Evaluation of radiological and clinical efficacy of ^{90}Y-DOTATATE} therapy in patients with progressive metastatic midgut neuroendocrine carcinomas

Background: To evaluate the radiological and clinical therapeutic effectiveness of ^{90}Y-octreotate [DOTATATE] inpatients with progressive somatostatin receptor-positive midgut neuroendocrine carcinomas (GEPNETs). Material/Methods: The study group: 34 patients, with histological proven extensive non-resectable and progressive midgut GEP-NETs. Radionuclide therapy (^{90}Y-DOTATATE) was given i.v. with a mean activity per administration 3,82 GBq. Initial clinical tumor responses were assessed 6-7 weeks after therapy completion and then once 3-monthly. The objective tumor response was classified according to the RECIST, initially between 4-6 months and then after each of the 6 months interval. Results: At 6 months after treatment completion, radiological tumor response was observed in 6 subjects with PR (19%), 25 presented SD (78%) and single had PD (3%). Overall clinical response to therapy at 6 months follow-up was observed in 23 patients (68%), SD in 5 patients (15%) and PD in 6 (18%). A year after therapy radiological tumour response was seen in 11 patients (44%), SD had 12 subjects (44%) and DP was noted in 2 patients. Two years after completed therapy PR was seen in 6 patients (33%), SD in additional 11 subjects (61%), single patient had PD. Clinical response to treatment in terms of PR and SD were noted in 22 patients (88%) after 1 year and in 14 patients (87%) after 2 years. Median PFS was 20 months, while the median OS was 23 months. In the 6 patients with clinical PD within initial 6 months the median PFS was 6 months and OS 11 months, while in those with SD or PR PFS was 22 months and OS 26 months (P<0.05). Conclusions: Therapy with ^{90}Y-DOTATATE} is effective in terms of clinical response, however the radiological response measured by the RECIST criteria underestimates benefits of this type of therapy in patients with progressive somatostatin receptor-positive midgut neuroendocrine carcinomas

Preclinical pharmacokinetics, biodistribution, radiation dosimetry and toxicity studies required for regulatory approval of a phase I clinical trial with 111In-CP04 in medullary thyroid carcinoma patients

Introduction: From a series of radiolabelled cholecystokinin (CCK) and gastrin analogues, 111In-CP04 (111In-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) was selected for further translation as a diagnostic radiopharmaceutical towards a first-in-man study in patients with medullary thyroid carcinoma (MTC). A freeze-dried kit formulation for multicentre application has been developed. We herein report on biosafety, in vivo stability, biodistribution and dosimetry aspects of 111In-CP04 in animal models, essential for the regulatory approval of the clinical trial. Materials and methods: Acute and extended single dose toxicity of CP04 was tested in rodents, while the in vivo stability of 111In-CP04 was assessed by HPLC analysis of mouse blood samples. The biodistribution of 111In-CP04 prepared from a freeze-dried kit was studied in SCID mice bearing do

Initial direct comparison of 99mTc-TOC and 99mTc-TATE in identifying sites of disease in patients with proven GEP NETs

The imaging of neuroendocrine tumors has become one of the most significant areas in nuclear oncology. In an attempt to provide high-quality imaging and possible sensitivity at a reduced cost, time, and radiation dose, several (99m)Tc agents have been proposed. The aim of this initial study was to compare the tumor uptake and biodistribution of 2 new 6-hydrazinopyridine-3-carboxylic acid (HYNIC)-derivatized Tyr(3)-octreotide analogs, (99m)Tc-[HYNIC,Tyr(3)]octreotide ((99m)Tc-TOC) and (99m)Tc-[HYNIC,Tyr(3),Thr(8)]octreotide ((99m)Tc-TATE), in patients with somatostatin receptor-expressing tumors. METHODS: Each of 12 patients with proven gastrointestinal pancreatic neuroendocrine tumors received a mean activity of 520 MBq of (99m)Tc-TOC and (99m)Tc-TATE. Scintigraphy with both tracers was performed 3-4 h after their injection using standard whole-body and SPECT imaging. The images were reviewed subjectively by 2 readers, who reported tumor uptake lesion by lesion. RESULTS: Both radiotracers demonstrated concordance between the results in 7 patients (58%). In total, 110 sites of disease were identified with (99m)Tc-TOC, compared with 115 with (99m)Tc-TATE. There was 1 case in which (99m)Tc-TOC identified sites of disease not seen on (99m)Tc-TATE imaging but 4 cases in which some sites of disease were seen with (99m)Tc-TATE and not (99m)Tc-TOC. CONCLUSION: In this initial study, both tracers seem to show similar sites of tumor, with (99m)Tc-TATE having a slight edge in the total number of lesions seen, especially in lymph node metastases

Highlight selection of radiochemistry and radiopharmacy developments by editorial board

Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to update the readership on trends in the field of radiopharmaceutical development. Results: This commentary of highlights has resulted in 21 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals. Also the first contribution in relation to MRI-agents is included. Conclusions: Trends in (radio)chemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry. © 2021, The Author(s).Open Access funding enabled and organized by Projekt DEAL. Financial support from EJNMMI Radiopharmacy and Chemistry to make this review article available for Open Access is gratefully acknowledged

IAEA activities on 67Cu, 186Re, 47Sc Theranostic radionuclides and Radiopharmaceuticals

Despite interesting properties, the use of 67Cu, 186Re and 47Sc theranostic radionuclides in preclinical studies and clinical trials is curtailed by their limited availability due to a lack of widely established production methods. An IAEA Coordinated Research Project (CRP) was initiated to identify important technical issues related to the production and quality control of these emerging radionuclides and related radiopharmaceuticals, based on request from IAEA Member States. The international team worked on targetry, separation, quality control and radiopharmaceutical aspects of the radionuclides obtained from research reactors and cyclotrons leading to preparation of a standard recommendations for all Member States. The CRP was initiated in 2016 with fourteen participants from thirteen Member States from four continents. Extraordinary results on the production, quality control and preclinical evaluation of selected radionuclides were reported in this project that was finalized in 2020. The outcomes, outputs and results of this project achieved by participating Member States are described in this minireview