Date: 12 Oct 2011
High resolution SPECT imaging for visualization of intratumoral heterogeneity using a SPECT/CT scanner dedicated for small animal imaging
Tumor interiors are never homogeneous and in vivo visualization of intratumoral heterogeneity would be an innovation that contributes to improved cancer therapy. But, conventional nuclear medicine tests have failed to visualize heterogeneity in vivo because of limited spatial resolution. Recently developed single photon emission computed tomographic (SPECT) scanners dedicated for small animal imaging are of interest due to their excellent spatial resolution of <1 mm, but few studies have focused on the evaluation of intratumoral heterogeneity. We investigated the optimal conditions related to high resolution imaging of heterogeneous tumor interiors using a small animal SPECT scanner.
The conditions related to SPECT/CT visualization of heterogeneous tumor interiors were investigated using phantoms with 111In and simulations of actual small animal imaging. The optimal conditions obtained were validated by in vivo imaging of sarcoma 180-bearing mice.
Larger number of counts must be obtained within limited acquisition time to visualize tumor heterogeneity in vivo in animal imaging, compared to cases that simply detect tumors. At an acquisition time of 30 min, better image quality was obtained with pinhole apertures diameter of 1.4 mm than of 1.0 mm. The obtained best spatial resolution was 1.3 mm, it was acceptable for our purpose, though a little worse than the best possible performance of the scanner (1.0 mm). Additionally, the reconstruction parameters, such as noise suppression, voxel size, and iteration/subset number, needed to be optimized under the limited conditions and were different from those found under the ideal condition. The minimal radioactivity concentration for visualization of heterogeneous tumor interiors was estimated to be as high as 0.2–0.5 MBq/mL. Liposomes containing 111In met this requirement and were administered to tumor-bearing mice. SPECT imaging successfully showed heterogeneous 111In distribution within the tumors in vivo with good spatial resolution. A threshold of 0.2 MBq/g for clear visualization of tumor heterogeneity was validated. Autoradiograms obtained ex vivo of excised tumors confirmed that the in vivo SPECT images accurately depicted the heterogeneous intratumoral accumulation of liposomes.
Intratumoral heterogeneity was successfully visualized under the optimized conditions using a SPECT/CT scanner.
Beekman FJ, van der Have F, Vastenhouw B, van der Linden AJ, van Rijk PP, Burbach JP, et al. U-SPECT-I: a novel system for submillimeter-resolution tomography with radiolabeled molecules in mice. J Nucl Med. 2005;46(7):1194–200.PubMed
Ogihara-Umeda I, Sasaki T, Kojima S, Nishigori H. Optimal radiolabeled liposomes for tumor imaging. J Nucl Med. 1996;37(2):326–32.PubMed
Ogihara-Umeda I, Nishigori H. Radiolabeled liposomes for diagnostic imaging. In: Arshady R, editor. Radiolabeled and magnetic particulates in medicine and biology. London: Citus; 2001. p. 123–48.
Ogihara-Umeda I, Kojima S. Increased delivery of gallium-67 to tumors using serum-stable liposomes. J Nucl Med. 1988;29(4):516–23.PubMed
Ogihara-Umeda I, Sasaki T, Nishigori H. Development of a liposome-encapsulated radionuclide with preferential tumor accumulation—the choice of radionuclide and chelating ligand. Int J Radiat Appl Instrum B. 1992;19(7):753–7.CrossRef
Zhao S, Kuge Y, Mochizuki T, Takahashi T, Nakada K, Sato M, et al. Biologic correlates of intratumoral heterogeneity in 18F-FDG distribution with regional expression of glucose transporters and hexokinase-II in experimental tumor. J Nucl Med. 2005;46(4):675–82.PubMed
Busk M, Horsman MR, Jakobsen S, Keiding S, van der Kogel AJ, Bussink J, et al. Imaging hypoxia in xenografted and murine tumors with 18F-fluoroazomycin arabinoside: a comparative study involving microPET, autoradiography, pO2-polarography, and fluorescence microscopy. Int J Radiat Oncol Biol Phys. 2008;70(4):1202–12.PubMedCrossRef
Ueda M, KudoT, Mutou Y, Umeda IO, Miyano A, Ogawa K, et al. Evaluation of [125I]IPOS as a molecular imaging probe for hypoxia-inducible factor-1-active regions in a tumor: comparison among SPECT/CT imaging, autoradiography, and immunohistochemistry. Cancer Sci. 2011. doi:10.1111/j.1349-7006.2011.02057.x.
- High resolution SPECT imaging for visualization of intratumoral heterogeneity using a SPECT/CT scanner dedicated for small animal imaging
Annals of Nuclear Medicine
Volume 26, Issue 1 , pp 67-76
- Cover Date
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- Small animal
- Tumor heterogeneity
- Industry Sectors
- Author Affiliations
- 1. Functional Imaging Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan
- 2. Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan
- 4. Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan
- 3. Division of Cancer Development System, National Cancer Center Research Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
- 5. Research Center for Cancer Prevention and Screening, National Cancer Center, 1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan