title: Pinhole micro-SPECT/CT for noninvasive monitoring and quantitation of oncolytic virus dispersion and percent infection in solid tumors.
abstract: The purpose of our study was to validate the ability of pinhole micro-single-photon emission computed tomography/computed tomography (SPECT/CT) to: 1) accurately resolve the intratumoral dispersion pattern and 2) quantify the infection percentage in solid tumors of an oncolytic measles virus encoding the human sodium iodide symporter (MV-NIS). Sodium iodide symporter (NIS) RNA level and dispersion pattern were determined in control and MV-NIS-infected BxPC-3 pancreatic tumor cells and mouse xenografts using quantitative, real-time, reverse transcriptase, polymerase chain reaction, autoradiography and immunohistochemistry (IHC). Mice with BxPC-3 xenografts were imaged with (123)I or (99)TcO(4) micro-SPECT/CT. Tumor dimensions and radionuclide localization were determined with imaging software. Linear regression and correlation analyses were performed to determine the relationship between tumor infection percentage and radionuclide uptake (% injected dose per gram) above background and a highly significant correlation was observed (r(2)=0.947). A detection threshold of 1.5-fold above the control tumor uptake (background) yielded a sensitivity of 2.7% MV-NIS-infected tumor cells. We reliably resolved multiple distinct intratumoral zones of infection from non-infected regions. Pinhole micro-SPECT/CT imaging using the NIS reporter demonstrated precise localization and quantitation of oncolytic MV-NIS infection, and can replace more time-consuming and expensive analyses (for example, autoradiography and IHC) that require animal killing.
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Penheiter
authors.forename: G E
authors.initials: GE
authors.lastname: Griesmann
authors.forename: M J
authors.initials: MJ
authors.lastname: Federspiel
authors.forename: D
authors.initials: D
authors.lastname: Dingli
authors.forename: S J
authors.initials: SJ
authors.lastname: Russell
authors.forename: S K
authors.initials: SK
authors.lastname: Carlson
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging; D050504:Oncolytic Viruses / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D027981:Symporters / Q000235:genetics / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon; D014183:Transplantation, Heterologous; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters