Isothiocyanate-Functionalized Bifunctional Chelates and fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) Complexes for Targeting uPAR in Prostate Cancer.
Isothiocyanate-Functionalized Bifunctional Chelates and fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) Complexes for Targeting uPAR in Prostate Cancer.
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DOI：
10.1021/acs.bioconjchem.5b00531
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发表时间：
2016-01-20
影响因子：
4.7
通讯作者：
Benny, Paul D.
中科院分区：
文献类型：
--
作者：
Kasten, Benjamin B.;Ma, Xiaowei;Cheng, Kai;Bu, Lihong;Slocumb, Winston S.;Hayes, Thomas R.;Trabue, Steven;Cheng, Zhen;Benny, Paul D.
Developing new strategies to rapidly incorporate the fac-[MI(CO)3]+ (M = Re, 99mTc) core into biological targeting vectors in radiopharmaceuticals continues to expand as molecules become more complex and as efforts to minimize nonspecific binding increase. This work examines a novel isothiocyanate-functionalized bifunctional chelate based on 2,2′-dipicolylamine (DPA) specifically designed for complexing the fac-[MI(CO)3]+ core. Two strategies (postlabeling and prelabeling) were explored using the isothiocyanate-functionalized DPA to determine the effectiveness of assembly on the overall yield and purity of the complex with amine containing biomolecules. A model amino acid (lysine) examined (1) amine conjugation of isothiocyanate-functionalized DPA followed by complexation with fac-[MI(CO)3]+ (postlabeling) and (2) complexation of fac-[MI(CO)3]+ with isothiocyanate-functionalized DPA followed by amine conjugation (prelabeling). Conducted with stable Re and radioactive 99mTc analogs, both strategies formed the product in good to excellent yields under macroscopic and radiotracer concentrations. A synthetic peptide (AE105) which targets an emerging biomarker in CaP prognosis, urokinase-type plasminogen activator receptor (uPAR), was also explored using the isothiocyanate-functionalized DPA strategy. In vitro PC-3 (uPAR+) cell uptake assays with the 99mTc-labeled peptide (8a) showed 4.2 ± 0.5% uptake at 4 h. In a murine model bearing PC-3 tumor xenografts, in vivo biodistribution of 8a led to favorable tumor uptake (3.7 ± 0.7% ID/g) at 4 h p.i. with relatively low accumulation (<2% ID/g) in normal organs not associated with normal peptide excretion. These results illustrate the promise of the isothiocyanate-functionalized approach for labeling amine containing biological targeting vectors with fac-[MI(CO)3]+.
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影响因子：
46.2
作者：
Jewett JC;Bertozzi CR
通讯作者：
Bertozzi CR
影响因子：
--
作者：
Al-Janabi, Omar;Taubert, Helge;Fuessel, Susanne
通讯作者：
Fuessel, Susanne
影响因子：
4.9
作者：
Ganguly, Tanushree;Kasten, Benjamin B.;Benny, Paul D.
通讯作者：
Benny, Paul D.
影响因子：
14.8
作者：
Cooper, Maggie S.;Sabbah, Emmanuelle;Mather, Stephen J.
通讯作者：
Mather, Stephen J.
影响因子：
3.1
作者：
Armstrong, Andrea F.;Lemon, Jennifer A.;Valliant, John F.
通讯作者：
Valliant, John F.