Radiolabelling and evaluation of ^99mTc-Glucaric acid for tumour scintigraphy

Glucaric Acid, a 6-carbon dicarboxylic acid, which behaves invivo somewhat like fructose has been proposed as a potentially useful SPECT imaging agent for acute myocardial infarction that may permit differentiation of necrosis from ischemia. Technetium-labelled sestamibi is FDA approved imaging agent for scintimamography. But breast tumours containing P-glycoprotein which acts as a drug-efflux pump are difficult to image with MIBI because it is rapidly expelled from drug resistant cells. Tc-99m labeled glucarate offers favorable imaging characteristics for detecting drug resistant tumours. Recently it has shown significant accumulation in human breast cancer xenografts in mice. Prompted by these findings we radiolabelled glucaric acid with ^99mTc and evaluated its potential for tumor scintigraphy using Ehrlich Ascitis tumor implanted mice as the experimental model.

Glucaric acid was labeled with technetium using Sncl2 as the reducing agent. All the lebelling parameters such as pH, concⁿ of SnCl₂ were standardized to get maximum labeling yield. The complex was highly stable (>97%) at invitro and in vivo conditions showing only 2–3% detachment of the complex at 24 hr. Protein binding was 72% and lipophilicity were 1.6% respectively. Blood kinetics in rabbits was appreciably fast exhibiting approx. 66% activity washout at 5’ followed by a slow phase after 1 hr. Biodistribution carried out in mice revealed its maximum accumulation in kidneys (8.9% per gm at 1 hr) followed by liver (2.04% per gm at 1 hr). The values declined with time but kidneys were the main route of excretion. Target to non target ratio was obtained in mice by scintigraphy studies. T/NT ratio was 5: 1 at 3 hr, which corroborated with the finding obtained with the biodistribution studies carried out in tumor bearing mice.

The study concludes the substantial potential of ^99mTc-Glucaric acid for tumor scintigraphy. Its binding with breast cancer cell lines and receptor binding studies are in progress for further validitation of the findings.