In vivo comparison of DOTA based 68Ga-labelled bisphosphonates for bone imaging in non-tumour models

Bone metastases are a class of cancerous metastases that result from the invasion of a tumor into bone. The solid mass which forms inside the bone is often associated with a constant dull ache and severe spikes in pain, which greatly reduce the quality of life of the patient. Numerous Tc-88m-labeled bisphosphonate functionalised complexes are well established tracers for bone metastases imaging. The objective of this research was to evaluate the pharmacokinetics and behaviour of three DOTA based bisphosphonate functionalised ligands (BPAMD, BPAPD and BPPED), using both Ga-68 mu-PET in vivo imaging and ex vivo biodistribution studies in healthy Wistar rats. The compounds were labelled with Ga-68 in high yields using an ammonium acetate buffer, and subsequently purified using a cation exchange resin. High bone uptake values were observed for all Ga-68-labelled bisphosphonates at 60 minutes p.i. The highest uptake was observed for [Ga-68]BPPED (2.6 +/- 0.3% ID/g) which compares favourably with that of [Tc-99m]MDP (2.7 +/- 0.1 ID/g) and [F-18]fluoride (2.4 +/- 0.2% ID/g). The Ga-68-labelled DOTA-bisphosphonates showed rapid clearance from the blood and renal system, as well as low binding to soft tissue, resulting in a high bone to blood ratio (9.9 at 60 minutes p.i. for [Ga-68]BPPED, for example). Although further studies are required to assess their performance in tumor models, the results obtained suggest that these ligands could be useful both in imaging (Ga-68) and therapeutic treatment (Lu-177) of bone metastases. (C) 2013 Elsevier Inc. All rights reserved.