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01-05-2013 | Original Article

Biological evaluation of 3-[¹⁸F]fluoro-α-methyl-d-tyrosine (d-[¹⁸F]FAMT) as a novel amino acid tracer for positron emission tomography

Authors: Yasuhiro Ohshima, Hirofumi Hanaoka, Hideyuki Tominaga, Yoshikatsu Kanai, Kyoichi Kaira, Aiko Yamaguchi, Shushi Nagamori, Noboru Oriuchi, Yoshito Tsushima, Keigo Endo, Noriko S. Ishioka

Published in: Annals of Nuclear Medicine | Issue 4/2013

Abstract

Objective

3-[¹⁸F]Fluoro-α-methyl-l-tyrosine (l-[¹⁸F]FAMT) is a useful amino acid tracer for positron emission tomography (PET) imaging of malignant tumors. Because d-amino acids are not well distributed in non-target organs and are rapidly excreted in urine, the d-isomer of [¹⁸F]FAMT could allow clear PET imaging of tumors early after administration. In this study, we prepared 3-[¹⁸F]fluoro-α-methyl-d-tyrosine (d-[¹⁸F]FAMT) and evaluated its usefulness.

Methods

d-[¹⁸F]FAMT was synthesized according to the method for preparation of l-[¹⁸F]FAMT. The in vitro and in vivo stability of [¹⁸F]FAMT were evaluated by high-performance liquid chromatography. Cellular uptake of [¹⁸F]FAMT was evaluated using LS180 colon adenocarcinoma cells. Biodistribution studies were performed in LS180 tumor-bearing mice, and the tumors were imaged using a small-animal PET scanner.

Results

The radiolabeling yield of d-[¹⁸F]FAMT was approximately 10 %, similar to that of l-[¹⁸F]FAMT. Over 95 % of d-[¹⁸F]FAMT remained intact in mice until 60 min after administration. d-[¹⁸F]FAMT was gradually taken up by the LS180 cells. Tumor uptake of d-[¹⁸F]FAMT was competitively inhibited by pretreatment with α-methyl-l-tyrosine, a selective substrate for the system l-amino acid transporter 1 (LAT1), suggesting the involvement of LAT1 in tumor uptake of d-[¹⁸F]FAMT. In biodistribution studies, d-[¹⁸F]FAMT showed rapid clearance from the blood, marked accumulation and retention in the tumor, and lower accumulation in non-target organs, especially kidney and pancreas, compared to l-[¹⁸F]FAMT. The amount of d-[¹⁸F]FAMT in the tumor was also reduced, and tumor-to-blood ratio and tumor-to-muscle ratio of d-[¹⁸F]FAMT were similar to those of l-[¹⁸F]FAMT at every time point. PET imaging with d-[¹⁸F]FAMT did not provide a clear image of the tumor early after administration. However, d-[¹⁸F]FAMT provided higher tumor-to-background contrast than l-[¹⁸F]FAMT.

Conclusions

d-[¹⁸F]FAMT showed rapid blood clearance, low accumulation in non-target organs, and tumor-selective imaging compared with l-[¹⁸F]FAMT. Thus, d-[¹⁸F]FAMT could potentially serve as a novel PET tracer for imaging malignant tumors.

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Title: Biological evaluation of 3-[18F]fluoro-α-methyl-d-tyrosine (d-[18F]FAMT) as a novel amino acid tracer for positron emission tomography
Authors: Yasuhiro Ohshima
Hirofumi Hanaoka
Hideyuki Tominaga
Yoshikatsu Kanai
Kyoichi Kaira
Aiko Yamaguchi
Shushi Nagamori
Noboru Oriuchi
Yoshito Tsushima
Keigo Endo
Noriko S. Ishioka
Publication date: 01-05-2013
Publisher: Springer Japan
Published in: Annals of Nuclear Medicine / Issue 4/2013
Print ISSN: 0914-7187
Electronic ISSN: 1864-6433
DOI: https://doi.org/10.1007/s12149-013-0687-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Biological evaluation of 3-[¹⁸F]fluoro-α-methyl-d-tyrosine (d-[¹⁸F]FAMT) as a novel amino acid tracer for positron emission tomography

Abstract

Objective

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

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