Noninvasive dual-imaging methods that provide an early readout on tumor permissiveness to virus infection and tumor cell death could be valuable in optimizing development of oncolytic virotherapies. Here, we have used the sodium iodide symporter (NIS) and ¹²⁵I radiotracer to detect infection and replicative spread of an oncolytic vesicular stomatitis virus (VSV) in VSV-susceptible (MPC-11 tumor) versus VSV-resistant (CT26 tumor) tumors in BALB/c mice. In conjunction, tumor cell death was imaged simultaneously using technetium (^99mTc)-duramycin that binds phosphatidylethanolamine in apoptotic and necrotic cells. Dual-isotope single-photon emission computed tomography/computed tomography (SPECT/CT) imaging showed areas of virus infection (NIS and ¹²⁵I), which overlapped well with areas of tumor cell death (^99mTc-duramycin imaging) in susceptible tumors. Multiple infectious foci arose early in MPC-11 tumors, which rapidly expanded throughout the tumor parenchyma over time. There was a dose-dependent increase in numbers of infectious centers and ^99mTc-duramycin-positive areas with viral dose. In contrast, NIS or duramycin signals were minimal in VSV-resistant CT26 tumors. Combinatorial use of NIS and ^99mTc-duramycin SPECT imaging for simultaneous monitoring of oncolytic virotherapy (OV) spread and the presence or absence of treatment-associated cell death could be useful to guide development of combination treatment strategies to enhance therapeutic outcome.

提供对肿瘤对病毒感染的允许性和肿瘤细胞死亡的早期读取的非侵入性双成像方法，对于优化溶瘤病毒疗法的发展可能是有价值的。在这里，我们已经使用碘化钠共转运蛋白（NIS）和¹²⁵ I放射性示踪剂来检测易溶性水疱性口炎病毒（VSV）在易感VSV的病毒（MPC-11肿瘤）相对于对VSV耐药的CT26肿瘤中的感染和复制扩散在BALB / c小鼠中。结合起来，使用tech （^99m Tc）-杜拉霉素同时结合凋亡细胞和坏死细胞中的磷脂酰乙醇胺，对肿瘤细胞死亡进行成像。双同位素单光子发射计算机断层扫描/计算机断层扫描（SPECT / CT）成像显示病毒感染区域（NIS和¹²⁵I）与易感肿瘤中的肿瘤细胞死亡区域（^99m Tc-杜拉霉素成像）重叠良好。MPC-11肿瘤早期出现了多个传染病灶，随着时间的推移，该病灶在整个肿瘤实质中迅速扩大。随着病毒剂量的增加，感染中心和^99m Tc-杜拉霉素阳性区域的数量呈剂量依赖性。相反，在VSV耐药的CT26肿瘤中，NIS或杜拉霉素信号最小。NIS与^99m Tc-杜拉霉素SPECT成像的组合使用同时监测溶瘤病毒疗法（OV）的扩散以及是否存在与治疗相关的细胞死亡可能对指导联合治疗策略的开发以增强治疗效果很有用。