Ga(III) chelates of amphiphilic DOTA-based ligands: synthetic route and in vitro and in vivo studies

Abstract

In this work, we report on a synthetic strategy using amphiphilic DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-based chelators bearing a variable-sized α-alkyl chain at one of the pendant acetate arms (from 6 to 14 carbon atoms), compatible with their covalent coupling to amine-bearing biomolecules. The amphiphilic behavior of the micelles-forming Ga(III) chelates (critical micellar concentration), their stability in blood serum and their lipophilicity (logP) were investigated. Biodistribution studies with the (67)Ga-labeled chelates were performed in Wistar rats, which showed a predominant liver uptake with almost no traces of the radiochelates in the body after 24 h.

Prospective of 68Ga-Radiopharmaceutical Development

“…QDs functionalized with such amphiphiles as RGD-C18, NOTA-C18, mannose-C18, lactose-C18, and labelled with 68 Ga were specifically accumulated in U87MG human glioma xenogratfs in mice 300. Micelle agents were formed by the aggregation of amphiphilic ligands comprising NOTA or DOTA coupled to an α-alkyl chain via acetate pendant arms 304, 305. Direct proportionality was found between the agent accumulation in rat liver and the length of the pendant α-alkyl chain and thus lipophilicity of the ligands 305.…”

“…Micelle agents were formed by the aggregation of amphiphilic ligands comprising NOTA or DOTA coupled to an α-alkyl chain via acetate pendant arms 304, 305. Direct proportionality was found between the agent accumulation in rat liver and the length of the pendant α-alkyl chain and thus lipophilicity of the ligands 305.…”

Synthesis,68Ga-Radiolabeling, and PreliminaryIn VivoAssessment of a Depsipeptide-Derived Compound as a Potential PET/CT Infection Imaging Agent

“…68 Ga-DOTA-TBIA101 was found stable in human blood, serum, and plasma against transchelation over 180 min (≥97.2%) as compared to 39% plasma binding of 68 Ga-DOTAVAP-P1 [ 20 ]. The stability of 68 Ga-DOTA-TBIA101 was determined by ITLC as successfully carried out by other workgroup studies that examined various tracer blood stabilities [ 26 – 29 ] but it might lack accuracy in determining potential metabolites. Conversely, HPLC was used by Ujula et al to assess DOTAVAP-P1 stability in human- and rat-plasma; the amount of intact product after 4 h of incubation was 88% and 87%, respectively.…”

Stem Cell Monitoring with a Direct or Indirect Labeling Method

“…DOTA is currently used in 64 Cu-diacetyl-bis(N4-methylthiosemicarbazone ( 64 Cu-ATSM), approved by the US Food and Drug Administration (FDA) in the USA. Therefore, the DOTA chelator is better clinically available and has a simple synthetic process [48]. 64 Cu can potentially be linked to the target, including peptides, antibodies, or nanoparticles, via a specified chelator system.…”