Global challenges in access to diagnostics and treatment for neuroendocrine tumor (NET) patients.

SCAN, an online survey, measured access to diagnosis, treatments and monitoring of neuroendocrine tumor (NET) patients globally. Between September and November 2019, NET patients and healthcare professionals (HCPs) completed an online, semi-standardized survey with 54 patient questions and 33 HCP questions. A total of 2359 patients with NETs and 436 HCPs responded. Misdiagnosis was common (44% [1043/2359]). Mean time to diagnosis was 4.8 years (standard deviation [SD], 6.2). Compared with global figures (60% [1407/2359]), the availability of 68 Ga-DOTA positron emission tomography (PET)/computed tomography (CT) was significantly lower in Asia (45% [126/280]) and higher in Oceania (86% [171/200]). HCPs reported that 68 Ga-DOTA PET/CT was free/affordable to fewer patients in Emerging and Developing Economies (EDE) than Advanced Economies (AE; 17% [26/150] and 59% [84/142], respectively). Compared with global data (52% [1234/2359]), patient-reported availability of peptide receptor radionuclide therapy (PRRT) was significantly lower in Asia (31% [88/280]) and higher in Oceania (61% [122/200]). Significant differences were observed in average annual NET specialist costs between AE and EDE ($1081 and $2915, respectively). Compared with AE, patients in EDE traveled further for NET specialists (1032 [SD, 1578] and 181 [SD, 496] km, respectively). Patients and HCPs both recommended referral to HCPs that were more knowledgeable in the field of NETs and had better access to NET experts/specialist centers. National care pathways, enhancing HCP NET knowledge and ensuring effective diagnostics and access to appropriate treatments are crucial to improving patient survival and NET care worldwide.

Unmet needs in the international neuroendocrine tumor (NET) community: Assessment of major gaps from the perspective of patients, patient advocates and NET health care professionals.

Due to the increasing incidence and prevalence of neuroendocrine tumors (NETs), there is a need to assess any gaps in awareness and care. A survey was undertaken in 2017 to identify perceived unmet needs from the perspectives of patients/families, patient advocates and health care professionals (HCPs). The survey consisted of 33-37 questions (depending on type of respondent) across four areas: information, care, treatments and research. In total, 443 participants from 26 countries responded: 338 patients/families, 35 advocates and 70 HCPs. Perceived unmet needs regarding provision of information at diagnosis differed between groups. While 59% of HCPs believed they provided sufficient information, informational needs were mostly/fully met for only 30% of patients and 18% of advocates. Additionally, 91% of patients and 97% of advocates felt that patients had to search for information themselves. Availability of Gallium-68-Dotatate PET/CT scan was limited for the majority of patients (patients: 73%; advocates: 85%; HCP: 86%), as was access to treatments, particularly peptide receptor radionuclide therapy (patients: 42%; advocates: 95%; HCPs: 77%). All groups felt that standards of care, including psychological needs and diagnosis of mental health, were not fully met. Although about two-thirds of patients were managed by a multidisciplinary team, 14% of patients reportedly did not have enough contact. All groups supported more patient involvement in research; patients and advocates prioritized improvement in diagnosis and HCPs focused on clinical trials. This survey revealed significant unmet needs but differing perceptions regarding these among the groups. There is a need for investigation and collaboration to improve standards of care for NET patients.

Radiation Exposure to the Nuclear Medicine Personnel During Preparation and Handling of 213Bi-Radiopharmaceuticals.

Because of the excellent ability of α-particles to transfer a high amount of energy over a short tissue range, targeted α-therapy has been attracting rising numbers of nuclear medicine centers. In this study, we estimated the radiation exposure to the occupational workers with pocket dosimeters during handling of the α-emitter 213Bi, used for targeted α-therapy of neuroendocrine tumor and castration-resistant prostate cancer patients. The dose rates from patients at different distances and time points after injection of the therapy were also evaluated. Methods: This prospective study was done in the Department of Nuclear Medicine at Fortis Memorial Research Institute, Gurgaon, India. Twelve patients with neuroendocrine tumors or castration-resistant prostate cancer were enrolled to receive 213Bi-DOTATOC or 213Bi-prostate-specific membrane antigen therapy, respectively. Each patient received 2-3 intravenous injections of 213Bi-peptide, 266-362 MBq (7.2-9.8 mCi) in a single cycle over 2-3 d. The radiation exposure to nuclear medicine personnel at the chest and extremity levels was assessed for tasks such as elution, dispensing, injecting, and collecting blood samples. Radiation levels were measured at distances of 1 cm and 1 m from patients immediately after, and at 1, 2, and 4 h after, the administration of 213Bi-peptide. Results: The external dose incurred at the chest level by radiopharmacists during synthesis, by physicians during injection, by technologists during imaging, and by nurses during sample collection was 2-7 µSv/procedure. The extremity dose was 1-14 µSv/procedure. The dose rate at 1 m from patients immediately after 213Bi-radiopharmaceutical injection was 0.02-0.03 µSv/MBq⋅h. Conclusion: The external radiation doses received by occupational workers involved in various procedures were far below the limit prescribed by the regulatory authority (20 mSv/y).

