Establishing Radiolanthanum Chemistry for Targeted Nuclear Medicine Applications

We report the first targeted nuclear medicine application of the lanthanum radionuclides (132/135)La. These isotopes represent a matched pair for diagnosis via the positron emissions of (132)La and therapy mediated by the Auger electron emissions of (135)La. We identify two effective chelators, known as DO3Apic and macropa, for these radionuclides. The 18-membered macrocycle, macropa, bound (132/135)La with superior molar activity than DO3Apic under similar conditions. These chelators were conjugated to the prostate-specific membrane antigen (PSMA)-targeting agent DUPA to assess the use of radiolanthanum for in vivo imaging. The (132/135)La-labeled targeted constructs showed high uptake in tumor xenografts expressing PSMA. This study validates the use of these radioactive lanthanum isotopes for imaging applications and motivates future work to assess the therapeutic effects of the Auger electron emissions of (135)La.