Synthesis and in vivo evaluation of 201Tl(III)-DOTA complexes for applications in SPECT imaging

Introduction The aim of this study was to assess the use of 201thallium3+ (201Tl3+) as a radiolabel for nuclear imaging tracers. Methods for labeling of 1,4,7,10-tetraazacyclododecane-N,N',N¿,N'¿ tetraacetic acid (DOTA) and diethylenetriaminepentaacetic acid (DTPA) chelators with 201Tl3+ were investigated, and the levels of stability of these chelates were tested in vitro and in vivo. Methods 201Tl(I)Cl was treated with hydrochloric acid and ozone to form 201Tl(III)Cl3. The procedure for labeling of DOTA and DTPA was optimized, testing different buffer solutions and pH values. The stability levels of 201Tl(III)–DOTA and 201Tl(III)–DTPA were assessed in buffer, mouse serum and human serum (1:1, v/v) at a temperature of 310 K for 48 h. Subsequently, in vivo stability studies with 201Tl(III)–DOTA were performed, comparing the biodistribution of 201Tl(III)–DOTA with that of 201Tl(I)Cl in a single-isotope study and with that of 177Lu(III)–DOTA in a dual-isotope single photon emission computed tomography study. Results 201Tl(III)–DTPA, 201Tl(III)–DOTA and 177Lu(III)–DOTA were prepared with >95% radiochemical purity. While 201Tl(III)–DOTA showed a prolonged level of stability in buffer and serum, 201Tl was quickly released from DTPA in serum. Apart from some urinary excretion, the biodistribution of DOTA-chelated 201Tl3+ was similar to that of free (ionic) 201Tl+ and did not match the biodistribution of 177Lu(III)–DOTA. This indicated a limited stability of 201Tl(III)–DOTA complexes in vivo. Conclusion Despite promising results on the labeling and in vitro stability of 201Tl(III)–DOTA, our in vivo results indicate that the integrity of 201Tl(III)–DOTA decreases to