In vivo measurement and characterization of a novel formulation of [[177]Lu]-DOTA-octreotate

Objective[s]: Lutetium-177 can be made with high specific activity and with no other isotopes of lutetium present, referred to as "No Carrier Added" [NCA] [177]Lu. We have radiolabelled DOTA-conjugated peptide DOTA-[Tyr[3]]-octreotate with NCA 177Lu ["NCA-LuTATE"] and used it in nearly 40 therapeutic administrations for subjects with neuroendocrine tumours or meningiomas. In this paper, we report on our initial studies on aspects of the biodistribution and dosimetry of NCA-LuTATE from gamma camera 2D whole body [WB] and quantitative 3D SPECT [qSPECT] [177]Lu imaging

Methods: Thirteen patients received 39 NCA-LuTATE injections. Extensive WB planar and qSPECT imaging was acquired at approximately 0.5, 4, 24 and 96 h to permit estimates of clearance and radiation dose estimation using MIRD-based methodology [OLINDA-EXM]

Results: The average amount of NCA-Lutate administered per cycle was 7839 +/- 520 MBq. Bi-exponential modelling of whole body clearance showed half lives for the fast and slow components of t[1/2]=2.1 +/- 0.6 h and t[1/2]=58.1 +/- 6.6 h respectively. The average effective dose to kidneys was 3.1 +/- 1.0 Gy per cycle. In eight patients completing all treatment cycles the average total dose to kidneys was 11.7 +/- 3.6 Gy

Conclusions: We have shown that NCA-LuTATE has an acceptable radiation safety profile and is a suitable alternative to Carrier-Added [177]Lu formulations. The fast component of the radiopharmaceutical clearance was closely correlated with baseline renal glomerular filtration rate, and this had an impact on radiation dose to the kidneys. In addition, it has less radioactive waste issues and requires less peptide per treatment

Gallium-68 DOTATATE production with automated PET radiopharmaceutical synthesis system: a three year experience

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