Abstract
Multimodal bioluminescence (BLI) and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging were investigated as means to monitor somatostatin receptor subtype 2 (SST2)-positive neuroendocrine tumors as both a subcutaneously implanted and a liver metastasis animal model in mice and rats. Ultimately, such a model will be of use for studying SST2-targeted peptide receptor radionuclide therapy (PRRT). CA20948 cells were transfected with a green fluorescent protein/luciferase plasmid construct. Cells were inoculated subcutaneously in the shoulder of nude mice: nontransfected cells in the left shoulder and transfected cells in the right shoulder. BLI, SPECT/CT imaging, biodistribution analysis, and ex vivo autoradiography of the tumors were performed. BLI and SPECT/CT imaging were also performed on an intrahepatic tumor model in the rat. Caliper volume measurement of transfected tumors could be correlated with BLI measurements (R2 = .76). SPECT/CT imaging showed high levels of accumulation of 111In-DTPA-octreotide in control and transfected tumors, which was confirmed by biodistribution analysis and autoradiography. Subcapsular inoculation of transfected cells in rat liver resulted in an intrahepatic tumor, which could be visualized by both SPECT/CT and BLI. Transfection of CA20948 tumor cells did not alter the growth properties of the cell line or the expression of SST2. Transfected tumors could be clearly visualized by BLI and SPECT/CT imaging. The transfected SST2-positive tumor cell line could represent a novel preclinical model for tumor monitoring in studies that aim at further optimizing PRRT for neuroendocrine tumors.
Highlights
Multimodal bioluminescence (BLI) and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging were investigated as means to monitor somatostatin receptor subtype 2 (SST2)-positive neuroendocrine tumors as both a subcutaneously implanted and a liver metastasis animal model in mice and rats
At day 10 after inoculation, the CA20948-luc tumors on the right shoulder were clearly visible by BLI (Figure 5A), whereas the CA20948 tumors inoculated in the left shoulder were not. Both tumors were visualized by SPECT/CT imaging on intravenously injected 111In-DTPA-octreotide, showing comparable levels of uptake and SST2 expression by both the transfected and nontransfected tumors (Figure 5B)
We were able to demonstrate that luciferasetransfected CA20948 pancreatic tumor cells show SST2 expression and 111In-DTPA-octreotide uptake in vivo comparable to that of nontransfected CA20948
Summary
Multimodal bioluminescence (BLI) and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging were investigated as means to monitor somatostatin receptor subtype 2 (SST2)-positive neuroendocrine tumors as both a subcutaneously implanted and a liver metastasis animal model in mice and rats. Such a model will be of use for studying SST2-targeted peptide receptor radionuclide therapy (PRRT). Subcapsular inoculation of transfected cells in rat liver resulted in an intrahepatic tumor, which could be visualized by both SPECT/CT and BLI. To allow for BLI, CA20948 pancreatic tumor cells were stably transfected with a green fluorescent protein (GFP)/luciferase plasmid construct. Tumor models based on these tumor cells in mice and rats were characterized by multimodal BLI and SPECT/CT imaging using 111In-DTPA-octreotide (OctreoScan, Covidien, Petten, the Netherlands)
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