Molecular Imaging to the Surgeons Rescue: Gallium-68 DOTA-Exendin-4 Positron Emission Tomography-Computed Tomography in Pre-operative Localization of Insulinomas.

BACKGROUND: Insulinoma is an islet-cell neoplasm that secretes insulin. It is usually localized to the pancreas and is often the most common cause of endogenous hyperinsulinemic hypoglycaemia in non-diabetic adult patients. Surgical excision with a curative intent is the standard modality of treatment, and it requires precise localization of tumor tissue. Ga-68 DOTA-exendin-4 PET/CT scan is a clinically reasonable and sensitive scan for the identification of insulinoma. The aim of this prospective cohort study was to determine the overall accuracy of Ga-68 DOTA-exendin-4 PET/CT scan in the detection of insulinoma. MATERIALS AND METHODS: Eight patients with fasting hyperinsulinemic hypoglycaemia with neuroglycopenic symptoms were enrolled in this study which was conducted during October 2016 to October 2017. Whole body PET/CT scan was performed on a Philips time of flight PET/CT scanner, 60 minutes after injection of Ga-68 DOTA-exendin-4 (and also Ga-68 DOTANOC). The imaging findings were compared to the histopathological diagnosis in six out of eight patients and to subsequent follow up in the remaining two patients who did not undergo surgery. RESULTS: The sensitivity of Ga-68 DOTA-Exendin-4 PET/CT scan in insulinoma detection was found to be 75%. CONCLUSION: Ga-68 DOTA-Exendin-4 PET/CT scan is highly sensitive for identification and exact localization of insulinoma which can guide better surgical exploration. However, randomised controlled trials are needed to assess the accuracy of Ga-68 DOTA-Exendin PET/CT scan in localization of insulinoma.

Dosimetric analysis of patients with gastro entero pancreatic neuroendocrine tumors (NETs) treated with PRCRT (peptide receptor chemo radionuclide therapy) using Lu-177 DOTATATE and capecitabine/temozolomide (CAP/TEM).

OBJECTIVE:: Two radiosensitizing chemotherapeutic drugs, capecitabine (CAP) and temozolomide (TEM), are administered concurrently to enhance the therapeutic efficacy of peptide receptor radionuclide therapy (PRRT). This study aims to assess the biodistribution and normal-organ and tumor radiation dosimetry for Lu-177 DOTATATE administered concurrently with CAP/TEM. METHODS:: 20 patients with non-resectable histologically confirmed gastroenteropancreatic neuroendocrine tumors with normal kidney function, a normal haematological profile and somatostatin receptor expression of the tumor lesions, as scintigraphically assessed by a Ga-68 DOTANOC scan, were included in two groups-case group (n = 10) and control group (n = 10). Patients included in case group were those who were advised concomitant CAPTEM therapy by the treating medical oncologist. Patients were administered CAP orally at a dose of 600mg m-2 bovine serum albumin twice a day for 14 days starting 9 days prior to PRRT and oral TEM as a single dose at a dose of 75 mg m-2 was given concurrently for the last 5 days commencing on the day of PRRT (days 9-14). In the control group, patients were treated with Lu-177 DOTATATE only. For PRRT, 6.4 GBq-7.6 GBq (173-207 mCi) of Lu-177 DOTATATE was administered as infusion into each patient over 10-15 min in a solution with positively charged amino acids for renal protection. Dosimetric calculations were done using the HERMES software. RESULTS:: Physiological uptake of Lu-177 DOTATATE was seen in all patients in liver, spleen kidneys, and bone marrow. Radiation absorbed doses (mean ± standard deviation) were obtained as 0.29 ± 0.12 mGy/MBq for kidneys, 0.30 ± 0.18 mGy/MBq for liver, 0.63 ± 0.37 mGy/MBq for spleen, 0.019 ± 0.001 mGy/MBq for bone marrow and 3.85 ± 1.74 mGy/MBq for tumours in the case group and they were 0.31± 0.26, 0.24 ± 0.14, 0.64 ± 0.42, 0.017 ± 0.016, 5.6 ± 11.27 mGy/MBq in kidneys, liver, spleen, bone marrow and neuroendocrine tumour, respectively, in the control group. Mann-Whitney U test between the variables of two groups showed an insignificant difference (p > 0.05). CONCLUSIONS:: The authors demonstrated no significant difference between the tumor and organ doses with Lu-177 DOTATATE in the patients treated with and without concomitant chemotherapy. ADVANCES IN KNOWLEDGE:: To our knowledge, this is the first dedicated study exhibiting dosimetric analysis in patients undergoing PRRT in combination with chemotherapy.

