title: Mesenchymal Stem Cell-mediated delivery of the sodium iodide symporter supports radionuclide imaging and treatment of breast cancer.
abstract: Mesenchymal Stem Cells (MSCs) migrate specifically to tumors in vivo, and coupled with their capacity to bypass immune surveillance, are attractive vehicles for tumor-targeted delivery of therapeutic agents. This study aimed to introduce MSC-mediated expression of the sodium iodide symporter (NIS) for imaging and therapy of breast cancer. Tumor bearing animals received an intravenous or intratumoral injection of NIS expressing MSCs (MSC-NIS), followed by (99m) Technetium pertechnetate imaging 3-14 days later using a BazookaSPECT γ-camera. Tissue was harvested for analysis of human NIS (hNIS) expression by relative quantitative-polymerase chain reaction. Therapy animals received an i.p. injection of (131) I or saline 14 days after injection of MSC-NIS, and tumor volume was monitored for 8 weeks. After injection of MSC-NIS, BazookaSPECT imaging revealed an image of animal intestines and chest area at day 3, along with a visible weak tumor image. By day 14, the tumor was visible with a significant reduction in radionuclide accumulation in nontarget tissue observed. hNIS gene expression was detected in the intestines, heart, lungs, and tumors at early time points but later depleted in nontarget tissues and persisted at the tumor site. Based on imaging/biodistribution data, animals received a therapeutic dose of (131) I 14 days after MSC-NIS injection. This resulted in a significant reduction in tumor growth (mean ± SEM, 236 ± 62 mm(3) vs. 665 ± 204 mm(3) in controls). The ability to track MSC migration and transgene expression noninvasively in real time before therapy is a major advantage to this strategy. This promising data supports the feasibility of this approach as a novel therapy for breast cancer.
authors: Discipline of Surgery, National University of Ireland Galway, Ireland. roisin.dwyer@nuigalway.i.e
authors: Roisin M
authors: RM
authors: Dwyer
authors: James
authors: J
authors: Ryan
authors: Ronan J
authors: RJ
authors: Havelin
authors: John C
authors: JC
authors: Morris
authors: Brian W
authors: BW
authors: Miller
authors: Zhonglin
authors: Z
authors: Liu
authors: Richard
authors: R
authors: Flavin
authors: Cathal
authors: C
authors: O'Flatharta
authors: Mark J
authors: MJ
authors: Foley
authors: Harrison H
authors: HH
authors: Barrett
authors: J Mary
authors: JM
authors: Murphy
authors: Frank P
authors: FP
authors: Barry
authors: Timothy
authors: T
authors: O'Brien
authors: Michael J
authors: MJ
authors: Kerin
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