Towards endoscopic ultrasound and 11C-5-HTP PET screening for pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 and Von Hippel Lindau disease

Multiple Endocrine Neoplasia type 1 (MEN1) and Von Hippel-Lindau disease (VHL)
are rare autosomal dominantly inherited disorders characterized by the
occurrence of various tumors. Therefore, mutation carriers undergo regular
screening (yearly for VHL and three yearly for MEN1) to enable early treatment.
With earlier detection of treatable tumors, e.g. renal cell carcinoma in VHL
patients, survival is improving. This increases however the chance to develop
other tumor types such as pancreatic neuroendocrine tumors (NET) to occur.
Pancreatic NETs develop in MEN1 in 65% and in VHL in 10-20%, and is the second
most frequent tumor manifestation in MEN1 patients. Pancreatic NETs are
discovered in an advanced stage by serum markers (e.g. insulin, chromogranin
A). Non-functioning pancreatic NETs are even more difficult to detect at early
stage with currently available imaging modalities, while early detection would
allow sparing curative surgery. Standard regular screening for pancreatic NETs
consists of ultrasound, MRI, CT and somatostatin receptor scintigraphy (SRS).
However, the sensitivity of these techniques is limited.
Two new imaging strategies have emerged. Endoscopic ultrasound (EUS) with fine
needle aspiration (FNA) for cytology with an estimated sensitivity of 80% and
positron emission tomography (PET) using the serotonin (5-HTP) precursor tracer
11C-5-HTP. EUS with FNA of pancreatic lesions is still a specialized technique
performed in a few Dutch centers among which the UMCG. We recently showed that
11C-5-HTP PET imaging is superior to conventional imaging in the detection of
pancreatic NETs. The UMCG is one of the three centers worldwide that have this
technique available. Introduction of these two techniques will most likely
improve early NET detection and allow sparing curative surgery in these high
risk individuals for pancreatic NET.
Early detection allowing surgery with selective extirpation of pancreatic NET,
which will most likely increase life expectancy and quality of life in these
patients.

To determine the additiotinal value of EUS and 11C-5-HTP PET scan for detection
of pancreatic NET.

EUS*FNA and 11C-5-HTP PET will be performed in the UMCG

Radio activity

5-HTP-PET Scanning takes a visit of 2 * hours. Eating is not allowed 2 hours
before the examination, but the planning at the end of the morning makes it
possible to eat a light breakfast. An intravenous catheter will be placed for
taking a blood sample and for application of the radio active labelled
compound. During the scan 1 hour of rest and laying down is necessary.

Side effect, other risks and discomforts. Advantages and disadvantages of the
HTP-PET:


- no side effects can be expected from the PET scan for the applicated dosage
is very low
- 2 hours without eating can be uncomfortable
- pricking can hurt and result in a temporally local blue discolouring of the
skin
- 50 ml blood will be taken for blood count and kidney function control
- the results of the PET scan can result in another diagnostic procedure, this
is not known before

PET uses radio active labelled compounds. This study is about 11C-5-HTP.
Within 11C-5-HTP. there is a C-atom radio active marked. There are no side
effects of the injection with 11C-5-HTP. The radio activity will be rapidly
removed: after 20 minutes the half of the radio activity has been disappeared.
The amount of radiation is comparable with the amount of natural radiation the
Netherlands (1,7 mSv/year). The guidelines for radio active exposure has been
defined in *Besluit Stralingsbescherming* (BS 2000), article 60, Staatsblad
2001, 397*,referring to international guidelines of the International
Commission on Radiological Protection (ICRP 62). The amount of radiation of
only-once 11C-5-HTP PET scan is a categorie IIB (small to middle risk level)
1-10 mSv).
Because of the radiation, pregnant women are not allowed to take part on this
study.

For this ultrasound patients,- planned after the PET scan- they are not allowed
to eat, drink or smoke. Medicines can be taken with a little water. Patients
can choose a light sedation but this is not obliged. The procedure is about 30
minutes. The doctor can consider to do an fine needle aspiration from a
pancreas tumor, this punction is hardly felt. There is a minimum risk that this
punction can result in an inflammation of the pancreas. After the research
there will be an observation for minimum 1 and maximum 2 hours, so the patient
can wake up. Because of the anaesthetics the patient isn*t allowed to drive.
After the research the patient can have a sore throat.

Side effect, other risks and discomforts. Advantages and disadvantages of the
endo-ultrasound:
- Before the endo-ultrasound you have to have an empty stomach, this can be
uncomfortable.
- If there is a tumor found in the pancreas, a fine needle aspiration will be
done, this is not painfull but there is a risk of an inflammation of the
pancreas.
- Sedation will be offered, so you do not feel the procedure, but you have to
stay for 1 or 2 hours after the EUS until the sedation has worked out and you
can*t drive.
- You can have a sore throat after the research.