Preparation of DOTA-TATE and DOTA-NOC freeze-dried kits for formulation of patient doses of 177Lu-labeled agents and their comparison for peptide receptor radionuclide therapy application

Abstract

The objective of the present work is to prepare freeze-dried DOTA-TATE and DOTA-NOC kits for the easy and convenient preparation of patient doses of 177Lu-DOTA-TATE and 177Lu-DOTA-NOC, respectively at the hospital radiopharmacy and to compare the radio-peptides with respect to their radiochemical and biological behaviors. Freeze-dried kits of DOTA-TATE and DOTA-NOC, comprising a lyophilized mixture of 200 μg of DOTA-peptide, 80 mg of gentisic acid and 13.9 mg of ammonium acetate were prepared. Therapeutic doses of 177Lu-labeled peptides (up to 200 mCi, 7.4 GBq) were prepared using these kits and 177Lu, produced in-house, with >99 % radiochemical purity and high stability following an easy and convenient protocol. Comparative pharmacokinetic behavior of the radio-peptides was studied by carrying out biodistribution studies in normal Wistar rats which revealed higher retention of activity in several major organs and slower renal clearance for 177Lu-DOTA-NOC compared to that of 177Lu-DOTA-TATE. Preliminary pharmacokinetic studies, carried out in limited number of patients suffering from cancers of neuroendocrine origins, showed lower accumulation of activity in vital organs and faster renal clearance of 177Lu-DOTA-TATE compared to that of 177Lu-DOTA-NOC.