950887-97-5Relevant academic research and scientific papers
The synthesis of a 99mTc-labeled tetravalent targeting probe upon isonitrile coordination to 99mTcI for enhanced target uptake in saturable systems
Mizuno, Yuki,Uehara, Tomoya,Jen, Chun-Wei,Akizawa, Hiromichi,Arano, Yasushi
, p. 26126 - 26135 (2019)
The presence of excess unlabeled ligands in the injectate hinders the target uptake of 99mTc-labeled targeting vectors. To address the issue, we previously developed a chemical design which provides a 99mTc-labeled trivalent RGD probe upon CN-βAla-Gly-Gly-c(RGDfK) (Lβ) coordination to [99mTc][Tc(CO)3]+ core at pH 6.0. In this study, we extended our coordination mediated synthesis of the trivalent RGD probe to that of a tetravalent one. Our initial attempts reacting Lβ with [99mTc][Tc(CO)3]+ core at pH 8.0 failed to provide [99mTc][Tc(CO)2(Lβ)4]+ due to the formation of multiple side products. A γ-aminobutylic acid (GABA) based isonitrile ligand CN-GABA-Gly-Gly-c(RGDfK) (LG), on the other hand, avoided the side reaction and selectively provided [99mTc][Tc(CO)2(LG)4]+ (99mTc-[LG]4) at pH 8.0. 99mTc-[LG]4 exhibited higher binding affinity to integrin αvβ3 than its unlabeled ligand, and visualized U87MG tumor without tedious post-labeling purification. These results indicate that the metal coordination-mediated syntheses of 99mTc-labeled multivalent probes have been successfully applied to a tetravalent one, which would allow a wider range of choices for designing novel 99mTc-labeled multivalent probes of high in vivo target uptake.
Synthesis and Biological Evaluation of Novel 99mTc-Labeled Palbociclib Derivatives Targeting Cyclin-Dependent Kinase 4/6 (CDK4/6) as Potential Cancer Imaging Agents
Song, Xiaoqing,Gan, Qianqian,Zhang, Xuran,Zhang, Junbo
, p. 4213 - 4222 (2019)
Cancer results from cell proliferation that exceeds normal growth control. There are various specific proteins that control and regulate the cell cycle, such as cyclin-dependent kinases (CDKs), cyclins, and retinoblastoma protein (pRb). The aberration of the cyclin D-CDK4/6-INK4-pRb pathway occurs frequently in cancers; thus, CDK4/6 is an attractive target for the development of radiopharmaceuticals for tumor imaging. In this study, we chose palbociclib, which was approved by the FDA for treating ER+/HER2- advanced breast cancer as the target vector and the isonitrile group, which can coordinate strongly with the [99mTc(CO)3]+ core as the bifunctional chelator, to develop four novel 99mTc-labeled radiotracers for tumor imaging. The ligands (L2, L3, L4, and L5) were synthesized by reacting palbociclib with isocyanide-containing active esters and then radiolabeling with a [99mTc(CO)3]+ core to produce radiotracers (99mTc-L2, 99mTc-L3, 99mTc-L4, and 99mTc-L5) with high radiochemical purity (>95%) and good stability in vitro. The structures of the 99mTc complexes were identified by preparation and characterization of the corresponding stable rhenium complexes. Partition coefficient results indicated that these complexes were lipophilic. A kinase inhibition assay demonstrated the high affinity of the stable Re complexes for CDK4. A cell study showed that all four complexes had substantial uptake by MCF-7 cells and could be significantly inhibited by palbociclib and nonradiolabeled ligand, indicating a CDK4/6-specific uptake mechanism. Biodistribution studies in nude mice bearing MCF-7 tumors showed that the complexes had obvious accumulation in tumors at 2 h postinjection. 99mTc-L2 exhibited the highest tumor uptake and tumor/blood ratio, whereas 99mTc-L4 showed the highest tumor/muscle ratio. The micro-SPECT/CT study showed that complex 99mTc-L4 had visible uptake at the tumor site, and the accumulation was clearly reduced in the image after pretreatment with palbociclib, further indicating CDK4/6 specificity. All the results showed that the 99mTc-labeled complexes in this work have the potential for tumor imaging.
Evaluation and comparison of 99mTc-labeled d-glucosamine derivatives with different 99mTc cores as potential tumor imaging agents
Zhang, Xuran,Gan, Qianqian,Ruan, Qing,Xiao, Di,Zhang, Junbo
, (2020)
Isocyanide is a strong coordination ligand that can coordinate with [99mTc(I)(CO)3]+ core and [99mTc(I)]+ core to produce stable 99mTc complexes, therefore developing a 99mTc-lab
