RP463: A Stabilized Technetium-99m Complex of a Hydrazino Nicotinamide Derivatized Chemotactic Peptide for Infection Imaging
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- 作者：D. Scott Edwards ; Shuang Liu ; Marisa C. Ziegler ; Anthony R. Harris ; Andrew C. Crocker ; Stuart J. Heminway ; John A. Barrett ; Gary J. Bridger ; Michael J. Abrams ; and John D. Higgins ; III
- 刊名：Bioconjugate Chemistry
- 出版年：1999
- 出版时间：September 1999
- 年：1999
- 卷：10
- 期：5
- 页码：884 - 891
- 全文大小：186K
- 年卷期：v.10,no.5(September 1999)
- ISSN：1520-4812
文摘
A HYNIC-conjugated chemotactic peptide (fMLFK-HYNIC) was labeled with 99mTc using tricine andTPPTS as coligands. The combination of fMLFK-HYNIC, tricine, and TPPTS with 99mTc produced aternary ligand complex [99mTc(fMLFK-HYNIC)(tricine)(TPPTS)] (RP463). RP463 was synthesized eitherin two steps, in which the binary ligand complex [99mTc(fMLFK-HYNIC)(tricine)2] (RP469) was formedfirst and then reacted with TPPTS, or in one step by direct reduction of [99mTc]pertechnetate withstannous chloride in the presence of fMLFK-HYNIC, tricine, and TPPTS. The radiolabeling yield forRP463 was usually 
90% using 10 
g of fMLFK-HYNIC and 100 mCi of [99mTc]pertechnetate. UnlikeRP469, which decomposed rapidly in the absence of excess tricine coligand, RP463 was stable in solutionfor at least 6 h. [99Tc]RP463 was prepared and characterized by HPLC and electrospray massspectrometry. In an in vitro assay, [99Tc]RP463 showed an IC50 of 2 nM against binding of [3H]fMLFto receptors on PMNs. [99Tc]RP463 also induces effectively the superoxide release of polymorphonuclearleukocytes (PMNs) with an EC50 value of 0.2 ± 0.2 nM. The localization of RP463 in the infection fociwas assessed in a rabbit infection model. RP463 was cleared from the blood faster than RP469 andwas excreted mainly through the renal system. As a result of rapid blood clearance and increaseduptake, the target-to-background ratios continuously increased from 1.5 ± 0.2 at 15 min postinjectionto 7.5 ± 0.4 at 4 h postinjection. Visualization of the infected area could be as early as 2 h. A transientdecrease in white blood cell count of 35% was observed during the first 30 min after injection of theHPLC-purified RP463 in the infected rabbit. This suggests that future research in this area shouldfocus on developing highly potent antagonists for chemotactic peptide receptor or other receptors onPMNs and monocytes.
90% using 10 g of fMLFK-HYNIC and 100 mCi of [99mTc]pertechnetate. UnlikeRP469, which decomposed rapidly in the absence of excess tricine coligand, RP463 was stable in solutionfor at least 6 h. [99Tc]RP463 was prepared and characterized by HPLC and electrospray massspectrometry. In an in vitro assay, [99Tc]RP463 showed an IC50 of 2 nM against binding of [3H]fMLFto receptors on PMNs. [99Tc]RP463 also induces effectively the superoxide release of polymorphonuclearleukocytes (PMNs) with an EC50 value of 0.2 ± 0.2 nM. The localization of RP463 in the infection fociwas assessed in a rabbit infection model. RP463 was cleared from the blood faster than RP469 andwas excreted mainly through the renal system. As a result of rapid blood clearance and increaseduptake, the target-to-background ratios continuously increased from 1.5 ± 0.2 at 15 min postinjectionto 7.5 ± 0.4 at 4 h postinjection. Visualization of the infected area could be as early as 2 h. A transientdecrease in white blood cell count of 35% was observed during the first 30 min after injection of theHPLC-purified RP463 in the infected rabbit. This suggests that future research in this area shouldfocus on developing highly potent antagonists for chemotactic peptide receptor or other receptors onPMNs and monocytes.