Direct radiolabeling of Folate with Tc-99m using QbD approach: A step closer to folate based diagnostic agent

Abstract

The aim of the presented work was to develop folate based radiolabeled compound intended to be used as diagnostic aid for the various folate-receptor overexpressing cancers eg. breast cancer, brain tumors, lung cancer etc. Folate was directly radiolabeled with Tc-99m using Quality-by-Design and encapsulated in micellar nanocarriers. The authors are of the view that the stable radiolabeled folate could be of potential diagnostic value in cancers overexpressing folate receptors thereby opening novel possibilities to diagnostic applications of radiolabeled folate.

Summary for technical notes

Folic acid was directly radiolabeled with Tc-99m utilizing a quality by design approach. The experimental trials were designed using the Box-Behenken design with the concentration of drug, concentration of reducing agent and the incubation time as dependent variable and percent radiolabeling as the response for the same. The applied design in the method section was validated with a series of experiments and the percent labeling of the FA with Tc-99m was found to be around 94%. The radiolabeled compound was imperilled to stability evaluation by incubating the same with serum and physiological pH and the same was found to be stable at the end of 4h. On subjecting to DTPA challenge test, the compound displayed no change in the radiolabeling percentage thereby indicating the robustness of the formed Tc-99m-FA complex, The radiolabeled Tc-99m-FA was further encapsulated into micellar nanocarriers and the same were also found to be robust and stable.