Preclinical Evaluation of ⁸⁹Zr-Panitumumab for Biology-Guided Radiation Therapy

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 ¹⁸F-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 ⁸⁹Zr-panitumumab (⁸⁹Zr-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 ⁸⁹Zr-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 ⁸⁹Zr-Pan showed well-delineated tumors with minimal background in both groups. On day 9 postinjection, tumor uptake of ⁸⁹Zr-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 ⁸⁹Zr-Pan.

This study indicates the potential of long-lived antibody-based PET tracers for guiding clinical BgRT.