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Actinium-225 Labeled Antibody Therapy Micro-Scale Dosimetry in a Murine Model and Predicted Dosimetric Impact for Human Clinical Use

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R Hobbs

A Josefsson1 , J Nedrow1 , S Park1 , F Bruchertseifer2 , A Morgenstern2 , G Sgouros1 , RF Hobbs7*, (1) Johns Hopkins University, Baltimore, Maryland, (2) Institute for TransUranium Elements, Karlsruhe, Germany


SU-I-GPD-T-661 (Sunday, July 30, 2017) 3:00 PM - 6:00 PM Room: Exhibit Hall

Purpose: Alpha-particle emitting radionuclides have high potential for metastasized disease therapy. Renal toxicity is limiting in many pre-clinical experiments. The dosimetry has been well qualitatively characterized using the macro-to-micro (M2M) small scale methodology. Here we examine how the tumor burden affects the absorbed dose to the kidneys from both the ²²⁵Ac labeled antibody and the free daughter ²¹³Bi in a transgenic immunocompetent mouse model applying M2M and extrapolating to human use.

Methods: neu-N mice were injected subcutaneously with NT2.5 cells four weeks prior to activity. Healthy as well as tumor bearing mice were injected intravenously with 37 kBq of ²²⁵Ac-7.16.4 and sacrificed at 5 different time points after injection. Kidneys were harvested and continuously counted over 4.5 hours. A double exponential expression was fit to the data to obtain the activity of ²²⁵Ac-7.16.4 and free ²¹³Bi per unit mass within the kidneys at sacrifice. Whole organ kidney dosimetry for ²²⁵Ac-7.16.4 and free ²¹³Bi was determined using this measured biodistribution data, while micro-scale localization was previously obtained.

Results: The absorbed dose to the kidneys for tumor bearing mice from ²²⁵Ac-7.16.4 was 73.7 mGy/kBq and 131 mGy/kBq from free ¹³Bi. For the non-tumor bearing mice the corresponding absorbed dose to the kidneys was 19.3 mGy/kBq and 41.8 mGy/kBq, respectively. Translating to human from the mouse model using a range expected tumor burdens shows a lesser dosimetric impact in humans due to the lower tumor/kidney mass ratio.

Conclusion: Tumor bearing mice have a higher kidney absorbed dose compared with the non-tumor bearing mice, due to less free ²¹³Bi from decaying ²²⁵Ac-7.16.4 in the tumor. Free ²¹³Bi contribution to kidney dose is expected to be less in humans where the tumor burden to kidney mass ratio is much lower than in the murine model.

Funding Support, Disclosures, and Conflict of Interest: Funding support from the NIH/NCI R01 CA157542 (Hobbs), NIH/NCI 2R01 CA116477 (Sgouros), Ac-225 provided free of charge by ITU.

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