Metal Based Imaging Probes of DO3A-Act-Met for LAT1 Mediated Methionine Specific Tumors : Synthesis and Preclinical Evaluation

Abstract

DO3A-Act-Met, a methionine conjugated probe is a promising agent for targeted molecular imaging, exhibiting high specificity towards tumor owing to its essential role in proliferation of cancer cells mediated through LAT1.

Picolinic acid based acyclic bifunctional chelating agent and its methionine conjugate as potential SPECT imaging agents: syntheses and preclinical evaluation

“…The retention of 99m Tc-pentapa-en-met 2 in liver was for a longer period possibly because it is the inherent nature of amino acids based derivative to metabolise in the liver. 8 The uptake of 99m Tc-pentapa-en-met 2 conjugate in the other nontarget organs got signicantly lower than the chelate as conjugation with methionine changed its nal chemical properties which corroborated to the decreased accumulation in nontarget organs along with a fast clearance rate from the organs. The accumulation in the target organ tumor was there for a longer time period.…”

“…Yield: 84.5%. (8). Compound 7 (2.0 g, 4.11 mmol) was dissolved in tri-uoroacetic acid (2.0 mL) at 0 C with gentle stirring.…”

“…7 11 C-Methionine is one of the most useful biomarkers for the PET imaging of various cancers; however, due to the limitation of a short half-life of 20.3 min and the requirement of an onsite cyclotron to produce 11 C, a range of methionine derivatives have been developed for tumor imaging with the radioactive element having a longer half-life. 8 Thus, it was thought worthwhile to assess the application of a developed agent as BFC in targeted imaging by conjugating it with L-methionine. The methionine conjugate of the chelate was radiolabeled with 99m Tc to investigate its tumor targeting efficacy.…”

Evaluation of methionine and tryptophan derivatised vehicles: Met-ac-TE3A/Trp-ac-TE3A for tumor imaging

“…The range of concentrations were determined on the basis of our previous studies for such vehicle based ligand system for SPECT. [14][15][16] Signicant toxicity was not observed at lower concentrations for Met-ac-TE3A, which showed concentrationdependent cytotoxicity. It was observed that at a concentration of 0.1 mM Met-ac-TE3A at 2 h treatment resulted in lyses of 40% of U-87MG cells.…”

Comparative evaluation of Bis(thiosemicarbazone)- Biotin and Met-ac-TE3A for tumor imaging

“…Two of the most important chelators studied were DOTA and TETA [13]. In continuation of our work for design of novel agents having these vehicles, we previously synthesized DTPA-bis(methionine) [14] and DO3A-ActMet [15] and evaluated for imaging applications. Recently we have evaluated two novel amino acids (methionine and tryptophan) appended 1,4,8,11-tetraazacyclotetradecane triacetate (TE3A) compounds Met-ac-TE3A and Trp-ac-TE3A for tumor imaging in which Met-ac-TE3A showed very promising results for further evaluations [16].…”