Abstract
1945
Objectives Sine increased permeability of blood vessels is one of the features of diseased bone, a 99mTc-labeled compound of higher molecular size and higher hydroxyapatite (HA) binding than those of 99mTc-methylenediphosphonate (MDP) were designed, synthesized and evaluated as a radiopharmaceutical for targeting osteogenic region.
Methods The HA binding and apparent molecular size at neutral pH of oligo-aspartic acid increase with an increase in its chain length. The amine residues of two pentamers of D-aspartic acid (D-Asp)5 were conjugated with each of the two carboxylic acids of 99mTc-L,L-1,2-ethylenedicysteine (EC) to prepare 99mTc-EC-[(D-Asp)5]2. The permeability of membrane filter (10 kDa), HA binding of 99mTc-EC-[(D-Asp)5]2 were compared with those of 99mTc-MDP. Biodistribution of the two 99mTc-labeled compounds in mice was compared. The accumulation in bone regeneration sites of this compound were also compared with 99mTc-MDP in rat model.
Results The membrane permeability of 99mTc-EC-[(D-Asp)5]2 (20 %)was significantly lower than that of 99mTc-MDP (68 %). The HA binding of 99mTc-EC-[(D-Asp)5]2 was higher than that of 99mTc-MDP. 99mTc-EC-[(D-Asp)5]2 exhibited faster clearance from the blood and lower accumulation in normal bone of mice. In bone regeneration model, the regeneration to normal region ratios of 99mTc-EC-[(D-Asp)5]2 (ratio: 3.6) were significantly higher than those of 99mTc-MDP (ratio: 2.8).
Conclusions Although further optimization of chain length is required, the present molecular design would be useful to image osteogenic region of bone in short post-injection times.
- © 2009 by Society of Nuclear Medicine