Document Detail

Assessment of 186Re chelate-conjugated bisphosphonate for the development of new radiopharmaceuticals for bones.
MedLine Citation:
PMID:  17210464     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: The preferable pharmacokinetics of rhenium-186 (186Re)-monoaminemonoamidedithiol-conjugated or 186Re-mercaptoacetyltriglycine-conjugated bisphosphonates (BPs) suggested that the molecular design would be applicable to other radionuclides such as 68Ga, 99mTc, 153Sm and 177Lu. In this study, a key factor affecting the pharmacokinetics of a chelate-conjugated BP was investigated to estimate the validity and the applicability of molecular design. METHODS: Chemically inert and well-characterized tricarbonyl[186Re][(cyclopentadienylcarbonyl amino)-acetic acid]rhenium ([186Re]CpTR-Gly) was conjugated with 3-amino-1-hydroxypropylidene-1,1-bisphosphonate and purified by high-performance liquid chromatography (HPLC) to prepare [186Re](1-{3-[tricarbonyl(cyclopentadienylcarbonyl amino)-acetylamido]-1-hydroxy-1-phosphono-propyl}-phosphonic acid)rhenium ([186Re]CpTR-Gly-APD). Plasma stability, plasma protein binding, hydroxyapatite (HA) binding and the pharmacokinetics of [186Re]CpTR-Gly-APD were compared with those of 186Re 1-hydroxyethylidene-1,1-diphosphonate (HEDP). The effect of HEDP coadministration and preadministration on the pharmacokinetics of [186Re]CpTR-Gly-APD was also determined. RESULTS: The HPLC-purified [186Re]CpTR-Gly-APD showed higher plasma stability, higher HA binding, higher bone accumulation and lower plasma protein binding than did 186Re-HEDP. However, HA binding of [186Re]CpTR-Gly-APD decreased to levels slightly higher than that of 186Re-HEDP at similar HEDP concentrations. Bone accumulation of [186Re]CpTR-Gly-APD also decreased to levels similar to that of 186Re-HEDP when [186Re]CpTR-Gly-APD was coinjected with HEDP equivalent to that in 186Re-HEDP. In contrast, HEDP pretreatment did not impair bone accumulation of the two 186Re-labeled compounds. However, a delay in blood clearance and an increase in renal radioactivity levels were observed particularly with 186Re-HEDP. CONCLUSIONS: Although 186Re-HEDP possessed HA binding and bone accumulation similar to those of [186Re]CpTR-Gly-APD, the specific activity of 186Re-labeled BPs was found to play a crucial role in bone accumulation and blood clearance. Thus, the molecular design of chelate-conjugated BP would be useful for the development of bone-seeking radiopharmaceuticals with a variety of radionuclides by selecting chelating molecules that provide high specific activities.
Tomoya Uehara; Zhe Long Jin; Kazuma Ogawa; Hiromichi Akizawa; Kazuyuki Hashimoto; Morio Nakayama; Yasushi Arano
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-11-16
Journal Detail:
Title:  Nuclear medicine and biology     Volume:  34     ISSN:  0969-8051     ISO Abbreviation:  Nucl. Med. Biol.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-09     Completed Date:  2007-04-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9304420     Medline TA:  Nucl Med Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  79-87     Citation Subset:  IM    
Graduate School of Pharmaceutical Sciences, Chiba University, Chuo-ku, Chiba 260-8675, Japan.
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MeSH Terms
Chelating Agents / chemistry
Diphosphonates / pharmacokinetics*,  therapeutic use
Drug Evaluation, Preclinical
Metabolic Clearance Rate
Organ Specificity
Radioisotopes / chemistry,  pharmacokinetics*,  therapeutic use
Radiopharmaceuticals / chemical synthesis,  pharmacokinetics,  therapeutic use
Rhenium / chemistry,  pharmacokinetics*,  therapeutic use
Tissue Distribution
Reg. No./Substance:
0/Chelating Agents; 0/Diphosphonates; 0/Radioisotopes; 0/Radiopharmaceuticals; 7440-15-5/Rhenium

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