To increase insight in the glucose metabolism in surgically treated PPGL patients by using dynamic FDG-PET/CT for analysis of tumor metabolic activity, blood fraction and full pharmacokinetic parameters. Furthermore, to correlate these finding with…
ID
Source
Brief title
Condition
- Neoplastic and ectopic endocrinopathies
- Endocrine neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To increase insight in the in vivo glucose metabolism in PPGL by performing
pharmacokinetic analyses of dynamic FDG-PET/CT scanning.
Secondary outcome
- To assess the genotypic specific differences in glucose metabolism across
sporadic and hereditary PPGLs and to evaluate whether higher FDG-PET/CT SUV
observed in SDHx and VHL-related PPGL is a reflection of an increased FDG
uptake and/or metabolism as a reflection the Warburg effect.
- To investigate whether quantitative dynamic FDG-PET/CT parameters correlate
with tumor histology and tissue markers of glucose metabolism (GLUT-1, GLUT-3,
HK-2, HK-3 and MCT-4) and vascularity (VEGF, CD34).
Background summary
Among pheochromoyctomas and paragangliomas (PPGLs), malignant tumors have a
frequency of about 14%, but are more frequent (up to 50%) in patients with
mutations in succinate dehydrogenase subunit B (SDHB). Functional imaging is
widely used for the localization of PPGL. FDG-PET/CT serves as biomarker of
tumor cell viability and proliferative activity and provides a high sensitivity
for the detection of metastases, especially in carriers of underlying germline
SDHB-gene mutations, in which it is superior to other techniques. The molecular
mechanisms linking SDH mutations to tumorgenesis are starting to be unraveled.
Whether genotype-related differences in mitochondrial function and associated
changes in cellular energy metabolism are mirrored by differences in in vivo
FDG uptake has not been elucidated. Different techniques can be used to
quantify and localize glucose uptake on FDG-PET/CT scans. Preliminary results
show genotypic differences in glucose uptake in static (single timeframe)
FDG-PET. However, static FDG-PET/CT has its limitations in exact quantification
of glucose uptake. Pharmacokinetic analysis using dynamic (multi-timeframe)
FDG-PET/CT is supposed to more accurately quantify glucose metabolism and
findings might correlate better with pathology results.
Study objective
To increase insight in the glucose metabolism in surgically treated PPGL
patients by using dynamic FDG-PET/CT for analysis of tumor metabolic activity,
blood fraction and full pharmacokinetic parameters. Furthermore, to correlate
these finding with histological findings to come to in vivo predictive
biological profile. Finally, to assess genotypic specific differences in
glucose uptake and metabolism in sporadic and hereditary PPGL.
Study design
Observational pilot study using one group of patients. Pathologist and nuclear
medicine physicians are blinded for each others results.
Study burden and risks
For this study, patients undergo an alternative protocol for FDG PET/CT
scanning. The PET/CT scan itself is already part of the regular diagnostic
workup for patients with PPGL. The additional load for patients will be that
they are already lying still in the PET/CT scanner during incubation with 18FDG
(and images will be taken simultaneously). Usually during incubation time,
patients do lie in a bed in a quiet room. The radionuclide is administered into
a brachial vein through an intravenous line. Approximately 1,6MBq.kg-1 FDG is
injected. This is similiar to the dose needed for the routine diagnostic static
FDG-PET/CT scan. So, no additional FDG will be administered for this study. An
additional intravenous cannula is placed in the antecubital vein. One blood
sample is drawn from that cannula for correction of the input function. The
dynamic FDG-PET/CT scan will take approximately 55 minutes and the static whole
body FDG-PET/CT scan will take another 25 minutes (including preparation).
Patients are allowed to go to the toilet between dynamic and static scanning.
So, patients will in total be for ~ 1 hour and 20 minutes in the FDG-PET/CT
scanner. An additional topogram (~0,1 mSv) and low dose CT of the abdomen
(~2,04 mSv) will be made for dynamic scanning.
Individual benefit is limited to possible extra clinical relevant data as to
PPGL tumor behaviour and prognosis.
Geert Grooteplein Zuid 8
Nijmegen 6500 HB
NL
Geert Grooteplein Zuid 8
Nijmegen 6500 HB
NL
Listed location countries
Age
Inclusion criteria
- Age >= 18 years, no upper limit
- Suspected diagnosis of benign PCC or PGL:
1. Biochemically proven by elevated plasma and/or urinary (nor)metanephrines
2. Anatomically substrate; localization of an (extra)-adrenal tumor by conventional anatomical (MRI/CT) imaging
- Regardless of the genetic status (sporadic or hereditary)
- Planned for surgical resection (adrenalectomy or extra-adrenal tumor resection)
- Size tumor at least 1 cm in smallest diameter (as determined by conventional imaging)
Exclusion criteria
- Malignant PPGL, i.e. presence of lesions on imaging studies suggestive of distant metastasis
- No initial CT or MRI available
- Contra-indication for surgery:
o Based on (biological) age, cardiovascular risk factors, performance status or other co-morbidity as decided by a multidisciplinary team including medical endocrinologist, urologists, radiologists, pathologists and nuclear medicine physicians.
- Contra-indication for dynamic FDG-PET/CT
o Diabetes mellitus or fasted glucose level >= 8.0 mmol.L-1
o Pregnancy
o Breast-feeding
o Sever claustrophobia
- Interval between dynamic FDG-PET/CT and surgery more than 60 days
- Incapability to adhere to study protocol
- Inability to give informed consent (e.g. psychiatric illness)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL45529.091.13 |