title: High resolution SPECT imaging for visualization of intratumoral heterogeneity using a SPECT/CT scanner dedicated for small animal imaging.
abstract: OBJECTIVE
  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 (111)In 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 (111)In met this requirement and were administered to tumor-bearing mice. SPECT imaging successfully showed heterogeneous (111)In 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.
  
  
  CONCLUSIONS
  Intratumoral heterogeneity was successfully visualized under the optimized conditions using a SPECT/CT scanner.
authors: Functional Imaging Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwanoha, Kashiwa, Chiba, Japan. ioumeda@east.ncc.go.jp
authors: Izumi O
authors: IO
authors: Umeda
authors: Kotaro
authors: K
authors: Tani
authors: Keisuke
authors: K
authors: Tsuda
authors: Masamitsu
authors: M
authors: Kobayashi
authors: Mayumi
authors: M
authors: Ogata
authors: Sadaaki
authors: S
authors: Kimura
authors: Mitsuyoshi
authors: M
authors: Yoshimoto
authors: Shuji
authors: S
authors: Kojima
authors: Kunikazu
authors: K
authors: Moribe
authors: Keiji
authors: K
authors: Yamamoto
authors: Noriyuki
authors: N
authors: Moriyama
authors: Hirofumi
authors: H
authors: Fujii
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D064847:Multimodal Imaging / Q000295:instrumentation / Q000379:methods*; D019047:Phantoms, Imaging; D049268:Positron-Emission Tomography; D012513:Sarcoma, Experimental / Q000000981:diagnostic imaging* / Q000473:pathology*; D013997:Time Factors; D014057:Tomography, X-Ray Computed