Radiation Dose to the Occupational Worker during the Synthesis of 188Re-labeled Radiopharmaceuticals in the Nuclear Medicine Department.

AIM: The aim of this study is to estimate whole-body radiation dose to the radiopharmacist involved in labeling of three different 188Re-labeled compounds, namely, 188Re-Lipiodol, 188Re-tin colloid, and 188Re-hydroxyl-ethylidene-diphosphonate (HEDP) and to compare the occupational burden with the dose limits recommended by Atomic Energy Regulatory Board, India. MATERIALS AND METHODS: The Department of Nuclear Medicine at Fortis Memorial Research Institute currently synthesizes three different Rhenium-188 labeled compounds, namely, 188Re-Lipiodol, 188Re-HEDP, and 188Re-tin colloid. To estimate the radiation exposure to the radiopharmacist involved in the synthesis, a survey meter was used to measure radiation level before the start of labeling procedure in the radiopharmacy by keeping it at the location where the radiopharmacist normally stands during preparation. Data were collected for 6 syntheses of each 188Re-Lipiodol, 4 for 188Re-HEDP, and 3 for 188Re-tin colloid followed by the quality control. The pocket dosimeter was used by the radiopharmacistat chest level, performing the labeling of 188Re-labeled compounds. All radiopharmaceuticals were synthesized by a single radiopharmacist. RESULTS: 1850 MBq (50 mCi) 188W-188Re generator was eluted before the preparation of each radiopharmaceutical. The amount of 188ReO4- used for labeling with lipiodol/4-hexadecyl-1,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol, HEDP, and Tin colloid was in the range of 3182-4440 MBq (86-120 mCi), 2812-3774 MBq (76-102 mCi), and 962-1295 MBq (26-35 mCi), respectively. Meantime required to complete the synthesis was 95, 40, and 131.5 min, respectively. Mean whole-body effective dose received was 0.052, 0.009, and 0.004 mSv, respectively, as measured by using the pocket dosimeter. CONCLUSION: From this small study, we observed that the whole-body radiation dose to the radiopharmacist in radiolabeling and quality control of 188Re-labeled radiopharmaceuticals is within prescribed limits at the current synthesis frequency.

Rare Sites of Metastases in Prostate Cancer Detected on Ga-68 PSMA PET/CT Scan-A Case Series.

Ga-68 labeled prostate-specific membrane antigen (PSMA) whole body PET/CT scan is a novel upcoming modality for the evaluation of prostate cancer. We present three cases of prostate cancer showing rare sites of metastases like brain, penis, and liver detected on Ga-68 PSMA PET/CT scan thus emphasizing its role in lesion detection and staging.

Potential role of F18 FDG PET-CT as an imaging biomarker for the noninvasive evaluation in uncomplicated skeletal tuberculosis: a prospective clinical observational study.

PURPOSE: This is a prospective non-randomized observation study done on 33 patients with uncomplicated spinal tuberculosis to observe the imaging characteristics on sequential F-18 FDG PET CT scans. METHODS: 33 consecutive patients with pathologically proven spinal tuberculosis underwent a baseline contrast-enhanced whole body FDG PET scan before initiation of antitubercular therapy, 6 and 12 months and at 18 months or the end of antitubercular therapy. RESULT: The baseline peak SUVmax of lesions in our 33 cases had values ranging from 5.9 to 30.3 (mean 14.8). 63.6 % patients had clinically occult non-contiguous multifocal skeletal involvement at the time of the baseline whole body PET CT scanning. The mean change in SUVmax at various time points was highly significant (p value < 0.001). CONCLUSION: SUVmax can be taken as a reliable marker for serial quantification of metabolic activity in spinal tuberculosis. This may translate into a potential role for FDG as an imaging biomarker for noninvasive response evaluation in skeletal tuberculosis.