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

Abstract

Bioconjugates used in internal radiotherapy exhibit heterogeneous distributions in organs and tumors, implying a risk of nonuniform dose distribution in therapeutic applications using a-particle emitters. Tools are required that provide data on the activity distribution for estimation of absorbed dose on a suborgan level. The a-camera is a quantitative imaging technique developed to detect a-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 a-radioimmunotherapy. Methods: The a-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(ab9) 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(ab9) 2 and 211 At-IgG trastuzumab. Results: Quantitative analysis of a-camera images demonstrated that the pixel intensity increased linearly with activity in the imaged specimen. The spatial resolution was 35 6 11 mm (mean 6 SD) and the uniformity better than 2%. Kidney cryosections revealed a higher cortex-to-whole kidney ratio for 211 At-F(ab9) 2 than for 211 At-IgG (1.38 6 0.03 and 0.77 6 0.04, respectively) at 2 h after injection. Nonuniform intratumoral activity distributions were found for tumor-specific 211 At-MX35-F(ab9) 2 at 10 min and 7 h after injection; after 21 h, the distribution was more uniform. Conclusion: The characteristics of the a-camera are promising, suggesting that this bioimaging system can assist the development, evaluation, and refinement of future targeted radiotherapy approaches using a-emitters. The a-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. Promi sing results from preclinical studies (1-6) and pilot clinical trials (7,8) have increased the interest in clinical applications using a-emitting radionuclides for the treatment of cancer. The high linear energy transfer (LET) of a-particles yields a potent method of killing cancer cells. The short path length of a-particles in tissues (50-70 mm) is an advantage if the bioconjugate can be targeted specifically to tumor cells. In combination, the high LET and the short path length can make a-particle therapy an effective treatment of micrometastases and small tumors.Because of the short range of a-particles and the heterogeneous distributions of the targeting molecules, the resulting dose distributions within organs and tumor tissues can...

Anti-CD45 radioimmunotherapy using 211At with bone marrow transplantation prolongs survival in a disseminated murine leukemia model

“…27 Cryosections of spleen and femur from leukemia-bearing mice treated with 211 At-B10-30F11 were imaged with the a-camera technique at various time points after radiolabeled injections. At the 3-hour time point, a-camera imaging revealed that 211 At was distributed throughout the spleen and bone marrow, with some variability that correlates with suborgan architecture.…”

Intraperitoneal Radionuclide Therapy – Clinical and Pre-Clinical Considerations

“…Repeated sampling of peritoneal fluid has also been reported ). In principle, measurements or images of biopsies from organs of interest would be valuable (Bäck et al, 2010), but the increased dosimetric accuracy gained must be weighed against the discomfort such invasive procedures cause the patient. Simple, non-invasive methods using uptake probes can also provide important information on the pharmacokinetics for an individual www.intechopen.com patient.…”

Ex Vivo Activity Quantification in Micrometastases at the Cellular Scale Using the α-Camera Technique

“…The a-camera system consisted of a cooled, high-sensitivity charge-coupled device (SXV-H9; Starlight Xpress Ltd.), coupled to a photographic lens (60 mm f/2.8 Micro-Nikkor; Nikon Corp.) (12). Specimens to be imaged (i.e., tissue sections on a scintillating sheet) were placed on an adjustable stand below the photographic lens.…”

“…The excised biologic samples were snap-frozen and cryosectioned as previously described (12). Ten to 20 pairs of consecutive sections were analyzed for each sample: one section for a-camera imaging and the other section for staining with hematoxylin and eosin (H&E) (in some cases, 3 consecutive sections were analyzed [ Fig.…”

“…Recently, a device based on autoradiography, the a-camera, was developed and evaluated by our group (12). This device provides images of activity distribution (of a-emitters) with good spatial resolution (around 35 mm).…”