Radiochemical and radiobiological assessment of a pyridyl-S-cysteine functionalized bombesin derivative labeled with the (99m)Tc(CO)3(+) core

Abstract

Bombesin is a neuropeptide widely studied due to its ability to target various types of cancers. Technetium-99m on the other hand is ideal for diagnostic tumor targeting. The aim of the present study is the investigation of the coupling of the ligand (S)-(2-(2'-pyridyl)ethyl)-d,l-cysteine with the BN-peptide Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met(CONH2) through the spacer aminohexanoic acidand the labeling of the resulting derivative MBN with the synthon [M(CO)3(H2O)3](+) (M=(99m)Tc, Re). The peptide was synthesized according to the SPPS method, purified and characterized by ESI-MS. The new (99m)Tc-labeled biomolecule was stable in vitro, showed high affinity for the human GRP receptor expressed in PC3 cells and the rate of internalization was found to be time-dependent tissue distribution of the radiopeptide was evaluated in normal mice and in prostate cancer experimental models and significant radioactivity uptake was observed in the pancreas of normal mice as well as in PC3 tumors. Dynamic studies of the radiopeptide showed satisfactory tumor images.

Keywords: 1-hydroxybenzotriazole; 9-fluorenylmethyloxycarbonyl; BSA; Boc; Bombesin; Cys; DIC; DIEA; DMEM; DMF; Dulbecco’s modified Eagle medium; EDTA; ESI-MS; EtOH; FBS; Fmoc; HOBt; I.D.; ID; N,N-diisopropylethylamine; PBS; PET; PMSF; PSPMT; ROI; RP/SE-HPLC; RT; Radiolabeling; Radiopharmaceuticals; SCID; SPECT; SPPS; TFA; TIPS; Technetium; Tricarbonyl precursor; bovine serum albumin; cysteine; diisopropylcarbamide; dimethylformamide; electrospray ionization mass spectrometry; ethanol; ethylenediaminetetraacetic acid; fetal bovine serum; injected dose; internal diameter; intravenous; iv; p.i.; phenylmethanesulfonyl fluoride; phosphate buffered saline; position sensitive photomultiplier tube; positron emission tomography; postinjection; regions of interest; reversed-phase/size-exclusion high-performance liquid chromatography; room temperature; severe combined immunodeficiency; single photon emission computerized tomography; solid phase peptide synthesis; t-butyloxycarbonyl; trifluoroacetic acid; triisopropylsilane.