Molecular Imaging of Hypoxia: Strategies for Probe Design and Application

Abstract

Tumor hypoxia is a negative prognostic factor and its precise imaging is of great relevance to therapy planning. The present review summarizes various strategies of probe design for imaging hypoxia with a variety of techniques such as PET, SPECT and fluorescence imaging. Synthesis of some important probes that are used for preclinical and clinical imaging and their mechanism of binding in hypoxia are also discussed.

Fig. (1)

Mechanism of intracellular retention of nitroimidazole-containing molecules.

Fig. (2)

Nitroimidazole-containing hypoxia probes.

Fig. (3)

Cu-ATSM, its derivatives and proposed mechanism of action.

Fig. (4)

[^99mTc]-HL91, a non-nitroimidazole hypoxia SPECT radiotracer.

Fig. (5)

Relation between hypoxia and CA IX.

Fig. (6)

A fluorescent CA IX probe.

Scheme 1

Synthesis of [¹⁸F]-FMISO.

Scheme 2

Synthesis of [¹⁸F]-FMISO.

Scheme 3

Synthesis of NITTP, a precursor for [¹⁸F]-FMISO.

Scheme 4

Synthesis of [¹⁸F]-FMISO from NITTP.

Scheme 5

Synthesis of ¹⁸F-FAZA.

Scheme 6

Attempt of synthesis of ¹⁸F-EF5 using ¹⁸F⁻.

Scheme 7

Synthesis of [¹⁸F]-EF5 using ¹⁸F₂.

Scheme 8

Mechanism of a coumarin based fluorescent hypoxia agent.

Scheme 9

A pH sensitive hypoxia probe.

Scheme 10

Radiolabelling of [¹⁸F]-TFSB.