11C-erlotinib brain uptake in Diffuse Intrinsic Pontine Glioma imaged by PET

Diffuse Intrinsic Pontine Glioma (DIPG) has an extremely poor prognoses and is
one of the main causes of cancer death in children. Previous studies
demonstrated that the Epithelial Growth Factor Receptor (EGFR) is overexpressed
in a significant subset of DIPG patients. EGFR promotes tumor growth and
invasion. Erlotinib targets this overexpression as a small-molecule EGFR-TKI
and has been consistently demonstrated as a safe and well-tolerated therapy in
pediatric glioma patients. Without compromising its structural integrity,
erlotinib can be radiolabeled with carbon-11 (11C). 11C imaging has been safely
and successfully used in previous imaging studies to identify
treatment-sensitive cancers. In this study erlotinib is microdosed, resulting
in no systemic side effects. The PET imaging coudl demonstrate whether or not
some tumors actually show drug uptake. This would allow more individualized
efficacy studies, selecting only patients with drug uptake in their tumor,
preventing (continuation of) treatment of patients that do not show uptake.

Primary objective:
Non-invasively determining the 11C-erlotinib brain uptake in DIPG patients by
PET imaging.

Secondary objective:
Determining the EGFR expression in DIPG

This is a single center, non-randomized, open label drug imaging study.
Patients receive 10 ml of 11C-erlotinib; 370 MBq/16,2 µg IV at least 2 weeks
after the start of erlotinib therapy. A PET-scan will be performed 40 minutes
post-injection (p.i). The PET scan will be preceded by a low-dose CT. Following
the CT, a 20 min static PET scan will be performed covering the brain. Directly
before and after a PET-CT scan is made, a venous blood sample is taken.

IV infusion of 11C-erlotinib, once

Risks:
This is an imaging study in patients with a very poor prognosis. Labelled
erlotinib, used as a tracer, is administered in a microdose of 16,2 µg
(therapeutic dose 85-125 mg/m2). Therefore, no adverse events of erlotinib are
expected.
All patients will be or have been irradiated, usually with a total dose of 54
Gy. Patients receive a total dose of 370 MBq/16,2 µg 11C-erlotinib, which
results in an expected radiation dose of 2 mSv. An additional 1,5 mSv will be
added by the low dose CT scans for the PET/CT examination. The total radiation
burden of the brain PET/CT examinations will be 3,5 mSv. The radiation burden
added by this study is therefore, negligible.

Burden:
All participants receive two IV cannula and undergo one brain PET scan.
Therefore, they have to lay down quietly for 30 minutes. No anesthesia will be
used. Our standardized training program enables children from four years and
older to undergo MRI without major problems. An advantage of PET is that the
quality of the images are less influenced by small movements compared to MRI.
We are certainly aware of the burden, but in our opinion, the scientific value
of this project outweighs this concern, because response prediction in patients
may lead to effective personalized cancer treatment and helps to avoid the
administration of inactive drugs and the accompanying side effects in the
future. With regard to the latter, we propose that the burden of this study
outweighs the unnecessary (and much higher) burden of patients treated with
ineffective drugs. PET-erlotinib studies have not been applied in children with
DIPG yet: these studies are necessary since biology including receptor kinase
expression clearly differs from adult gliomas.