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.

非侵入性双成像方法可以提供肿瘤对病毒感染和肿瘤细胞死亡的耐受性的早期读数，这对于优化溶瘤病毒疗法的开发具有重要意义。在这里，我们使用碘化钠同向转运体 (NIS) 和¹²⁵ I 放射性示踪剂来检测溶瘤性水泡性口炎病毒 (VSV) 在 VSV 敏感（MPC-11 肿瘤）与 VSV 耐药（CT26 肿瘤）肿瘤中的感染和复制扩散在 BALB/c 小鼠中。同时，使用与凋亡和坏死细胞中的磷脂酰乙醇胺结合的锝 ( ^99m Tc)-耐久霉素同时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¹²⁵ I），与易感肿瘤中的肿瘤细胞死亡区域（ ^99m Tc-耐久霉素成像）重叠良好。 MPC-11 肿瘤早期出现多个感染灶，随着时间的推移，这些感染灶在整个肿瘤实质中迅速扩展。感染中心和^99m Tc-耐久霉素阳性区域的数量随病毒剂量呈剂量依赖性增加。相反，在 VSV 耐药性 CT26 肿瘤中，NIS 或耐久霉素信号微乎其微。组合使用 NIS 和^99m Tc-耐久霉素 SPECT 成像来同时监测溶瘤病毒疗法 (OV) 的扩散以及治疗相关细胞死亡的存在或不存在，可能有助于指导联合治疗策略的开发，以增强治疗效果。