Preclinical Characterization of 86/90 Y-NM600 in a variety of murine and human cancer tumor models.

We characterize the in vivo biodistribution and tumor selectivity of 86 Y-NM600, a theranostic alkylphosphocholine radiometal chelate with broad tumor selectivity, in a variety of preclinical cancer models. Methods: Mice bearing flank tumors (representative of lung, pancreatic, prostate, liver, skin, and lymphoid cancers) were injected intravenously (IV) with 9.25 MBq of 86 Y-NM600 and imaged longitudinally over 4-5 days using microPET/CT. Percent injected activity per gram (%IA/g) for each volume-of-interest (VOI) was measured at each time point for the organs of interest. Mice were euthanized after the final time point and the tumor and organs of interest were counted with an automatic gamma counter. Absorbed doses delivered by 90 Y-NM600 per injected activity (Gy/MBq) were estimated. Mice bearing B78 flank tumors were injected with a prescription of 90 Y-NM600 that delivered 2.5 Gy of absorbed tumor dose and was compared to an equivalent absorbed dose delivered via external beam radiotherapy (XRT) using tumor volume as a measure of response. Histology and complete blood counts (CBC) were analyzed in naïve C57BL/6 mice who were injected with 9.25 MBq of 90 Y-NM600 at 5, 10, and 28 days post injection (p.i.). Results: PET imaging showed consistent tumor accumulation and retention across all tumor models investigated with little off-target retention of NM600 except for in the liver, which is characteristic of hepatobiliary metabolism. The tumor uptake was highest in the pancreatic and lymphoid cancer models, reaching peak concentrations of 9.34 ± 2.66%IA/g ( n = 3) and 9.10 ± 0.13 %IA/g ( n = 3), respectively, at approximately 40-48 hr post injection. These corresponded to tumor dose estimates of 2.72 ± 0.33 Gy/MBq and 2.67 ± 0.32 Gy/MBq, respectively. In the toxicity study, there were no visible signs of acute toxicity by histology, and perturbation of hematological parameters was transient when observed, returning to pre-therapy levels after 28 days. Conclusion: NM600 is a theranostic agent with a unique ability to selectively target a variety of cancer types, presenting a unique opportunity for PET image guided TRT and combination with immunotherapies.