Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, California.
J Nucl Med. 2012 Feb;53(2):312-317. doi: 10.2967/jnumed.111.094623. Epub 2012 Jan 12.
Cerenkov luminescence imaging (CLI) has emerged as a less expensive, easier-to-use, and higher-throughput alternative to other nuclear imaging modalities such as PET. It is expected that CLI will find many applications in biomedical research such as cancer detection, probe development, drug screening, and therapy monitoring. In this study, we explored the possibility of using CLI to monitor drug efficacy by comparisons against PET. To assess the performance of both modalities in therapy monitoring, 2 murine tumor models (large cell lung cancer cell line H460 and prostate cancer cell line PC3) were given bevacizumab versus vehicle treatments. Two common radiotracers, 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) and (18)F-FDG, were used to monitor bevacizumab treatment efficacy.
One group of mice (n = 6) was implanted with H460 xenografts bilaterally in the shoulder region, divided into treatment and control groups (n = 3 each), injected with (18)F-FLT, and imaged with PET immediately followed by CLI. The other group of mice (n = 6) was implanted with PC3 xenografts in the same locations, divided into treatment and control groups (n = 3 each), injected with (18)F-FDG, and imaged by the same modalities. Bevacizumab treatment was performed by 2 injections of 20 mg/kg at days 0 and 2.
On (18)F-FLT scans, both CLI and PET revealed significantly decreased signals from H460 xenografts in treated mice from pretreatment to day 3. Moderately increased to unchanged signals were observed in untreated mice. On (18)F-FDG scans, both CLI and PET showed relatively unchanged signals from PC3 tumors in both treated and control groups. Quantifications of tumor signals of Cerenkov luminescence and PET images showed that the 2 modalities had excellent correlations (R(2) > 0.88 across all study groups).
CLI and PET exhibit excellent correlations across different tumor xenografts and radiotracers. This is the first study, to our knowledge, demonstrating the use of CLI for monitoring cancer treatment. The findings warrant further exploration and optimization of CLI as an alternative to PET in preclinical therapeutic monitoring and drug screening.
切伦科夫发光成像是一种成本更低、使用更方便、通量更高的替代其他核成像方式，如 PET。预计切伦科夫发光成像将在癌症检测、探针开发、药物筛选和治疗监测等生物医学研究中得到广泛应用。在这项研究中，我们通过与 PET 的比较，探索了使用切伦科夫发光成像来监测药物疗效的可能性。为了评估两种模态在治疗监测中的性能，我们使用 2 种常见的放射性示踪剂 3'-去氧-3'-(18)F-氟代胸苷（(18)F-FLT）和 (18)F-FDG，监测贝伐单抗的治疗效果。
一组小鼠（n=6）在肩部双侧植入 H460 异种移植物，分为治疗组和对照组（n=3 只），注射 (18)F-FLT，并立即进行 PET 成像和 CLI 成像。另一组小鼠（n=6）在相同部位植入 PC3 异种移植物，分为治疗组和对照组（n=3 只），注射 (18)F-FDG，并用相同的方式进行成像。贝伐单抗治疗采用 2 次 20mg/kg 的剂量，分别在第 0 天和第 2 天注射。
在 (18)F-FLT 扫描中，CLI 和 PET 均显示治疗组小鼠从预处理到第 3 天 H460 异种移植物的信号明显降低。未治疗组的信号中度增加或不变。在 (18)F-FDG 扫描中，CLI 和 PET 显示治疗组和对照组 PC3 肿瘤的信号相对不变。Cerenkov 发光和 PET 图像的肿瘤信号定量分析表明，两种模态具有很好的相关性（所有研究组的 R(2)>0.88）。
CLI 和 PET 在不同的肿瘤异种移植和放射性示踪剂中具有很好的相关性。这是我们所知的首次使用 CLI 监测癌症治疗的研究。这些发现值得进一步探索和优化 CLI 作为 PET 在临床前治疗监测和药物筛选中的替代方法。
