Radiosynthesis and preliminary biological evaluation of N-(2-[18F]fluoropropionyl)-L-glutamine as a PET tracer for tumor imaging

Abstract

In this study, radiosynthesis and biological evaluation of a new [18F]labeled glutamine analogue, N-(2-[18F]fluoropropionyl)-L-glutamine ([18F]FPGLN) for tumor PET imaging are performed. [18F]FPGLN was synthesized via a two-step reaction sequence from 4-nitrophenyl-2-[18F]fluoropropionate ([18F]NFP) with a decay-corrected yield of 30 ± 5% (n=10) and a specific activity of 48 ± 10 GBq/μmol after 125 ± 5 min of radiosynthesis. The biodistribution of [18F]FPGLN was determined in normal Kunming mice and high uptake of [18F]FPGLN was observed within the kidneys and quickly excreted through the urinary bladder. In vitro cell experiments showed that [18F]FPGLN was primarily transported by Na+-dependent system XAG− and was not incorporated into proteins. [18F]FPGLN displayed better stability in vitro than that in vivo. PET/CT studies revealed that intense accumulation of [18F]FPGLN were shown in human SPC-A-1 lung adenocarcinoma and PC-3 prostate cancer xenografts. The results support that [18F]FPGLN seems to be a possible PET tracer for tumor imaging.

Development and Biological Evaluation of the First Highly Potent and Specific Benzamide-Based Radiotracer [18F]BA3 for Imaging of Histone Deacetylases 1 and 2 in Brain

“…Both processes would be disadvantageous for imaging by PET. In contrast, the 2-[ 18 F]fluoropropanoyl group is used frequently for PET tracer design, due to higher metabolic stability [ 44 , 45 , 46 , 47 ]. Additionally, it is expected to have a low impact on biological activity due to its small size.…”

Radiosynthesis of novel N‐18F‐labeled 18F‐FHex‐α‐l‐Glu and 18F‐FHex‐β‐Glu

“…13,14 In our previous studies, we designed and synthesized 18 F and 11 C-labeled N-position acetyl amino acid analogs, such as 18 F-FPMET, 18 F-FPGln, 18 F-FPGlu, and 11 C-MGlu. 10,15,16 Among them, 18 F-FPGlu as a glutamate derivative showed apparent uptake in tumor tissues and low background in S180 fibrosarcoma, SPC-A-1, and LTEP-a-2 human lung adenocarcinoma mice models in tumors. 10 However, 18 F-FPGLU was metabolized in vivo, possibly due to the cleavage of peptide-bond.…”

Automated synthesis ofN-(2-[18F]Fluoropropionyl)-l-glutamic acid as an amino acid tracer for tumor imaging on a modified [18F]FDG synthesis module

“…Compared with [ 18 F]FDG, amino acid tracers have some advantages over [ 18 F]FDG in PET imaging of brain tumors, neuroendocrine tumors, and prostate cancer . Recently, several N ‐substituted 18 F‐labeled amino acid derivatives were developed in our research group and exhibited high tumor to background (T/B) contrast and favorable pharmacokinetics in vivo . Among these amino acid tracers, N ‐(2‐[ 18 F]fluoropropionyl)‐ l ‐glutamic acid ([ 18 F]FPGLU) as a typical example of N ‐ 18 F‐labeled amino acid tracers showed high tumor uptake and good T/B ratios in the mice bearing S180 fibrosarcoma, SPCA‐1, and LTEP‐a‐2 human lung adenocarcinoma, which could be translated into clinical use in the near future.…”