High specific activity [samarium-153] EDTA for imaging of experimental tumor models

Enriched samarium oxide (98.2% 152Sm2O3) was irradiated in low neutron flux and high neutron flux reactors to produce 153Sm with specific activities of 14.3 GBq and 22.1 TBq mmol-1 Sm, respectively, at the time of use. Formulation of 153Sm as [153Sm]EDTA, with a 1:10 molar ratio of SM:EDTA, provided a stable radiotracer in vitro and in vivo. High specific activity [153Sm]EDTA showed superior uptake in cell culture (20.8 +/- 0.9% vs. 5.5 +/- 0.1% for 6 and 600 pmol Sm per 10(6) cells, respectively) and better tumor index values (51 vs. 37 at 10.9 nmol and 1.09 mumol Sm kg-1, respectively) in the BDF1 mouse/Lewis lung tumor model. High specific activity [153Sm]EDTA scintigrams of Copenhagen x Fisher rats bearing transplanted Dunning R3327 tumors clearly delineated the tumors within 6 hr, with moderate liver and bone uptake and low soft-tissue background. The injected radiotracer underwent rapid central compartment clearance and whole-body elimination. The absence of observed adverse histopathological toxicity combines with high image quality within 6 hr, to support the clinical tumor-imaging potential of this agent. Comparative studies with [67Ga]citrate at molar-equivalent doses indicated that high specific activity [153Sm]EDTA was a superior radiotracer in these in vitro and in vivo models.