Synthesis and preliminary evaluation of a 99mTc labelled deoxyglucose complex {[99mTc]DTPA-bis(DG)} as a potential SPECT based probe for tumor imaging

Abstract

Carbohydrate based radiotracers have been in routine use as a potential PET imaging agent for tumor targeting, worldwide. The aim of our study was to develop a cost effective and more accessible SPECT based tumor targeted molecular imaging probe. A 1-D-deoxyglucose conjugate was proposed and evaluated as a tumor imaging agent. DTPA-bis(DG) was synthesized by conjugating two molecules of glucose employing a click chemistry approach. It involved a facile methodology, characterization and subsequent radiolabelling with ^99mTc with high radiochemical purity and specific activity (187 ± 17 MBq μmol⁻¹) followed by in vitro and in vivo evaluation to prove its potency as an imaging agent. In vitro cytotoxicity studies in the A549 and HEK cell lines showed no substantial toxicity. A cell uptake study revealed that the transportation of [^99mTc]DTPA-bis(DG) was GLUT1 independent. In vivo blood kinetic studies in New Zealand rabbits showed fast clearance with a T_d1/2 of 28.12 ± 0.63 min and T_e1/2 = 101.25 ± 0.34. A significant tumor uptake of 3.88 ± 0.05% ID per g was observed in A549 tumor bearing mice at 4 h p.i. The tumor-to-muscle and tumor-to-blood ratios at 4 h p.i. were 20.46 ± 0.07 and 3.59 ± 0.03 respectively. No significant persistence in any other organs was observed. The tumor (A549) grafted in athymic mice was clearly distinguishable in the gamma-scintigraphy image. The results suggested that this [^99mTc]glycoconjugate would be a promising candidate for cancer targeted imaging.