Fluorodopa [F-18] - Thyroid Cancer (Medullary Thyroid Carcinoma)

Medullary thyroid carcinoma (MTC) has different characteristics compared to all other types of thyroid cancer. It starts as an abnormal growth of cancer within the thyroid cells. It produces from the parafollicular C cells of the thyroid gland. These cells make a hormone called calcitonin instead of making thyroid hormone. It is an uncommon neuroendocrine tumor comparing to all other thyroid malignancies in the United States. In order to detect the medullary thyroid carcinoma we use the Positron Emission Tomography (PET) scan.

PET is an imaging test that can detect diseases in your body. The scan uses a special radioactive tracer as a dye that some organs or tissues then absorb. This scan can help the specialists to see the function of the tissue and organ. In medullary thyroid carcinoma we use [F-18] Fluorodopa as a radiotracer. [F-18] Fluorodopa is an amino acid analog used for PET. [F-18]Fluorodopa is an abbreviation of L-3,4-Dihydroxy-6-[18F]fluorophenylalanine. [F-18] Fluorodopa has a physical half-life of 109.

7 minutes, striatum is the mode of uptake, it has 511 (KeV), and it is two photon disintegration. The objective of this research to make the reader able to understand the importance of using [F-18]Fluorodopa with detection of Medullary Thyroid Cancer using PET.

According to ELSEEVIER, the first discovery of the synthesis with [F-18]Fluorodopa was done by Firnau and coworkers in 1973. After that, in 1984 the first [F-18] Fluorodopa PET brain imaging was done to image the dopamineric neurons in basal ganglia.

According to the Society of Nuclear Medicine and Molecular Imaging, (n.

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p.). IASODopa is the drug commercial name that is approved for clinical use in some European countries. This drug has many uses; it is used in Neurology, Psychiatry and Oncology. In Neurology and Psychiatry dopamine receptors in the brain are the target, and they use this drug to diagnose patient with Parkinson’s disease. In Oncology they use it for Amino acid transporters, which are features of many benign and malignant tumors. Also, the characteristic feature of neuroendocrine tumors (NET) is overexpression of DOPA decarboxylase, chromogranin-A is an example of co-expressed with other neuroendocrine markers. This drug is an excellent tracer for imaging NET, including pheochromocytoma and medullary thyroid carcinoma (SNMMI, 2013).

According to Nuclear Medicine Communication, (Chondrogiannis et al., 2013). [F-18] is a positron emission tomography (PET) radiopharmaceutical which is a cyclotron produced by a particles acceleration of beam with the [O-18](p,n). The structure of [F-18]Fluorodopa and its long half-life makes it suitable for transportation to centers with no cyclotron facility on site, allowing for more flexible imaging timings, and offers the possibility of late images, which are very important in some cases such as assessment of brain tumors and NETs.

According to an article by Luurtsema et al., to determine the specific activity, the radiochemical and chemical purity of [F-18]Fluorodopa a quality control analysis was done on High Performance Liquid Chromatography (HPLC) system and to improve the analysis they use Ultra Performance Liquid Chromatography (UPLC) with UV and an online radioactivity detector.

[F-18] Fluorodopa was at least stable >95 % radiochemical purity during 8 hour after synthesis. Aurélien et al. (2016) studied diagnosis and localization of persistent medullary thyroid carcinoma using [F-18] Fluorodopa in positron emission tomography/computed tomography (PET/CT) scan. The main purpose of this study was to describe the performance of [F-18] Fluorodopa in diagnosis of MTC. They did the study on 86 patients who had MTC with high levels of calcitonin after initial surgery with at least 6 months of follow-up after [F-18] Fluorodopa PET/CT scanning. All patients fasted for a minimum of 3 hours before being injected with [F-18] Fluorodopa. Early cervico-mediastinal image acquisition was started 10 min after injection [F-18] Fluorodopa. After that they followed it up by whole-body (WB) image acquisition started 30 minutes after injection from the top of the skull to the upper third of the femur. Serum calcitonin levels were measured at the time of the PET study and during the study. [F-18] Fluorodopa PET/CT was considered positive in 65 patients and negative in 21 patients and as a result of the study is that [F-18] Fluorodopa is a sensitive imaging tool that it can be used with PET/CT to enables early diagnosis of a significant number of patients with distant metastasis.

