1045709-88-3Relevant academic research and scientific papers
Modular Synthesis of DOTA-Metal-Based PSMA-Targeted Imaging Agents for MRI and PET of Prostate Cancer
Schmitthenner, Hans F.,Dobson, Damien E.,Jones, Kelsea G.,Akporji, Nnamdi,Soika, Dana Q. M.,Nastiuk, Kent L.,Hornak, Joseph P.
, p. 13848 - 13854 (2019)
A practical, convergent synthesis of prostate-specific membrane antigen (PSMA) targeted imaging agents for MRI, PET, and SPECT of prostate cancer has been developed. In this approach, metals chelated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) were placed on the side chains of lysine early in the synthesis to form imaging modules. These are coupled to targeting modules, in this case consisting of the PSMA-binding urea DCL, bonded to an activated linker. The modular approach to targeted molecular imaging agents (TMIAs) offers distinct advantages. By chelating the MRI contrast metal Gd early, it doubles as a protecting group for DOTA. Standard coupling and deprotection steps may be utilized to assemble the modules into peptides, and the need for tri-tert-butyl protection of DOTA requiring removal by strong acid is averted. This enables mild conjugation of the imaging module to a wide variety of targeting agents in the final step. It was further discovered that two labile metals, La3+ or Ce3+, can be used as placeholders in DOTA during the synthesis, then transmetalated in mild acid by Cu2+, Ga3+, In3+, and Y3+, metals used in PET/SPECT. This enables the efficient synthesis of nonradioactive analogues of targeted molecular imaging agents that may be transported or stored until needed. A simple and mild two-step transmetalation, involving de-metalation in dilute acid, followed by rapid chelation of the radioactive metal, may be conveniently performed later at the clinic to provide the TMIAs for PET or SPECT.
Targeted biocompatible nanoparticles for the delivery of (-)-epigallocatechin 3-gallate to prostate cancer cells
Sanna, Vanna,Pintus, Gianfranco,Roggio, Anna Maria,Punzoni, Stefania,Posadino, Anna Maria,Arca, Alessandro,Marceddu, Salvatore,Bandiera, Pasquale,Uzzau, Sergio,Sechi, Mario
, p. 1321 - 1332 (2011/04/24)
Molecular targeted cancer therapy mediated by nanoparticles (NPs) is a promising strategy to overcome the lack of specificity of conventional chemotherapeutic agents. In this context, the prostate-specific membrane antigen (PSMA) has demonstrated a powerf
Synthesis and evaluation of technetium-99m- and rhenium-labeled inhibitors of the prostate-specific membrane antigen (PSMA)
Banerjee, Sangeeta R.,Foss, Catherine A.,Castanares, Mark,Mease, Ronnie C.,Byun, Youngjoo,Fox, James J.,Hilton, John,Lupold, Shawn E.,Kozikowski, Alan P.,Pomper, Martin G.
experimental part, p. 4504 - 4517 (2009/06/06)
The prostate-specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of cancer. We prepared seven 99mTc/Re-labeled compounds by attaching known Tc/Re chelating agents to an amino-functionalized PSMA inhibitor (lys-NHCONH-glu) with or without a variable length linker moiety. Ki values ranged from 0.17 to 199 nM. Ex vivo biodistribution and in vivo imaging demonstrated the degree of specific binding to engineered PSMA+ PC3 PIP tumors. PC3-PIP cells are derived from PC3 that have been transduced with the gene for PSMA. Despite demonstrating nearly the lowest PSMA inhibitory potency of this series, [99mTc(CO) 3(L1)]+ (L1 = (2-pyridylmethyl)2N(CH 2)4CH(CO2H)-NHCO-(CH2) 6CO-NH-lys-NHCONH-glu) showed the highest, most selective PIP tumor uptake, at 7.9 ± 4.0% injected dose per gram of tissue at 30 min postinjection. Radioactivity cleared from nontarget tissues to produce a PIP to flu (PSMA-PC3) ratio of 44:1 at 120 min postinjection. PSMA can accommodate the steric requirements of 99mTc/Re complexes within PSMA inhibitors, the best results achieved with a linker moiety between the ε amine of the urea lysine and the chelator.
