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 alpha-particle emitters. Tools are required that provide data on the activity distribution for estimation of absorbed dose on a suborgan level. The alpha-camera is a quantitative imaging technique developed to detect alpha-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 alpha-radioimmunotherapy. METHODS: The alpha-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 (211)At activity distribution in cryosections of tumors, kidney, and whole body. Intratumoral activity distributions of tumor-specific (211)At-MX35-F(ab')(2) were studied at various times after injection. The postinjection activity distributions in the renal cortex and whole kidneys were compared for (211)At-F(ab')(2) and (211)At-IgG trastuzumab. RESULTS: Quantitative analysis of alpha-camera images demonstrated that the pixel intensity increased linearly with activity in the imaged specimen. The spatial resolution was 35 +/- 11 mum (mean +/- SD) and the uniformity better than 2%. Kidney cryosections revealed a higher cortex-to-whole kidney ratio for (211)At-F(ab')(2) than for (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 (211)At-MX35-F(ab')(2) at 10 min and 7 h after injection; after 21 h, the distribution was more uniform. CONCLUSION: The characteristics of the alpha-camera are promising, suggesting that this bioimaging system can assist the development, evaluation, and refinement of future targeted radiotherapy approaches using alpha-emitters. The alpha-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 alpha-particles with short path length and high linear energy transfer.