Biomedical Imaging Group, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts 02139, USA.
J Nucl Med. 2011 Nov;52(11):1764-9. doi: 10.2967/jnumed.111.091710. Epub 2011 Oct 12.
Cerenkov luminescence imaging (CLI) is an emerging imaging technique that combines aspects of both optical and nuclear imaging fields. The ability to fully evaluate the correlation and sensitivity of CLI to PET is critical to progress this technique further for use in high-throughput screening of pharmaceutical compounds. To achieve this milestone, it must first be established that CLI data correlate to PET data in an in vivo preclinical antitumor study. We used MLN4924, a phase 2 oncology therapeutic, which targets and inhibits the NEDD8-activating enzyme pathway involved in the ubiquitin-proteasome system. We compared the efficacious effects of MLN4924 using PET and Cerenkov luminescence image values in the same animals.
Imaging of (18)F-FDG uptake was performed at 5 time points after drug treatment in the subcutaneously implanted diffuse large B-cell lymphoma tumor line OCI-Ly10. Data were acquired with both modalities on the same day, with a 15-min delay between CLI and PET. PET data analysis was performed using percentage injected dose per cubic centimeter of tissue (%ID/cm(3)), average standardized uptake values, and total glycolytic volume. CLI measurements were radiance, radiance per injected dose (radiance/ID), and total radiant volume.
A strong correlation was found between PET total glycolytic volume and CLI total radiant volume (r(2) = 0.99) and various PET and CLI analysis methods, with strong correlations found between PET %ID/cm(3) and CLI radiance (r(2) = 0.83) and CLI radiance/ID (r(2) = 0.82). MLN4924 demonstrated a significant reduction in tumor volume after treatment (volume ratio of treated vs. control, 0.114 at day 29).
The PET and CLI data presented confirm the correlation and dynamic sensitivity of this new imaging modality. CLI provides a preclinical alternative to expensive PET instrumentation. Future high-throughput studies should provide for quicker turnaround and higher cost-to-return benefits in the drug discovery process.
切伦科夫发光成像（CLI）是一种新兴的成像技术，结合了光学和核成像领域的多个方面。充分评估 CLI 与 PET 的相关性和灵敏度对于进一步推进该技术在药物化合物高通量筛选中的应用至关重要。要实现这一里程碑，首先必须确定 CLI 数据在体内抗肿瘤研究中与 PET 数据相关。我们使用了 MLN4924，这是一种针对并抑制参与泛素-蛋白酶体系统的 NEDD8 激活酶途径的 2 期肿瘤治疗药物。我们比较了 MLN4924 在同一动物中使用 PET 和切伦科夫发光图像值的疗效。
在皮下植入弥漫性大 B 细胞淋巴瘤肿瘤细胞系 OCI-Ly10 后，在 5 个时间点进行（18）F-FDG 摄取的成像。两种方式均在同一天进行数据采集，CLI 和 PET 之间有 15 分钟的延迟。PET 数据分析采用每立方厘米组织的注射剂量百分比（%ID/cm(3)）、平均标准化摄取值和总糖酵解体积。CLI 测量值为辐射率、每注射剂量的辐射率（辐射率/ID）和总辐射体积。
发现 PET 总糖酵解体积与 CLI 总辐射体积之间存在很强的相关性（r(2) = 0.99），以及各种 PET 和 CLI 分析方法之间存在很强的相关性，PET %ID/cm(3)与 CLI 辐射率（r(2) = 0.83）和 CLI 辐射率/ID（r(2) = 0.82）之间存在很强的相关性。MLN4924 治疗后肿瘤体积明显缩小（治疗后与对照的体积比为 0.114，第 29 天）。
所呈现的 PET 和 CLI 数据证实了这种新成像模式的相关性和动态灵敏度。CLI 为昂贵的 PET 仪器提供了一种临床前替代方案。未来的高通量研究应在药物发现过程中提供更快的周转时间和更高的成本回报效益。
