Determination of kidney dose distributions using autoradiography and HpGe spectroscopy of kidney after injection of 225Ac-HuM195

Objectives A major concern of using 225AcHuM195 is renal toxicity from the 3 α-emitting daughters released from the decay of 225Ac. We determined the dose distribution of 225Ac and its daughters in kidney after administration 225AcHuM195 antibody.

Methods Mice injected with 600 nCi of 225AcHuM195 antibody were sacrificed at 24,96,and 144hr.The kidneys were removed immediately. Ten sections were collected from one kidney from each animal and imaged by digital autoradiography(DAG). Exposures (EXP) were performed immediately after the sectioning (EXP 1hr), and 24hr after sectioning (EXP 16-30hr). The 1st image shows total activity distribution mainly from the daughters that translocate there. By the start of 2nd EXP all daughters had decayed,and the 225Ac parent was in equilibrium with the newly generated daughters,which remained at the parent's location. A HpGe detector was used to resolve 225Ac activity contribution from that of its daughters by measuring emitted γ's (218 & 440keV) in the second kidney.Known activity standards were measured by DAG and spectroscopy.

Results DAG images and spectra from the HpGe were calibrated with the respective standards.The dose to the cortex was calculated using the DAG as 27.3Gy from 225Ac and 4.6Gy from 213Bi and for the medulla were 17Gy (225Ac) and 6.5Gy (213Bi). The WK doses from the spectroscopy were determined to be 17.4Gy (225Ac) and 8.7Gy (213Bi).

Conclusions Doses from 225AcHUM195 and its daughters were estimated for different regions of the kidney and found to be highly tissue-dependent, and not easily determined from average dose calculations over the kidney as a whole.