Original Article

Annals of Nuclear Medicine

, Volume 26, Issue 1, pp 67-76

High resolution SPECT imaging for visualization of intratumoral heterogeneity using a SPECT/CT scanner dedicated for small animal imaging

  • Izumi O. UmedaAffiliated withFunctional Imaging Division, Research Center for Innovative Oncology, National Cancer Center Hospital East Email author 
  • , Kotaro TaniAffiliated withFunctional Imaging Division, Research Center for Innovative Oncology, National Cancer Center Hospital East
  • , Keisuke TsudaAffiliated withFunctional Imaging Division, Research Center for Innovative Oncology, National Cancer Center Hospital East
  • , Masamitsu KobayashiAffiliated withFunctional Imaging Division, Research Center for Innovative Oncology, National Cancer Center Hospital EastFaculty of Pharmaceutical Sciences, Tokyo University of Science
  • , Mayumi OgataAffiliated withFunctional Imaging Division, Research Center for Innovative Oncology, National Cancer Center Hospital EastGraduate School of Pharmaceutical Sciences, Chiba University
  • , Sadaaki KimuraAffiliated withFunctional Imaging Division, Research Center for Innovative Oncology, National Cancer Center Hospital East
  • , Mitsuyoshi YoshimotoAffiliated withDivision of Cancer Development System, National Cancer Center Research Center
  • , Shuji KojimaAffiliated withFaculty of Pharmaceutical Sciences, Tokyo University of Science
  • , Kunikazu MoribeAffiliated withGraduate School of Pharmaceutical Sciences, Chiba University
    • , Keiji YamamotoAffiliated withGraduate School of Pharmaceutical Sciences, Chiba University
    • , Noriyuki MoriyamaAffiliated withResearch Center for Cancer Prevention and Screening, National Cancer Center
    • , Hirofumi FujiiAffiliated withFunctional Imaging Division, Research Center for Innovative Oncology, National Cancer Center Hospital East

Abstract

Objectives

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.

Methods

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.

Results

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.

Conclusion

Intratumoral heterogeneity was successfully visualized under the optimized conditions using a SPECT/CT scanner.

Keywords

Small animal SPECT Tumor heterogeneity 111In Liposome