Development of a [177Lu]BPAMD labeling kit and an automated synthesis module for routine bone targeted endoradiotherapy

Cancer Biother Radiopharm. 2015 Mar;30(2):94-9. doi: 10.1089/cbr.2014.1720. Epub 2015 Feb 25.

Abstract

Painful bone lesions, both benign and metastatic, are often managed using conventional analgesics. However, the treatment response is not immediate and is often associated with side-effects. Radionuclide therapy is used for pain palliation in bone metastases as well as some benign neoplasms. Endoradiotherapy has direct impact on the pain-producing bone elements, and hence, response is significant, with minimal or no side-effects. A new potential compound for endoradiotherapy is [(177)Lu]BPAMD. It combines a highly affine bisphosphonate, covalently bridged with DOTA through an amide bond, with the low-energy β(-) emitting therapeutic radiolanthanide (177)Lu. For routine chemical application, an automated synthesis of this radiopharmaceutical and a Kit-type labeling procedure appears to be a basic requirement for its good manufacturing practice (GMP) based production. A Kit formulation combining BPAMD, acetate buffer, and ethanol resulted in almost quantitative labeling yields. The use of ethanol and ascorbic acid as quenchers prevented radiolysis over 48 hours. An automated synthesis unit was designed for the production of therapeutic doses of [(177)Lu]BPAMD up to 5 GBq. The procedure was successfully applied for patient treatments.

Keywords: bone metastases; endoradiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amides
  • Bone Neoplasms / radiotherapy*
  • Bone and Bones / radiation effects*
  • Diphosphonates / therapeutic use*
  • Humans
  • Lutetium / therapeutic use*
  • Male
  • Pain / radiotherapy
  • Radioisotopes / therapeutic use*
  • Radiopharmaceuticals / therapeutic use
  • Reagent Kits, Diagnostic
  • Staining and Labeling / methods

Substances

  • Amides
  • BPAMD ligand
  • Diphosphonates
  • Radioisotopes
  • Radiopharmaceuticals
  • Reagent Kits, Diagnostic
  • Lutetium