyroid Function.

A single-site prospective open-label clinical study with cyclotron-produced sodium 99mTc-pertechnetate (99mTc-NaTcO4) was performed in patients with indications for a thyroid scan to demonstrate the clinical safety and diagnostic efficacy of the drug and to confirm its equivalence with conventional 99mTc-NaTcO4 eluted from a generator. Methods:99mTc-NaTcO4 was produced from enriched 100Mo (99.815%) with a cyclotron (24 MeV; 2 h of irradiation) or supplied by a commercial manufacturer (bulk vial eluted from a generator). Eleven patients received 325 ± 29 (mean ± SD) MBq of the cyclotron-produced 99mTc-NaTcO4, whereas the age- and sex-matched controls received a comparable amount of the generator-derived tracer. Whole-body and thyroid planar images were obtained for each participant. In addition to the standard-energy window (140.5 keV ± 7.5%), data were acquired in lower-energy (117 keV ± 10%) and higher-energy (170 keV ± 10%) windows. Vital signs and hematologic and biochemical parameters were monitored before and after tracer administration. Results: Cyclotron-produced 99mTc-NaTcO4 showed organ and whole-body distributions identical to those of conventional 99mTc-NaTcO4 and was well tolerated. All images led to a clear final diagnosis. The fact that the number of counts in the higher-energy window was significantly higher for cyclotron-produced 99mTc-NaTcO4 did not influence image quality in the standard-energy window. Image definition in the standard-energy window with cyclotron-produced 99mTc was equivalent to that with generator-eluted 99mTc and had no particular features allowing discrimination between the 99mTc production methods. Conclusion: The systemic distribution, clinical safety, and imaging efficacy of cyclotron-produced 99mTc-NaTcO4 in humans provide supporting evidence for the use of this tracer as an equivalent for generator-eluted 99mTc-NaTcO4 in routine clinical practice.

Metastatic Insulinoma Pancreatic Neuroendocrine Tumor Treated With 177Lu-DOTATATE Induction and Maintenance Peptide Receptor Radionuclide Therapy: A Suggested Protocol.

A 70-year-old woman presented with frequent episodes of hypoglycemia. Imaging revealed a 6-cm pancreatic mass with several liver lesions. The pancreatic mass was resected and confirmed to be a well-differentiated insulinoma. Surgery improved but did not resolve her hypoglycemic episodes, and she was referred for peptide receptor radionuclide therapy with 177Lu-DOTATATE to treat her residual disease. A modified protocol with a continuous IV dextrose infusion was used, and the treatments were well tolerated. After 4 induction and 2 maintenance treatments, her hypoglycemic symptoms resolved completely and her disease stabilized. She has been progression free for 24 months.

Chest X-ray Artifact Caused by Bilateral 99mTc-Antimony Trisulfite Injection for Sentinel Node Imaging in a Patient With Breast Cancer.

A 52-year-old woman diagnosed with invasive ductal carcinoma of both breasts had a chest x-ray for preoperative assessment. A striking artifact was noted by the x-ray technologist, who, as a result, became very concerned about radiation exposure from the patient. The patient had undergone bilateral sentinel lymph node injections in the nuclear medicine department with Tc-antimony trisulfite colloid just 2 hours before the chest x-ray. Radiation exposure to the x-ray technologist was determined to be similar to 8 hours of naturally occurring background radiation (∼2.96 µSv).

Palliation of Extensive Metastatic Bone Disease With 223Ra-Dichloride α-Particle Therapy in a Patient With Malignant Hereditary Paraganglioma-Pheochromocytoma Syndrome With SDHB Mutation.

A 26-year-old woman with a 5-year history of metastatic paraganglioma due to hereditary paraganglioma-pheochromocytoma syndrome with SDHB mutation, who had failed multiple treatment regimens and had transfusion dependent pancytopenia, presented with progressive liver and bone metastases. She was unable to sleep due to painful skull metastases and had severe weakness in her extremities that limited her mobility and daily activities. She was treated with 2 doses of Ra-dichloride (Xofigo, Ra) and had a dramatic improvement in pain control, mobility, and overall quality of life for 8 weeks, before passing away from pulmonary hemorrhage.

Combined Treatment With 131I-MIBG and Sunitinib Induces Remission in a Patient With Metastatic Paraganglioma Due to Hereditary Paraganglioma-Pheochromocytoma Syndrome From an SDHB Mutation.

A 22-year-old woman with rapidly progressing metastatic paraganglioma due to hereditary paraganglioma-pheochromocytoma syndrome from an SDHB mutation, who recurred after neoadjuvant chemotherapy, was found to be MIBG avid. She was treated with 2 I-MIBG treatments and concurrent sunitinib, achieving a complete response. She was in full remission for 9 months before developing bone metastases.

Ectopic Corticotropin-Producing Neuroendocrine Tumor of the Pancreas Treated With 177Lu DOTATATE Induction and Maintenance Peptide Receptor Radionuclide Therapy.

A 57-year-old woman diagnosed with ectopic Cushing syndrome was found to have a 111In-octreotide-avid corticotropin-producing pancreatic neuroendocrine tumor with liver metastases. She was treated with 4 induction and 4 maintenance cycles of 177Lu-DOTATATE, which normalized her serum corticotropin levels and dramatically reduced the size of the pancreatic primary and liver metastases.

Orbital Metastases of Neuroendocrine Tumors Treated With 177Lu-DOTATATE PRRT or 131I-MIBG Therapies.

Neuroendocrine tumors have a propensity to metastasize to the orbit, although the reason is unknown. A review of 251 neuroendocrine tumors treated with Lu-DOTATATE or I-MIBG at our institution since 2003 revealed 4 patients with orbital metastases (1.6%), 2 treated with Lu-DOTATATE and 2 with I-MIBG. Of these 4 patients, 1 patient was symptomatic with diplopia and eye pain, and 2 patients had physical signs of orbital involvement. The symptomatic orbital metastasis improved with Lu-DOTATATE therapy, and proptosis improved with I-MIBG therapy in 1 of 2 patients. We present the imaging findings of these 4 patients, as well as their management.