Synthesis and preliminary radiopharmacological characterisation of an ¹¹C‐labelled azadipeptide nitrile as potential PET tracer for imaging of cysteine cathepsins

Abstract

An O-methyltyrosine-containing azadipeptide nitrile was synthesised and investigated for its inhibitory activity towards cathepsins L, S, K, and B. Labelling with carbon-11 was accomplished by reaction of the corresponding phenolic precursor with [ 11 C]methyl iodide starting from cyclotron-produced [ 11 C]methane. Radiopharmacological evaluation of the resulting radiotracer in a mouse xenograft model derived from a mammary tumour cell line by small animal PET imaging indicates tumour targeting with complex pharmacokinetics. Radiotracer uptake in the tumour region was considerably lower under treatment with the nonradioactive reference compound and the epoxidebased irreversible cysteine cathepsin inhibitor E64. The in vivo behaviour observed for this radiotracer largely confirms that of the corresponding 18 Ffluoroethylated analogue and suggests the limited suitability of azadipeptide nitriles for the imaging of tumour-associated cysteine cathepsins despite targetmediated uptake is evidenced.

Azanitrile Inhibitors of the SmCB1 Protease Target Are Lethal to Schistosoma mansoni: Structural and Mechanistic Insights into Chemotype Reactivity

“…Except for compound 3c , the inhibitors used in this study have been synthesized as described. − , Thin-layer chromatography was carried out on Merck (Darmstadt, Germany) aluminum sheets, silica gel 60 F254. Detection was performed with a UV light at 254 nm.…”

Active Targeting of Dendritic Polyglycerols for Diagnostic Cancer Imaging

“…ROI time activity curves were derived for subsequent data analysis. Data were calculated as standardized uptake value (SUV = activity concentration in tissue [Bq g −1 ] × body weight [g]/injected dose [Bq]), defined as the tracer concentration at a certain time point normalized to injected dose per unit body weight …”

Radiolabeled Silicon-Rhodamines as Bimodal PET/SPECT-NIR Imaging Agents

“…In Figure 3 the HPLC chromatograms of the purified radioactive SiRs After HPLC purification, solid phase extraction for solvent exchange and formulation in ethanol, [ 18 F]10a and [ 18 F]10b were further characterized by determination of the partition coefficient using the conventional shake-flask method [81,82]. The experimentally determined value for [ 18 F]10a was log D pH=7.4 = 2.92 ± 0.32 whereas [ 18 F]10b shows a slightly enhanced lipophilic character with log D pH=7.4 = 3.22 ± 0.18.…”