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J Nucl Med. 2008; 49 (Supplement 1):297P
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Radiopharmaceutical Chemistry: New Chemistry-Other

New Chemistry-Other Posters

Novel osteoclast-targeting agents for bone metastases

Wei Liu1, Asghar Hajibeigi1, Chandima Siyambalapitiyage1, Mai Lin1, Cynthia Rostollan1, Orhan Oz1, Zoltan Kovacs2 and Xiankai Sun1

1 Radiology; 2 Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, Texas


Formula

1264

Objectives: The skeleton is a preferential site of cancer metastases. Once the tumor spreads to the bone, it becomes unresponsive to standard therapeutic regimens. Bisphosphonates (BPs) are commonly used in the treatment of bone diseases. It has been shown that BPs preferentially accumulate in osteoclasts, which are overexpressed in both osteoblastic and osteolytic bone metastases mainly caused by breast and prostate cancers. Thus targeting osteoclasts may provide a new strategy to develop novel agents for the early detection and thus more efficient therapy of bone metastases. Here we report a new class of such compounds featuring a bifunctional chelator and an osteoclast-targeting moiety.

Methods: The hybrid agents (DO3A-BPs)were synthesized by conjugating DOTA with a bisphosphonate via various alkyl linkages. They were then labeled with 111In or 177Lu. The in vitro studies were performed on mouse bone marrow derived cells grown with or without RANKL and M-CSF ligands. The radiolabeled compounds were also evaluated in vivo.

Results: The new agents were fully characterized and then labeled with 111In and 177Lu. The in vitro studies showed elevated uptake of 111In-DO3A-BP in osteoclasts compared to the undifferentiated adherent bone marrow derived cells. The radiolabeled complexes exhibited favorable in vivo biodistribution profiles in normal mice with high bone uptake and long retention, rapid renal clearance, and low or negligible uptake in non-target organs.

Conclusions: A new group of bone-seeking agents has designed and synthesized. Preliminary in vitro and in vivo data have demonstrated their potential to be used for osteoclast-targeted diagnosis and therapy of bone metastases.

Research Support: This project is partially supported by NIH CA119219(Sun).





This Article
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Right arrow Articles by Sun, X.