Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Nucl Med. 2006 Dec;47(12):2042-7.

Development of a novel 99mTc-chelate-conjugated bisphosphonate with high affinity for bone as a bone scintigraphic agent.

Author information

  • 1Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.

Abstract

In bone scintigraphy using (99m)Tc with methylenediphosphonate ((99m)Tc-MDP) and hydroxymethylenediphosphonate ((99m)Tc-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 (99m)Tc-mercaptoacetylglycylglycylglycine (MAG3)-conjugated hydroxy-bisphosphonate (HBP) ((99m)Tc-MAG3-HBP) and a (99m)Tc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-conjugated hydroxy-bisphosphonate ((99m)Tc-HYNIC-HBP).

METHODS:

(99m)Tc-MAG3-HBP was prepared by complexation of MAG3-HBP with (99m)Tc using SnCl(2) as a reductant. The precursor of (99m)Tc-HYNIC-HBP, HYNIC-HBP, was obtained by deprotection of the Boc group after the coupling of Boc-HYNIC to a bisphosphonate derivative. (99m)Tc-HYNIC-HBP was prepared by a 1-pot reaction of HYNIC-HBP with (99m)TcO(4)(-), tricine, and 3-acetylpyridine in the presence of SnCl(2). Affinity for bone was evaluated in vitro by hydroxyapatite-binding assays for (99m)Tc-HMDP, (99m)Tc-MAG3-HBP, and (99m)Tc-HYNIC-HBP. Biodistribution experiments for the 3 (99m)Tc-labeled compounds were performed on normal rats.

RESULTS:

(99m)Tc-MAG3-HBP and (99m)Tc-HYNIC-HBP were each prepared with a radiochemical purity of >95%. In the in vitro binding assay, (99m)Tc-MAG3-HBP and (99m)Tc-HYNIC-HBP had greater affinity for hydroxyapatite than (99m)Tc-HMDP. In the biodistribution experiments, (99m)Tc-MAG3-HBP and (99m)Tc-HYNIC-HBP had higher levels of radioactivity in bone than (99m)Tc-HMDP. (99m)Tc-MAG3-HBP was cleared from the blood slower than (99m)Tc-HMDP, whereas there was no significant difference in clearance between (99m)Tc-HYNIC-HBP and (99m)Tc-HMDP. Consequently, (99m)Tc-HYNIC-HBP showed a higher bone-to-blood ratio than (99m)Tc-HMDP.

CONCLUSION:

We developed a novel (99m)Tc-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 (99m)Tc-HYNIC-HBP holds great potential for bone scintigraphy.

PMID:
17138748
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire
    Loading ...
    Write to the Help Desk