PET with 89Zr-bevacizumab found promising to guide therapy in children with Diffuse Intrinsic Pontine Glioma

The latest issue of the Journal of Nuclear Medicine (May 2017) features a novel strategy that may help guide therapy in children with brain tumors. The Featured Article of the Month [1] describes the application of a molecular drug imaging technology for the first time in children with Diffuse Intrinsic Pontine Glioma (DIPG), and shows promise of filling the existing gap in predictive tools for such young patients.

The team of investigators from the VU University Medical Center (Amsterdam, The Netherlands) verified whether the monoclonal antibody (mAb) bevacizumab, labeled with 89Zr, was able to reach tumors in children with DIPG, by quantifying its uptake by the tumors via PET. The occurrence of adverse events and the biodistribution of 89Zr-bevacizumab were also recorded.

For this, seven young DIPG patients (ages 6–17 years) were injected with 89Zr-bevacizumab (0.1 mg/kg; 0.9 MBq/kg) at least two weeks after completing radiotherapy. All patients underwent whole-body PET/CT scans at 1 h, 72 h and 144 h post-administration, as well as contrast (gadolinium)-enhanced MRI, without anesthesia.

The results attested the safety of the procedure, with no adverse events being registered. Five of seven primary tumors presented a focal uptake of 89Zr-bevacizumab (with SUVs of 1.0–6.7 at 144 h post-injection), without any significant uptake by the healthy portion of the brain. One patient with multiple metastases had positive PET results for all of them. Inter- and intramural heterogeneity of uptake was verified. Uptake of the labeled mAb was detected predominantly (80% of patients) within MRI contrast-enhanced areas, albeit at variable levels. Moreover, the results for tumor targeting were quantitatively similar at 72 h and 144 h post-injection.

In conclusion, PET analyses using 89Zr-bevacizumab can be considered feasible for application in children with DIPG. The obtained results indicate that drug delivery is heterogeneous among patients and within DIPG tumors. Moreover, there seems to be a positive (though not equivalent) correlation between contrast enhancement of MRI and uptake of 89Zr-bevacizumab. The application of PET-imaging using 89Zr-bevacizumab may help identify those patients with greatest chances of benefiting from treatment with bevacizumab.

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[1] Jansen MH, Veldhuijzen van Zanten SEM, van Vuurden DG, Huisman MC, Vugts DJ, Hoekstra OS, van Dongen GA, Kaspers GL. Molecular Drug Imaging: 89Zr-Bevacizumab PET in Children with Diffuse Intrinsic Pontine Glioma. J Nucl Med 2017; 58:711–716. PMID: 27765855.