11C-MET PET(/CT) vs 18F-FDG PET(/CT) in the follow-up of differentiated thyroid cancer*

Although FDG PET(/CT), under TSH stimulation, is now considered as a valuable,
established diagnostic imaging tool in the follow-up of 131I-negative patients
for the detection of recurrences or metastases, the interest for new tracers
and improvement of diagnostic tools in thyroid cancer is growing. Another
target for metabolic tumor imaging is the increased protein metabolism and
transport in cancer cells, to which radiolabeled amino acids can be applied.
Amino acid transport is generally increased in malignant tissue, which could be
associated with specific cell surface changes in transformed cells. The process
of malignant transformation requires in general that cells acquire and use
nutrients efficiently for energy, protein synthesis and cell division. Two
major steps are involved in protein metabolism including increased amino acid
transport and protein synthesis. It is imaginable that thyroid cancer could
sufficiently concentrate amino acids due to its protein synthesis (e.g.
thyroglobulin) and the often slowly progressive character in the
well-differentiated tumors (e.g. Hurthlecell carcinoma).

The general feasibility of amino acid imaging with C-11 methionine (MET) PET
under TSH suppression in differentiated thyroid cancer (DTC) has been shown
(Phan et al, in press NMC). Interesting finding in the study of Phan et al. was
the complementary uptake of MET and FDG in 25% of the patients. It has been
hypothesized that this finding might be explained by the degree of tissue
dedifferentiation. Hürthlecell carcinoma are known to be less radioiodine-avid
compared to the well-differentiated papillary and follicular carcinoma or can
be even non-iodine or non-FDG avid. For this group of patients MET PET might be
of complementary value.

In-vitro study in the rat thyroid cells has suggested that the TSH level does
not influence the amino acid uptake. However, no clinical intra-individually
comparative studies between 18F-FDG PET and 11C-MET PET during (rh)TSH
stimulation are available. It would be of interest to evaluate the diagnostic
yield of MET PET scans under (recombinant human, rh)TSH stimulation and to
compare these results with TSH stimulated FDG PET.

- Objective (Study) 1.To evaluate the clinical performance of MET PET during
rhTSH stimulation and to compare the results of this MET PET with the clinical
rhTSH stimulated FDG PET in patients with negative post-treatment 131I-whole
body scan (WBS) and elevated serum thyroglobulin (Tg(on) > 5.0 ng/nl).

- Objective (Study) 2. To evaluate the (complementary) value of (rh)TSH
stimulated MET PET in patients with persistent or recurrent Hürthlecell
carcinoma in the post-ablation phase and during follow-up.

The Department of Internal Medicine * Endocrinology at the UMCG is the largest
treatment center for thyroid cancer in the Netherlands. Since 1978 more than
650 patients have been treated for thyroid cancer. The materials and data of
these patients are collected in a large database. The median follow-up duration
is 11 years (range 1-24 years). Approximately 30-40 patients with DTC are
referred to the UMCG for treatment annually. These patients are seen regularly
at the outpatient clinic for follow-up. Difficult cases are discussed on a
regular base in a multidisciplinary panel consisting of nuclear medicine
physicians, endocrinologists and surgeons.
Patients for these pilot studies are firstly seen by their endocrinologist at
the out-patient clinic for follow-up. In case patients fulfill the inclusion
criteria described below, they will be referred to the department of Nuclear
Medicine and Molecular Imaging (NMMI) for PET scanning as part of clinical
patient care. The duration of these pilot studies is estimated to be 2-3 years.

Study 1: this pilot study evaluates the clinical performance of MET PET during
rhTSH stimulation and to compare the results of the rhTSH stimulated MET PET
with the standard rhTSH stimulated FDG PET in patients with negative
post-treatment 131-I scans and elevated serum thyroglobulin (Tg).

Study 2: this pilot study evaluates the (complementary) value of MET PET in
patients with persistent or recurrent Hürthlecell carcinoma in the
post-ablation phase and during follow-up.

The patient will remain in fasting condition for at least 6 hours prior the
11C-MET PET, however is allowed to drink water and take his medication. At the
time planned 7 MBq/kg 11C-methionine is injected via an intravenous canula
inserted in a vein of a lower forearm. Twenty minutes post-injection of
11C-MET injection the patient will be positioned in the scanner and a
*standard* PET study will be performed in whole body The whole procedure will
take appoximately 90 minutes of which approximately 60 minutes will be spent in
the camera. If possible, the 11C-MET PET and the clinical FDG PET will be
combined on the same day. Patients will be asked to lay quietly during the
scanning procedure.
The effective dose has been calculated at 0.0052 mSv/MBq for 11C-MET. The
radiation dose is 2.9 mSv for a patient weighing 80 kg (7 MBq/kg) for the MET
PET which complies with category IIb, ICRP-62. According to the RIVM the annual
background from natural radiation in the Netherlands is 1.7 mSv. No adverse
effect events are to be expected during the PET scanning. The physical
discomfort during the scanning procedure is minimal.