Diffusing alpha-emitters radiation therapy: In vivo measurements of effective diffusion and clearance rates across multiple tumor types

Background

Diffusing alpha-emitters radiation therapy (“Alpha-DaRT”) is a new modality that uses alpha particles to treat solid tumors. Alpha-DaRT employs interstitial sources loaded with low activities of ${}^{224}\mathrm{Ra}$, designed to release a chain of short-lived alpha-emitters, which diffuse over a few millimeters around each source. Alpha-DaRT dosimetry is described, to first order, by a framework called the “diffusion–leakage” (DL) model.

Purpose

The aim of this work is to estimate the tumor-specific parameters of the DL model from in vivo studies on multiple histological cancer types.

Methods

Autoradiography studies with phosphor imaging were conducted on 113 tumors in mice from 10 cancer cell lines. An observable, referred to as the “effective diffusion length” $L_{eff}$, was extracted from images of histological slices obtained using phosphor screens. The tumor and Alpha-DaRT source activities were measured after excision with a gamma counter to estimate the probability of ${}^{212}\mathrm{Pb}$ clearance from the tumor by the blood, $P_{leak}\left(Pb\right)$.

Results

The measured values of $L_{eff}$ are in the range of 0.2–0.7 mm across different tumor types and sizes. $P_{leak}\left(Pb\right)$ is between 10 and 90% for all measured tumors, and it generally decreases in magnitude and spread for larger tumors.

Conclusions

The measured values of $L_{eff}$ and $P_{leak}\left(Pb\right)$ and associated dose calculations indicate that hexagonal Alpha-DaRT source lattices of $\sim$4-mm spacing with $\mu \mathrm{Ci}$-scale ${}^{224}\mathrm{Ra}$ activities can lead to effective coverage of the tumor volume with therapeutic dose levels, with considerable margin to compensate for local variations in diffusion and leakage.