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

Abstract Introduction The aim of this study was to assess the use of 201 thallium 3+ ( 201 Tl 3+ ) 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 201 Tl 3+ were investigated, and the levels of stability of these chelates were tested in vitro and in vivo. Methods 201 Tl(I)Cl was treated with hydrochloric acid and ozone to form 201 Tl(III)Cl 3 . The procedure for labeling of DOTA and DTPA was optimized, testing different buffer solutions and pH values. The stability levels of 201 Tl(III)–DOTA and 201 Tl(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 201 Tl(III)–DOTA were performed, comparing the biodistribution of 201 Tl(III)–DOTA with that of 201 Tl(I)Cl in a single-isotope study and with that of 177 Lu(III)–DOTA in a dual-isotope single photon emission computed tomography study. Results 201 Tl(III)–DTPA, 201 Tl(III)–DOTA and 177 Lu(III)–DOTA were prepared with >95% radiochemical purity. While 201 Tl(III)–DOTA showed a prolonged level of stability in buffer and serum, 201 Tl was quickly released from DTPA in serum. Apart from some urinary excretion, the biodistribution of DOTA-chelated 201 Tl 3+ was similar to that of free (ionic) 201 Tl + and did not match the biodistribution of 177 Lu(III)–DOTA. This indicated a limited stability of 201 Tl(III)–DOTA complexes in vivo. Conclusion Despite promising results on the labeling and in vitro stability of 201 Tl(III)–DOTA, our in vivo results indicate that the integrity of 201 Tl(III)–DOTA decreases to 201 Tl 3+ as a radiolabel for tracer imaging.