The [alpha]-Camera: A Quantitative Digital Autoradiography Technique Using a Charge-Coupled Device for Ex Vivo High-Resolution Bioimaging of [alpha]-Particles

摘要

Bioconjugates used in internal radiotherapy exhibit heterogeneous distributions in organs and tumors, implying a risk of nonuniform dose distribution in therapeutic applications using α-particle emitters. Tools are required that provide data on the activity distribution for estimation of absorbed dose on a suborgan level. The α-camera is a quantitative imaging technique developed to detect α-particles in tissues ex vivo. The aim of this study was to evaluate the characteristics of this imaging system and to exemplify its potential use in the development of α-radioimmunotherapy. Methods: The α-camera combines autoradiography with a scintillating technique and optical registration by a charge-coupled device (CCD). The imaging system characteristics were evaluated by measurements of linearity, uniformity, and spatial resolution. The technique was applied for quantitative imaging of ^sup 211^At activity distribution in cryosections of tumors, kidney, and whole body. Intratumoral activity distributions of tumor-specific ^sup 211^At-MX35-F(ab')^sub 2^ were studied at various times after injection. The postinjection activity distributions in the renal cortex and whole kidneys were compared for ^sup 211^At-F(ab')^sub 2^ and ^sup 211^At-IgG trastuzumab. Results: Quantitative analysis of α-camera images demonstrated that the pixel intensity increased linearly with activity in the imaged specimen. The spatial resolution was 35 ± 11 μm (mean ± SD) and the uniformity better than 2%. Kidney cryosections revealed a higher cortex-to-whole kidney ratio for ^sup 211^At-F(ab')^sub 2^ than for ^sup 211^At-IgG (1.38 ± 0.03 and 0.77 ± 0.04, respectively) at 2 h after injection. Nonuniform intratumoral activity distributions were found for tumor-specific ^sup 211^At-MX35-F(ab')^sub 2^ at 10 min and 7 h after injection; after 21 h, the distribution was more uniform. Conclusion: The characteristics of the α-camera are promising, suggesting that this bioimaging system can assist the deveiopment, evaluation, and refinement of future targeted radiotherapy approaches using α-emitters. The α-camera provides quantitative data on the activity distribution in tissues on a near-cellular scale and can therefore be used for small-scale dosimetry, improving the prediction of biologic outcomes with a-particles with short path length and high linear energy transfer. [PUBLICATION ABSTRACT] Show less