This review summarizes the applications of iodonium compounds in the rapidly developing field of Positron Emission Tomography (PET). Reactions of diaryliodonium salts with fluoride anion have found wide practical application in PET as a fast and convenient method for the introduction of the radioactive [18 F]-fluoride into radiotracer molecules. The best synthetic methods for the preparation of iodonium precursors for PET are described, the mechanistic aspects of nucleophilic fluorination reaction are discussed, and specific examples of the preparation of PET radioligands are provided.

Non-invasive radionuclide imaging of human epidermal growth factor receptor type 2 (HER2) expression in breast, gastroesophageal, and ovarian cancers may stratify patients for treatment using HER2-targeted therapeutics. Designed ankyrin repeat proteins (DARPins) are a promising type of targeting probe for radionuclide imaging. In clinical studies, the DARPin [99mTc]Tc-(HE)3-G3 labeled using a peptide-based chelator His-Glu-His-Glu-His-Glu ((HE)3), provided clear imaging of HER2 expressing breast cancer 2–4 h after injection. The goal of this study was to evaluate if the use of cysteine-containing peptide-based chelators Glu-Glu-Glu-Cys (E3C), Gly-Gly-Gly-Cys (G3C), and Gly-Gly-Gly-Ser-Cys connected via a (Gly-Gly-Gly-Ser)3-linker (designated as G3-(G3S)3C) would further improve the contrast of imaging using 99mTc-labeled derivatives of G3. The labeling of the new variants of G3 provided a radiochemical yield of over 95%. Labeled G3 variants bound specifically to human HER2-expressing cancer cell lines with affinities in the range of 1.9–5 nM. Biodistribution of [99mTc]Tc-G3-G3C, [99mTc]Tc-G3-(G3S)3C, and [99mTc]Tc-G3-E3C in mice was compared with the biodistribution of [99mTc]Tc-(HE)3-G3. It was found that the novel variants provide specific accumulation in HER2-expressing human xenografts and enable discrimination between tumors with high and low HER2 expression. However, [99mTc]Tc-(HE)3-G3 provided better contrast between tumors and the most frequent metastatic sites of HER2-expressing cancers and is therefore more suitable for clinical applications.

радиохимического соединения на основе меченых 99mТс рекомбинантных адресных молекул для визуализации клеток с гиперýкспрессией Her-2/neu.

В настоящее время проводятся доклинические исследования нового производного октреотида с хелатный центром (DPAH-октреотид) для связывания 99mTc, для радионуклидной диагностики нейроэндокринных опухолей. Способ получения DPAH-октреотида основан на реакции образования амидной связи между амино-группой остатка D-фенилаланина и бифункциональным хелатирующим агентом сукцинимид-1-ил 6-(бис(пиридин-2-илметил)амино)гексаноатом. Для обеспечения качества DPAH-октреотида предложена ВЭЖХ методика для определения подлинности, посторонних примесей и количественного содержания. При проведении валидации установлено, что по параметрам — специфичность, предел обнаружения, линейность, правильность, сходимость и внутрилабораторная прецизионность аналитическая методика ВЭЖХ определения показателей качества DPAH-октреотида соответствует требованиям, предъявляемым к методикам, и может использоваться для контроля качества готовой продукции при производстве реагента для приготовления радиофармацевтического препарата на его основе.

[18F]Fluoroaliphatic carboxylic acids are important PET tracers that have demonstrated a considerable potential to address the fatty acid oxidation‐dependent processes in clinical patients. Herein, we report an efficient radiosynthetic approach to ω‐[18F]fluoroaliphatic carboxylic esters and acids by nucleophilic radiofluorination of the readily available iodocarboxylic esters. Methyl 6‐[18F]fluorohexanoate was further applied as a starting material for the preparation of the succinimide ester (NHS ester)‐containing bifunctional radiofluorinated prosthetic group in two simple steps, 10 min each. The synthesized NHS ester of 6‐[18F]fluorohexanoic acid can serve as an important reagent for a quick and efficient conjugation with peptides or proteins via amino groups of lysines.

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