PT - JOURNAL ARTICLE AU - Kazuma Ogawa AU - Takahiro Mukai AU - Yasuyuki Inoue AU - Masahiro Ono AU - Hideo Saji TI - Development of a Novel <sup>99m</sup>Tc-Chelate–Conjugated Bisphosphonate with High Affinity for Bone as a Bone Scintigraphic Agent DP - 2006 Dec 01 TA - Journal of Nuclear Medicine PG - 2042--2047 VI - 47 IP - 12 4099 - http://jnm.snmjournals.org/content/47/12/2042.short 4100 - http://jnm.snmjournals.org/content/47/12/2042.full SO - J Nucl Med2006 Dec 01; 47 AB - In bone scintigraphy using 99mTc with methylenediphosphonate (99mTc-MDP) and hydroxymethylenediphosphonate (99mTc-HMDP), it takes 2−6 h after an injection before imaging can start. This interval could be shortened with a new radiopharmaceutical with higher affinity for bone. Here, based on the concept of bifunctional radiopharmaceuticals, we designed a 99mTc-mercaptoacetylglycylglycylglycine (MAG3)-conjugated hydroxy-bisphosphonate (HBP) (99mTc-MAG3-HBP) and a 99mTc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-conjugated hydroxy-bisphosphonate (99mTc-HYNIC-HBP). Methods: 99mTc-MAG3-HBP was prepared by complexation of MAG3-HBP with 99mTc using SnCl2 as a reductant. The precursor of 99mTc-HYNIC-HBP, HYNIC-HBP, was obtained by deprotection of the Boc group after the coupling of Boc-HYNIC to a bisphosphonate derivative. 99mTc-HYNIC-HBP was prepared by a 1-pot reaction of HYNIC-HBP with 99mTcO4−, tricine, and 3-acetylpyridine in the presence of SnCl2. Affinity for bone was evaluated in vitro by hydroxyapatite-binding assays for 99mTc-HMDP, 99mTc-MAG3-HBP, and 99mTc-HYNIC-HBP. Biodistribution experiments for the 3 99mTc-labeled compounds were performed on normal rats. Results: 99mTc-MAG3-HBP and 99mTc-HYNIC-HBP were each prepared with a radiochemical purity of &gt;95%. In the in vitro binding assay, 99mTc-MAG3-HBP and 99mTc-HYNIC-HBP had greater affinity for hydroxyapatite than 99mTc-HMDP. In the biodistribution experiments, 99mTc-MAG3-HBP and 99mTc-HYNIC-HBP had higher levels of radioactivity in bone than 99mTc-HMDP. 99mTc-MAG3-HBP was cleared from the blood slower than 99mTc-HMDP, whereas there was no significant difference in clearance between 99mTc-HYNIC-HBP and 99mTc-HMDP. Consequently, 99mTc-HYNIC-HBP showed a higher bone-to-blood ratio than 99mTc-HMDP. Conclusion: We developed a novel 99mTc-chelate−conjugated bisphosphonate with high affinity for bone and rapid clearance from blood, based on the concept of bifunctional radiopharmaceuticals. The present findings indicate that 99mTc-HYNIC-HBP holds great potential for bone scintigraphy.