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

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

Appropriate collimators in a small animal SPECT scanner with CZT detector

“…On the other hand, PAH was not suitable for SPECT imaging, as it yielded SPECT images with low resolution. Although Mok et al reported that MPH was appropriate for bone scintigraphy using Tc-MDP with about 67 MBq [8], we expected that SPH would be useful with higher radioactivity because the bone scintigraphy was obtained by SPH using 99m Tc-MDP with about 100 MBq [11] and 185…”

“…In current SPECT scanners, cadmium zinc telluride (CZT) semiconductor detectors have been applied to improve energy and spatial resolution [4][5][6][7][8], as compared with sodium iodide (NaI) scintillation detectors, which were used in conventional SPECT scanners [9][10][11][12][13][14][15][16][17][18][19]. Planar and SPECT projection data are acquired using various collimators in clinical settings.…”

Functional Characterization of VEGF- and FGF-induced Tumor Blood Vessel Models in Human Cancer Xenografts

“…Phospholipid concentration was measured using phospholipid assay kit (Wako, Osaka, Japan). 111 In-DTPA encapsulated PEGylated liposomes were generated by following the remote loading method; specifically, the liposomes encapsulating DTPA were labeled with 111 In (Nihon Medi-Physics, Tokyo, Japan) through incubation with 111 In-oxine (34).…”

Radio‐Labeled Nanoparticles for Biomedical Imaging

“…The longer blood circulation time provides enhanced entrapment of LCLs in tumors with improved pharmacokinetics [46][47][48]. A number of liposome probes have been radiolabeled with 99m Tc, 111 In, and 67 ga. pegylated liposomes encapsulated with 111 In-diethylenetriaminepentaacetic acid (DTpA) have been used to target solid tumors [49,50]. Radiolabeling was performed by a transchelation reaction between a lipophilic oxine and hydrophilic DTpA ligands.…”