Conjugates of vitamin B12 with Nε-functionalized histidine for labeling with [99mTc(OH2)3(CO)3]+: synthesis and biodistribution studies in tumor bearing mice

In this work, histidine derivatives bearing an acetic acid or a propyl amine substituent on the Nε-atom are conjugated to the b-acid, c-acid and d-acid moiety of cyanocobalamin (vitamin B12) via amide formation. Four different derivatives were prepared with different sites of conjugation (b-, c- or d-acid) and different spacer lengths between histidine and the acid moiety. These conjugates can be efficiently labeled with [99mTc(OH2)3(CO)3]+ at yields higher than 95% under mild conditions (50 °C, 30 min, 10−4 M). The biodistribution of the 99mTc(CO)3 labeled conjugates is determined in mice bearing B16-F10 melanoma tumors. The organ distribution varies significantly for each of the derivatives with the percentage injected dose per gram of tumor tissue ranging from 4.4 ± 0.9 to 9.2 ± 2.0.