Synthesis of an ¹⁸F‐labeled cyclin‐dependent kinase‐2 inhibitor

Abstract

The radiosynthesis of N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-4-[18 F]fluoro-benzamide [ 18 F]2 as a potential radiotracer for molecular imaging of cyclin-dependent kinase-2 (CDK-2) expression in vivo by positron emission tomography is described. Two different synthesis routes were envisaged. The first approach followed direct radiofluorination of respective nitro-and trimethylammonium substituted benzamides as labeling precursors with no-carrier-added (n.c.a.

Fluorine-18 labelled building blocks for PET tracer synthesis

“…These characteristics are of less importance for the labelling of small molecules, as these generally are more stable and selectivity is not a big issue because a protective group strategy can be applied easily. For the labelling of small molecules, [ 18 84,93,[322][323][324][325][326][327][328][329][330][331][332][333][334][335][336] The main reason is the fact that at various PET imaging centres, the method to synthesise [ 18 F]SFB is readily available and automated for its use in the labelling of peptides. From a practical point of view, it is thus a small step to also use [ 18 F]SFB for the labelling of small molecules.…”

“…As a building block for the synthesis of low molecular weight PET tracers, [ 18 F]SFB is used solely in the base catalysed acylation of primary amine precursors, as shown in Scheme 117. 84,93,[322][323][324][325][326][327][328][329][331][332][333][334][335][336] The main advantages of labelling amine precursors with [ 18 (Table 2). As a consequence, the precursors are easier to synthesise and no removal of the protecting groups is necessary afterwards.…”

“…a Includes removal of acetyl protecting groups. 84,93,[322][323][324][325][326][327][328][329][331][332][333][334][335][336] , which can be easily introduced in peptides (Scheme 123). 340 The radiochemical yields towards the mixtures of endo and exo bicyclic isoxazolidines 540a-c, as measured by HPLC, were 87% for 540a, 91% for 540b and 91% for 540c.…”

Recent Advances in the Development and Application of Radiolabeled Kinase Inhibitors for PET Imaging

“…Multiple additional serine/threonine kinase inhibitors have been recently radiolabeled. These have been aimed at both previously investigated and novel targets including Rho-kinases, Cdk2, PI3K, mTOR, p38α mitogen-activated protein kinase, PKC and PIM1 (Figure 16) [163,164,165,166,167,168,169,170,171]. However, these reports have only described radiosynthetic work without in vitro or in vivo validations so far.…”