Abstract
1191
Objectives 177Lu labeled BPAMD [(4-{[bis-(phosphonomethyl)]carbamoyl}methyl)-7,10 bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl)acetic acid] has been used in patients with painful skeletal metastases. For a routinely application of 177Lu-BPAMD a stable labeling procedure as well as a robust quality control method which determines free 177Lu3+ and 177Lu-hydroxide, is required.
Methods The labelling procedure for the synthesis of 177Lu-BPAMD was performed under cGMP conditions using a laminar flow box. A solution of 2.4 mg 2,5 dihydroxy benzoic acid, 100-250 μg BPAMD in 300 μL sodium acetate buffer (0.4 M, pH = 5.5) was added to a solution of 6 GBq 177Lu-chloride in 300 μL 0.05 M HCl. The reaction mixture was heated for 30 minutes at 90 °C. After the reaction the mixture was diluted in 10 mL 0.9% saline solution, sterile filtered and samples were taken for quality control and sterility tests.
Results The radiochemical purity was greater than 95% as determined by radio HPLC (column: Alltech Universal Cation length 100 mm, ID 4.6 mm; solvent A: 0.2 M Na2HPO4/NaH2PO4, solvent B: 1 M citric acid, 0-10 min solvent A, 10-15 min solvent B, flow rate: 1.2 mL/min) The radio TLC was carried out using ITLC-SG and KG60 (solvent: 0.4 M sodium citrate). The addition of 2,5 dihydroxy benzoic acid as radical scavanger prevents radiolysis and leads to a higher stability of 177Lu-BPAMD. The final product is stable for more than 8 h.
Conclusions The stable labeling procedure and quality control protocol allows a routinely production and treatment of patients with skeletal metastases with 177Lu-BPAMD. The labeling delivers the product with a radiochemical purity higher than 95% and the final product is stable for more than 8 h. The HPLC method determines 177Lu3+ and formed colloidal hydroxides. The formation of 177Lu-hydroxide increases if smaller amounts of BPAMD were used. The formation of 177Lu-hydroxide as well as free 177Lu3+ in the final product is also detectable by radio TLC.