The Synthesis and Evaluations of the⁶⁸Ga-Lissamine Rhodamine B (LRB) as a New Radiotracer for Imaging Tumors by Positron Emission Tomography

Abstract

Purpose. The aim of this study is to synthesize and evaluate 68Ga-labeled Lissamine Rhodamine B (LRB) as a new radiotracer for imaging MDA-MB-231 and MCF-7 cells induced tumor mice by positron emission tomography (PET). Methods. Firstly, we performed the radio synthesis and microPET imaging of 68Ga(DOTA-LRB) in athymic nude mice bearing MDA-MB-231 and MCF-7 human breast cancer xenografts. Additionally, the evaluations of 18F-fluorodeoxyglucose (FDG), as a glucose metabolism radiotracer for imaging tumors in the same xenografts, have been conducted as a comparison. Results. The radiochemical purity of 68Ga(DOTA-LRB) was >95%. MicroPET dynamic imaging revealed that the uptake of 68Ga(DOTA-LRB) was mainly in normal organs, such as kidney, heart, liver, and brain and mainly excreted from kidney. The MDA-MB-231 and MCF-7 tumors were not clearly visible in PET images at 5, 15, 30, 40, 50, and 60 min after injection of 68Ga(DOTA-LRB). The tumor uptake values of 18F-FDG were 3.79 ± 0.57 and 1.93 ± 0.48%ID/g in MDA-MB-231 and MCF-7 tumor xenografts, respectively. Conclusions. 68Ga(DOTA-LRB) can be easily synthesized with high radiochemical purity and stability; however, it may be not an ideal PET radiotracer for imaging of MDR-positive tumors.

Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

“…72–81 Small molecule heterocyclic cations were also used as vehicles to deliver other compounds to mitochondria. 82–92 The heterocyclic cations have been conjugated with quinone, spin traps, or thiol-reactive moieties to specifically localize those compounds in cell mitochondria. It was demonstrated that the uptake of rhodamine-linked compounds can be further increased by the addition of the lipophilic tetraphenylborate anion.…”

“…Many small molecule lipophilic cations (e.g., rhodamine, pyridinium, and cyanine derivatives) have been shown to accumulate in cell mitochondria. − Rhodamine- and cyanine-based cationic fluorophores have been extensively used as research tools as mitochondrial stains and for monitoring mitochondrial membrane potential, as discussed below, based on the extent of their total cellular uptake or the ratio of mitochondrial to cytosolic concentration of the cationic probe. − Small molecule heterocyclic cations were also used as vehicles to deliver other compounds to mitochondria. − The heterocyclic cations have been conjugated with quinone, spin traps, or thiol-reactive moieties to specifically localize those compounds in cell mitochondria. It was demonstrated that the uptake of rhodamine-linked compounds can be further increased by the addition of the lipophilic tetraphenylborate anion .…”

Anti-cancer potential of substituted “amino-alkyl-rhodamine” derivatives against MCF-7 human breast cancer cell line

“…These xanthene based dyes, which exhibit excellent spectroscopic characteristics such as large molar extinction coe cient, high emission quantum yield, absorption and emission at longer wavelengths, are therefore tuned to facilitate in vitro and/or in vivo monitoring of various chemical and biological species exploiting their contrast structure-function relation. The uorescence output of Fluorescein type dyes is pH sensitive and bleaches quickly, thus, its applicability gets restricted in a variety of applications (Li et al 2016). On contrary, rhodamine based dyes become a preferable choice as labelling agents considering the tuneable uorescence output, and ease of synthesis and functionalisation.…”