Fluorine-18 labeled insulin: a prosthetic group methodology for incorporation of a positron emitter into peptides and proteins

Abstract

In the present study we synthesize 18F-labeled insulin of high specific radioactivity. A new prosthetic group methodology, in which [18F]fluoride displaces a bromide group of 4-(bromomethyl)-benzoylamine intermediates, was used. The 4-(fluoromethyl)benzoyl product was chemically stable. 18F-Labeled insulin retains the essential biological properties of native insulin, as measured in vitro by binding to insulin receptors on human cells and stimulation of glucose metabolism in rat adipocytes. The overall process can be carried out speedily to yield a product of sufficient purity to permit in vivo studies. The method appears to be applicable to a wide variety of peptides.

Agonist derived molecular probes for A2 adenosine receptors

“…A prosthetic group for radiofluorination of functionalized drugs and peptides was recently reported (Shai et al, 1989). This group consisted of a 4-fluoromethylbenzoyl moiety (FMB) obtained through nucleophilic fluorination (with 18 F) of the corresponding 4-bromomethylbenzoyl derivatives.…”

“…As a potential "F probe for in vivo positron emission tomography (PET) of A 2A adenosine receptors, an FMB derivative of CGS21680, compound 16, in which the spacer chain consists of 1,4-diaminobutane, was prepared. It was synthesized by condensing the 4-(4-fluoromethyl)benzoylamino)-butaneamino (Shai et al, 1989) with CGS21680.…”

Preparation of no‐carrier‐added [124I]A14‐iodoinsulin as a radiotracer for positron emission tomography

“…Insulin has also been labelled with the positron-emitter, fluorine-18 (t 1/2 =109.7 min), via a prosthetic group. 16 This procedure is however complex and low yielding.…”

Synthesis of 4-([18F]fluoromethyl)-2-chlorophenylisothiocyanate: A novel bifunctional 18F-labelling agent

“…This approach comprises [ 18 F]fluoride incorporation into small organic molecules capable of being linked to peptides, proteins, oligonucleotides and antibodies under mild conditions. Such linkage of 18 F-labelled prosthetic groups can be accomplished via acylation [8][9][10][11][12], amidation [13], imidation [7], alkylation [7], photochemical conjugation [12] and solid-phase synthesis [14]. Every method has its own advantages and limitations.…”

“…In a series of reports Lang and Eckelman [10,15], Shai et al [13] and Hedberg and Långström [16] utilized several 18 F-labelled benzylfluoride derivatives as prosthetic groups which could be synthesized in moderate radiochemical yields in a one-step procedure. However, the single-step preparation advantage is jeopardised by the low stability of 18 F-labelled benzylfluorides in terms of a rapid in vivo radiodefluorination, resulting in non-desired high bone accumulation.…”