Another study that was done by Caobelli et al. (2017) to examined the predictive and prognostic value of [F-18] Fluorodopa PET/CT in patients affected by recurrent medullary carcinoma of the thyroid. This study was done on 60 patients with recurrent MTC. All patients underwent a restaging [F-18] Fluorodopa PET/CT, done at least 6 months after surgery. [F-18] Fluorodopa was injected intravenously, after one hour images were acquired from the vertex to the mid-thigh including the upper extremities. To perform non-uniform attenuation correction, a low-dose CT was acquired. [F-18] Fluorodopa showed abnormal findings in 27 patients and resulted unremarkable in 33 patients. The result of this study is that the [F-18] Fluorodopa PET/CT scan has an important prognostic value in predicting disease progression and mortality rate.

Another article talks about the difference between the diagnostic utility of PET/CT with [F-18] Fluorodopa and [F-18]FDG in persistent or recurrent medullary thyroid carcinoma. They did this study with 18 patients with recurrent MTC, identified by elevation of calcitonin or carcinoembryonic antigen (CEA). Each patient underwent a PET/CT with [F-18]FDG and then [F-18] Fluorodopa scan was performed. The time between two scans was between 5 to 80 days. From every patient a blood sample was taken to measure calcitonin and carcinoembryonic antigen (CEA) before administration of the radiopharmaceutical. Both radiopharmaceuticals were administered intravenous. The images were taken using a PET/CT hour after administration of the radiopharmaceutical. The scan were taken from the cranial vertex up to the middle third of the femoral diaphysis. 28 lesions were detected with [F-18] Fluorodopa versus 16 lesions with [F-18] FDG. In the patient analysis, [F-18] Fluorodopa had a sensitivity of 70% while the sensitivity of [F-18] FDG PET/CT was 50%. In the detecting and locating lesions in patients with recurrent MTC [F-18]Fluorodopa PET/CT appears to be better than [F-18]FDG PET/CT. This study tends to be especially useful in patients with negative results in other imaging modalities and Ct≥150 pg/mL or CEA≥5 ng/mL.

Lastly, Beuthien-Baumann et al. compared the different diagnostic impacts of PET with [F-18] FDG, [F-18] Fluorodopa and [F-18] OMFD in recurrent or metastatic medullary thyroid carcinoma. This study contains data from 15 patients with previously surgically treated MTC. The time period between surgery and current study varied between 6 months and 21 years. All patients had elevated calcitonin and/or CEA levels. PET imaging was performed. All studies were taken in 2D mode and reconstructed iteratively with segmented transmission. The preparation of [F-18] FDG imaging required the patients to fast for 6 hour at least. The acquisition started 1 hour post intravenous injection. For [F-18] Fluorodopa and [F-18] OMFD imaging, only food intake without protein was allowed. To block the decarboxylation in muscle and intestine, the patients received 100 mg carbidopa orally 1 hour before [F-18] Fluorodopa injection. The acquisition started 45 minutes post injection. All patients underwent [F-18] FDG PET and [F-18] Fluorodopa PET ten patients underwent [F-18] OMFD PET. With [F-18] FDG, seven patients showed foci in the neck, mediastinum, upper abdomen or bone. In seven patients, [F-18] Fluorodopa appeared suspicious foci; five of these seven patients showed partially corresponding uptake of [F-18] FDG in the neck and mediastinum. Two of these patients underwent surgery and metastases were proved. [F-18] FDG and 1[F-18] Fluorodopa showed foci that were highly suspicious for local recurrence or metastasis of MTC. Neuroendocrine uptake of [F-18] Fluorodopa seems to be more specific than [F-18]FDG uptake for the detection of 18 metastases of MTC. Uptake of the amino acid tracer [F-18] OMFD had no diagnostic impact in the ten patients investigated.

In conclusion, the main purpose of using F-18 Fluorodopa PET radiopharmaceutical is to detect medullary thyroid carcinoma.