Establishing Radiolanthanum Chemistry for Targeted Nuclear Medicine Applications

Abstract

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 better 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.

Keywords: imaging; lanthanum; positron emission tomography; radiochemistry; radiopharmaceuticals.

Figure 1.

Chemical structures of chelators investigated in this work.

Figure 2.. (

A) Region of interest (ROI) analysis of PET images obtained at 1 and 4 h post injection, expressed in percent injected dose per cubic centimeter (% ID/cc). (B) Biodistribution analysis obtained at 4 h post injection, expressed in percent injected dose per gram (% ID/g). These data indicate that ROI analysis provides reliably quantitative information on distribution in organs of interest.

Figure 3.

A maximum intensity projection (MIP) image is provided of static PET/CT images of PC3-PiP/Flu tumor-bearing mice 1h after injection of (A) ^132/135La(macropa)-DUPA and (B) ^132/135La(DO2Apic)-DUPA.