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Radiolabelling and evaluation of a novel sulfoxide as a PET imaging agent for tumor hypoxia.

Abstract：

:[¹⁸F]FMISO is the most widely validated PET radiotracer for imaging hypoxic tissue. However, as a result of the pharmacokinetics of [¹⁸F]FMISO a 2h wait between tracer administration and patient scanning is required for optimal image acquisition. In order to develop hypoxia imaging agents with faster kinetics, we have synthesised and evaluated several F-18 labelled anilino sulfoxides. In this manuscript we report on the synthesis, in vitro and in vivo evaluation of a novel fluoroethyltriazolyl propargyl anilino sulfoxide. The radiolabelling of the novel tracer was achieved via 2-[¹⁸F]fluoroethyl azide click chemistry. Radiochemical yields were 23 ± 4% based on 2-[¹⁸F]fluoroethyl azide and 7 ± 2% based on K[¹⁸F]F. The radiotracer did not undergo metabolism or defluorination in an in vitro assay using S9 liver fractions. Imaging studies using SK-RC-52 tumors in BALB/c nude mice have indicated that the tracer may have a higher pO₂ threshold than [¹⁸F]FMISO for uptake in hypoxic tumors. Although clearance from muscle was faster than [¹⁸F]FMISO, uptake in hypoxic tumors was slower. The average tumor to muscle ratio at 2h post injection in large, hypoxic tumors with a volume greater than 686 mm³ was 1.7, which was similar to the observed ratio of 1.75 for [¹⁸F]FMISO. Although the new tracer showed improved pharmacokinetics when compared with the previously synthesised sulfoxides, further modifications to the chemical structure need to be made in order to offer significant in vivo imaging advantages over [¹⁸F]FMISO.

journal_name

Nucl Med Biol

journal_title

Nuclear medicine and biology

authors

Laurens E,Yeoh SD,Rigopoulos A,Cao D,Cartwright GA,O'Keefe GJ,Tochon-Danguy HJ,White JM,Scott AM,Ackermann U

doi

10.1016/j.nucmedbio.2014.03.001

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

419-25

issue

5

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(14)00060-2

journal_volume

41

pub_type

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