Purpose: Biology-guided radiation therapy (BgRT) uses real-time line-of-response data to guide beamlet delivery during therapeutic radiation. However, the current workflow requires FDG administration daily prior to each RT fraction. Long-lived antibody-based PET imaging could simplify the BgRT procedure by reducing the number of tracer injections, while potentially improving guidance accuracy.
Methods: 89Zr-Panitumumab is a 78 h-half-life PET tracer targeting the epidermal growth factor receptor (EGFR) in tumors. The BgRT workflow was evaluated pre-clinically in mouse colorectal cancer xenografts (HCT116) using small-animal PET/CT for imaging, and image-guided kilovoltage conformal irradiation for therapy. Each mouse received 200 uCi of tracer as a single dose 2 weeks after tumor induction. In the control group (n=4), the mice were imaged longitudinally to assess the kinetics of the tracer over 9 days. In the treatment group (n=4), the mice additionally received 6x5 Gy to the tumor region. PET images were analyzed to determine the stability of the PET signal in irradiated mice.
Results: RT resulted in >50% tumor volume reduction compared to untreated controls (p= 0.001). All mice in the treatment group survived >50 days, compared to those in the control group that were sacrificed due to tumor burden. Specific tracer uptake in the tumor was observed in both groups and up to 9 days after injection, showing well delineated tumors with minimal background. The final tumor uptake was 7.2 ± 1.7 in the control group vs 5.2 ± 0.5 in the treated group (mean %ID/g ± SD; P = 0.07).
Conclusion: Long-lived antibody PET imaging demonstrated tumor-specific uptake for up to 9 days after single-dose tracer administration, even after 6x5 Gy irradiation, with only moderate loss of signal (<30%). This study demonstrates the potential utility of a 89Zr antibody PET tracer for clinical BgRT.
Funding Support, Disclosures, and Conflict of Interest: Funding for this work was provided by Reflexion Medical Inc.
PET, Image Guidance, Radiation Therapy
TH- External Beam- Photons: onboard imaging (development and applications)