جستجوی مقالات مرتبط با کلیدواژه "dotatate" در نشریات گروه "پزشکی"

Peptide-based radiopharmaceuticals have great advantages that make them one of the most interesting radiotracers for theranostic applications. This study aims to develop [64Cu]Cu-DOTATATE as a beneficial agent for PET imaging of neuroendocrine tumors (NETs). 64Cu was produced via 68Zn(p,αn)64Cu reaction using 30 MeV Cyclotron. [64Cu]Cu-DOTATATE was prepared at optimized labeling conditions by varying parameters. The radiochemical purity of [64Cu]Cu-DOTATATE was checked by various methods. The stability of the final radiolabeled compound was assessed in PBS buffer and human serum. Binding affinity and internalization rate of [64Cu]Cu-DOTATATE were studied on the Rat C6 glioma cell line.  The biodistribution of [64Cu]Cu-DOTATATE was studied in normal and tumor-bearing rats at different intervals. Finally, the images were taken after the administration of the radiopharmaceutical by a dual-head SPECT system. [64Cu]Cu-DOTATATE was produced with radiochemical purity >99% (RTLC & HPLC) and specific activity of 22.4 GBq/mg in optimized conditions. [64Cu]Cu-DOTATATE demonstrated high stability in vitro and in vivo. The binding studies showed a high binding affinity of the radiopharmaceutical to somatostatin-receptor-expressing cells. The internalization studies showed >58% of the radiopharmaceutical is internalized into the C6 cells within 6 h after incubation. The biodistribution of [64Cu]Cu-DOTATATE in normal and tumor-bearing rats showed high uptake of somatostatin-receptor-expressing organs and tumors, respectively. The images of tumor-bearing rats were consistent with the results of the biodistribution study. Preclinical studies of [64Cu]Cu-DOTATATE showed that the radiopharmaceutical has a high potential for domestic use in  PET imaging of patients with NETs.

The objectives of this work was to assess the benefits of the application of Physiologically Based Pharmacokinetic (PBPK) models in patients with different neuroendocrine tumours (NET) who were treated with Lu-177 DOTATATE. The model utilises clinical data on biodistribution of radiolabeled peptides (RLPs) obtained by whole body scintigraphy (WBS) of the patients.
The blood flow restricted (perfusion rate limited) type of the PBPK model for biodistribution of radiolabeled peptides (RLPs) in individual human organs is based on the multi-compartment approach, which takes into account the main physiological processes in the organism: absorption, distribution, metabolism and excretion (ADME). The approach calibrates the PBPK model for each patient in order to increase the accuracy of the dose estimation. Datasets obtained using WBS in four patients have been used to obtain the unknown model parameters. The scintigraphic data were acquired using a double head gamma camera in patients with different neuroendocrine tumours who were treated with Lu-177 DOTATATE. The activity administered to each patient was 7400MBq.
Satisfactory agreement of the model predictions with the data obtained from the WBS for each patient has been achieved.
The study indicates that the PBPK model can be used for more accurate calculation of biodistribution and absorbed doses in patients. This approach is the first attempt of utilizing scintigraphic data in PBPK models, which was obtained during Lu-177 peptide therapy of patients with NET.

Optimized production and quality control of 68Ga-DOTATATE as an efficient and preferable PET radiotracer for somatostatin receptor imaging in neuroendocrine tumors is of great interest. In this study effort has been made to present a fast, efficient, cost-effective and facile protocol for 68Ga-DOTATATE productions for clinical trials. 68Ga-DOTATATEwas prepared using generator-based [68Ga] GaCl3 and DOTATATE at optimized conditions for time, temperature, ligand amount, gallium content and column cartridge purification followed by proper formulation. The biodistribution of the tracer in rats was studied using tissue counting and PET/CT imaging up to 120 min. 68Ga-DOTATATE was prepared at optimized conditions in 7-10 min at 95°C followed by SPE using C18 cartridge (radiochemical purity»99±0. 88% ITLC, >99% HPLC, specific activity: 1200-1850 MBq/nM). The biodistribution of the tracer demonstrated high kidney uptake of the tracer in 10-20 min consistent with reported somatostatin receptor mappings. The entire production and quality control of 68Ga-DOTATATE is presented including labeling, purification, HPLC analysis, sterilization and LAL test) took 18-20 min with significant specific activity for administration to limited number of patients in a PET center.

Peptide Receptor Radionuclide Therapy (PRRT) with yttrium-90 (90Y) and lutetium-177 (177Lu)-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system. All syntheses were carried out using the Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany). Sterile, GMP-certified, no-carrier added (NCA) 177Lu was used with GMPcertifiedpeptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLCSG and HPLC methods. A total of 17 [177Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [177Lu]-DOTATATE produced by each synthesis varied between 10-40 GBq and was dependant on the number of patients being treated on a given day. Thirteen individuals received a total of 37 individual treatment administrations in this period. There were no issues and failures with the system or the synthesis cassettes. The average radiochemical purity as determined by ITLC was above 99% (99.8 ± 0.05%) and the average radiochemical purity as determined by HPLC technique was above 97% (97.3 ± 1.5%) for this period. The automated synthesis of [177Lu]-DOTATATE using Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE peptide benefiting from the use of NCA 177Lu and almost negligible radiation exposure of the operators.

Gallium‐68 (Ga‐68) is an ideal research and hospital‐based PET radioisotope. Currently, the main form of Ga‐68 radiopharmaceutical that is being synthesised in‐house is Ga‐68 conjugated with DOTA based derivatives. The development of automated synthesis systems has increased the reliability, reproducibility and safety of radiopharmaceutical productions. Here we report on our three year, 500 syntheses experience with an automated system for Ga‐68 DOTATATE. The automated synthesis system we use is divided into three parts of a) servomotor modules, b) single use sterile synthesis cassettes and, c) a computerized system that runs the modules. An audit trail is produced by the system as a requirement for GMP production. The required reagents and chemicals are made in‐. The Germanium breakthrough is determined on a weekly basis. Production yields for each synthesis are calculated to monitor the performance and efficiency of the synthesis. The quality of the final product is assessed after each synthesis by ITLC‐SG and HPLC methods. A total of 500 Ga‐68 DOTATATE syntheses (>800 patient doses) were performed between March 2011 and February 2014. The average generator yield was 81.3±0.2% for 2011, 76.7±0.4% for 2012 and 75.0±0.3% for 2013. Ga‐68 DOTATATE yields for 2011, 2012, and 2013 were 81.8±0.4%, 82.2±0.4% and 87.9±0.4%, respectively. These exceed the manufacturer’s expected value of approximately 70%. Germanium breakthrough averaged 8.6×10‐6% of total activity which is well below the recommended level of 0.001%. The average ITLC‐measured radiochemical purity was above 98.5% and the average HPLC‐measured radiochemical purity was above 99.5%. Although there were some system failures during synthesis, there were only eight occasions where the patient scans needed to be rescheduled. In our experience the automated synthesis system performs reliably with a relatively low incident of failures. Our system had a consistent and reliable Ga‐68 DOTATATE output with high labelling efficiency and purity. There is minimal operator intervention and radiation exposure. The system is GMP‐compliant and has low maintenance and acceptable running costs. This system together with the recommended 68Ge/68Ga generator is well suited for use in a hospital‐based radiopharmacy