Evaluation of D-isomers of 4-borono-2-18F-fluoro-phenylalanine and O-11C-methyl-tyrosine as brain tumor imaging agents: a comparative PET study with their L-isomers in rat brain glioma.

Abstract:

BACKGROUND:The potential of the D-isomerization of 4-borono-2-18F-fluoro-phenylalanine (18F-FBPA) to improve its target tumor to non-target normal brain tissue ratio (TBR) was evaluated in rat brain glioma and compared with those of L- and D-11C-methyl-tyrosine (11C-CMT). The L- or D-isomer of 18F-FBPA was injected into rats through the tail vein, and their whole body kinetics and distributions were assessed using the tissue dissection method up to 90 min after the injection. The kinetics of L- and D-18F-FBPA or L- and D-11C-CMT in the C-6 glioma-inoculated rat brain were measured for 90 or 60 min, respectively, using high-resolution animal PET, and their TBRs were assessed. RESULTS:Tissue dissection analyses showed that D-18F-FBPA uptake was significantly lower than that of L-18F-FBPA in the brain and abdominal organs, except for the kidney and bladder, reflecting the faster elimination rate of D-18F-FBPA than L-18F-FBPA from the blood to the urinary tract. PET imaging using 18F-FBPA revealed that although the brain uptake of D-18F-FBPA was significantly lower than that of L-18F-FBPA, the TBR of the D-isomer improved to 6.93 from 1.45 for the L-isomer. Similar results were obtained with PET imaging using 11C-CMT with a smaller improvement in TBR to 1.75 for D-11C-CMT from 1.33 for L-11C-CMT. CONCLUSIONS:The present results indicate that D-18F-FBPA is a better brain tumor imaging agent with higher TBR than its original L-isomer and previously reported tyrosine-based PET imaging agents. This improved TBR of D-18F-FBPA without any pre-treatments, such as tentative blood-brain barrier disruption using hyperosmotic agents or sonication, suggests that the D-isomerization of BPA results in the more selective accumulation of 10B in tumor cells that is more effective and less toxic than conventional L-BPA.

journal_name

EJNMMI Res

journal_title

EJNMMI research

authors

Kanazawa M,Nishiyama S,Hashimoto F,Kakiuchi T,Tsukada H

doi

10.1186/s13550-018-0404-6

subject

Has Abstract

pub_date

2018-06-13 00:00:00

pages

47

issue

1

issn

2191-219X

pii

10.1186/s13550-018-0404-6

journal_volume

8

pub_type

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