Department of Radiology, Stanford University, Stanford, California.
Department of Radiation Oncology, Stanford University, Stanford, California.
Int J Radiat Oncol Biol Phys. 2023 Jul 15;116(4):927-934. doi: 10.1016/j.ijrobp.2023.01.007. Epub 2023 Jan 18.
Biology-guided radiation therapy (BgRT) uses real-time line-of-response data from on-board positron emission tomography (PET) detectors to guide beamlet delivery during therapeutic radiation. The current workflow requires F-fluorodeoxyglucose (FDG) administration daily before each treatment fraction. However, there are advantages to reducing the number of tracer injections by using a PET tracer with a longer decay time. In this context, we investigated Zr-panitumumab (Zr-Pan), an antibody PET tracer with a half-life of 78 hours that can be imaged for up to 9 days using PET.
The BgRT workflow was evaluated preclinically in mouse colorectal cancer xenografts (HCT116) using small-animal positron emission tomography/computed tomography (PET/CT) for imaging and image-guided kilovoltage conformal irradiation for therapy. Mice (n = 5 per group) received 7 MBq of Zr-Pan as a single dose 2 weeks after tumor induction, with or without fractionated radiation therapy (RT; 6 × 6.6 Gy) to the tumor region. The mice were imaged longitudinally to assess the kinetics of the tracer over 9 days. PET images were then analyzed to determine the stability of the PET signal in irradiated tumors over time.
Mice in the treatment group experienced complete tumor regression, whereas those in the control group were killed because of tumor burden. PET imaging of Zr-Pan showed well-delineated tumors with minimal background in both groups. On day 9 postinjection, tumor uptake of Zr-Pan was 7.2 ± 1.7 in the control group versus 5.2 ± 0.5 in the treatment group (mean percentage of injected dose per gram of tissue [%ID/g] ± SD; P = .07), both significantly higher than FDG uptake (1.1 ± 0.5 %ID/g) 1 hour postinjection. To assess BgRT feasibility, the clinical eligibility criteria was computed using human-equivalent uptake values that were extrapolated from preclinical PET data. Based on this semiquantitative analysis, BgRT may be feasible for 5 consecutive days after a single 740-MBq injection of Zr-Pan.
This study indicates the potential of long-lived antibody-based PET tracers for guiding clinical BgRT.
生物学引导的放射治疗（BgRT）使用实时射线响应数据来自机载正电子发射断层扫描（PET）探测器在治疗放射期间引导射束输送。目前的工作流程要求在每次治疗前每天给予 F-氟脱氧葡萄糖（FDG）。然而，通过使用半衰期更长的示踪剂来减少示踪剂注射次数具有优势。在这种情况下，我们研究了 Zr-帕尼单抗（Zr-Pan），一种半衰期为 78 小时的抗体 PET 示踪剂，使用 PET 最多可在 9 天内进行成像。
使用小动物正电子发射断层扫描/计算机断层扫描（PET/CT）进行成像和图像引导千伏适形照射治疗，在小鼠结直肠癌异种移植（HCT116）中对 BgRT 工作流程进行了临床前评估。每组 5 只小鼠（n=5）在肿瘤诱导后 2 周内接受 7 MBq 的 Zr-Pan 单次剂量，或接受肿瘤区域的分次放射治疗（RT；6×6.6 Gy）。对小鼠进行纵向成像，以评估示踪剂在 9 天内的动力学。然后分析 PET 图像以确定 PET 信号在随时间变化的照射肿瘤中的稳定性。
治疗组的小鼠经历了完全的肿瘤消退，而对照组的小鼠则因肿瘤负担过重而死亡。Zr-Pan 的 PET 成像显示两组均有肿瘤边界清晰，背景最小。注射后第 9 天，对照组肿瘤摄取 Zr-Pan 为 7.2±1.7，治疗组为 5.2±0.5（每克组织的注射剂量百分比 [%ID/g]±SD；P=0.07），均显著高于注射后 1 小时的 FDG 摄取（1.1±0.5 %ID/g）。为了评估 BgRT 的可行性，使用从临床前 PET 数据推断出的人类等效摄取值计算了临床合格标准。基于这项半定量分析，单次注射 740 MBq 的 Zr-Pan 后，连续 5 天进行 BgRT 可能是可行的。
这项研究表明，长寿命抗体基 PET 示踪剂在指导临床 BgRT 方面具有潜力。
