Kidney, Blood, and Bone Marrow Dosimetry of 225ac-Hu3F8 Targeted Alpha-Emitter Therapy In a Canine Model
Abstract
Purpose
αRPT is a promising treatment modality that is largely impervious to the mechanisms of resistance associated with chemotherapy, conventional radiotherapy, targeted (pathway-inhibition) therapies, and immunotherapy. Osteosarcoma (OS), which frequently expresses the ganglioside GD2 receptor, can be selectively targeted using the anti-GD2 antibody, hu3F8. In this study, we estimated the absorbed doses to the kidneys, blood, bone marrow, and OS lesions where present in canine patient with spontaneously occurring OS following administration of ~5 MBq of 225Ac-Hu3F8 (A3F8) for osteosarcoma treatment.
Methods
The blood was counted for 221Fr and 213Bi activity at multiple time points after A3F8 administration. The time activity curves were integrated to estimate absorbed doses to blood, assuming local energy deposition. We assumed that the maximum absorbed dose to bone marrow was 36% of blood dose based on prior work. SPECT/CT was performed at three time points, 24 h, 48 h and 72 h post administration with energy windows set for both 221Fr and 213Bi emissions. Here too, the 225Ac and 217At decays were assumed to occur at the same location of the 221Fr. Normal organ activities were integrated either numerically, or with a mono-exponential or hybrid fit using MIRDfit software. The absorbed doses to the normal organs were then obtained assuming local energy deposition.
Results
The estimated kidney effective half-life for 221Fr in the dog was 33 h, while that for 213Bi was 36 h. The estimated absorbed doses to the kidney, blood, and bone marrow were 3.5, 1.5, and 0.54 Gy (or for RBE-adjusted AD using an RBE value of 5: 17.5, 7.5, and 2.7 Gy), respectively.
Conclusion
Our results show that the injection of ~5 MBq of 225Ac-Hu3F8 for osteosarcoma treatment does not exceed the dose limit (23 Gy) of the kidneys but exceeds the bone marrow dose limit (2 Gy).