Abstract
Predictive tools to guide therapy in children with brain tumors are urgently needed. We introduced molecular imaging to facilitate this. We investigated whether bevacizumab can reach the tumor in children with diffuse intrinsic pontine glioma (DIPG) by measuring the tumor uptake of zirconium-89(89Zr)-labeled bevacizumab by PET. In addition we evaluated the safety of the procedure in children and determined the optimal timing of imaging. Methods: Patients received 0.1 mg/kg (0.9 MBq/kg) 89Zr-bevacizumab, ≥ two weeks after completing radiotherapy. Whole body PET-CT scans were performed 1, 72 and 144 hours post-injection (p.i.). All patients underwent contrast (gadolinium)-enhanced MRI. Biodistribution of 89Zr-bevacizumab was quantified as Standardized Uptake Values (SUVs). Results: We included seven DIPG patients (4 males, age range 6-17 years) who were scanned without anesthesia. No adverse events occurred. Five out of seven primary tumors showed focal 89Zr-bevacizumab uptake (SUVs range 1.0-6.7 at 144 hours p.i.), while there was no significant uptake in healthy brain. One patient had multiple metastases, which were all PET positive. There was inter- and intra-tumoral heterogeneity of uptake and 89Zr-bevacizumab was predominantly (in 4 out of 5 patients) present within the MRI contrast-enhancing areas, although 89Zr-bevacizumab uptake was variable among MRI contrast-enhancing areas. Tumor targeting was quantitatively similar at 72 and 144 hours post-injection, but tumor-to-blood SUV ratios increased over post-injection time (P = 0.045). The mean effective dose per patient was 0.9±0.3 mSv/MBq. Conclusion: 89Zr-bevacizumab PET-studies are feasible in children with DIPG. The data suggest considerable heterogeneity in drug delivery between patients and within DIPG tumors and a positive, but not 1-to-1, correlation between MRI contrast-enhancement and 89Zr-bevacizumab uptake. The optimal moment of scanning is 144 hours p.i.. Tumor 89Zr-bevacizumab accumulation as assessed by PET scanning might help to select patients with highest chance of benefit from bevacizumab treatment.
- Oncology: Brain
- Pediatrics
- Radiopharmaceuticals
- 89Zr-bevacizumab
- Brainstem neoplasm
- Diffuse Intrinsic Pontine Glioma
- Pharmacokinetics
- Positron Emission Tomography
- Copyright © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.