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Doctoral dissertation

The role of 18F-choline PET/CT in the diagnosis of primary hyperparathyroidism

Author(s): Sebastijan Rep (Author), Marko Hočevar (Supervisor), Janja Vaupotič (Co-Supervisor), Luka Ležaič (Co-Supervisor)

Thesis defense date: 19.10.2018

Organization: MPŠ - Mednarodna podiplomska šola Jožefa Stefana

PID: 20.500.12556/ReVIS-14770

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Abstract

Primary hyperparathyroidism is an endocrine disorder that develops as a result of increased and uncontrolled formation and secretion of parathyroid hormone from the hyperfunctioning parathyroid glands. The pathologic process that gives rise to the disorder can be a parathyroid adenoma, a parathyroid hyperplasia and very rarely a parathyroid carcinoma. Hyperfunctioning parathyroid glands are usually localized with functional nuclear medicine imaging techniques using different protocols: a planar imaging in two stages, the subtraction scintigraphy or hybrid SPECT / CT. These imaging methods are based on different accumulation and distribution of radiopharmaceutical 99mTc-MIBI in hyperfunctional parathyroid glands and in the adjacent tissues.In recent years a new radiopharmaceutical 18F-cholin and PET/CT imaging technology has been increasingly used.
There were more research objectives: (1) to analyse the use of the 2 mm and 4 mm voxel size in the PET/CT protocol; (2) to evaluate the diagnostic performance of the preoperative localization of hyperfunctioning parathyroid glands in early, delayed and combined PET/CT, SPECT/CT protocol and subtraction scintigraphy in patients with biochemically proven primary hyperparathyroidism; (3) to determine if the size of hyperfunctioning parathyroid glands, serum parathormone, calcium and phosphate correlate with successful localization; and (4) to evaluate the quantity of radiation exposure of patients where early or combined PET/CT, SPECT/CT protocol and subtraction scintigraphy were performed.
For the preclinical analysis we used the NEMA phantom with six fillable spheres. The spheres and background was filled with a solution of 18F-choline, in ratio of 5:1. For clinical analysis we included 40 patients with biochemically proven primary hyperparathyroidism. In all patients we performed dual-phase 18F-choline PET/CT, SPECT/CT protocol and subtraction scintigraphy. For the preclinical and clinical part, identical reconstructions and quantitative values were used and contrast-to-noise ratio (CNRmax/mean) and contrast recovery coefficient (CRCmax/mean), and also a qualitative analysis (lesion presence/absence) was performed. For all imaging diagnostic methods we calculated sensitivity, specificity, positive and negative predictive value and accuracy. Also the correlation between the results of scintigraphic methods and the size of hyperfunctional parathyroid glands, serum calcium, phosphate and parathormone were calculated. To calculate the radiation exposure of patients, we used an ImPACT CT Patient Dosimetry Calculator and weights factors for radiopharmaceuticals (18F-choline, 99mTc-MIBI & 99mTc-pertechnetate).
When comparing NEMA phantom reconstructions with 4 mm and 2 mm voxel size, the contrast-to-noise ratio (CNRmax/mean), contrast recovery coefficient (CRCmax/mean) increases, particularly for small lesions (diameter ˂ 1.3 cm). Similar results were obtained in the analysis of 40 patients. The median volume of hyperfunctional parathyroid glands was 0,45 (0,07; 10,98) ml. The difference between average SUV (mean and max), CNR (mean and max) and CRC (mean and max) when using the 2 mm and 4 mm voxel size were statistically significant (P < 0.001) in both imaging phases. After visual analysis, the agreement between two physicians was high (p = 0.91). Using the 4 mm voxel size the sensitivity of PET/CT protocol decreased by 9 % in the first and 6 % in the second phase in comparison to 2 mm voxel size. Sensitivity and specificity were 40.0 % and 99.1 % for subtraction scintigraphy, 57.8 % and 99.1 % for combined early and delayed SPECT/CT protocol and 95.55 % and 99.1 % for combined early and delayed PET/CT protocol. We detected in our study that only the size of hyperfunctioning parathyroid glands correlated with the successful localization in image diagnostic methods. The median effective dose for the patient was 7.35 (6.56; 8.24) mSv after subtraction scintigraphy, which was statistically significantly higher than in combined early and delayed SPECT/CT protocol 6.68 (5.94; 8.04) mSv and in combined early and delayed PET/CT 2.77 (2.29; 3.77) mSv. The most sensitive and most accurate method of preoperative localization of hyperfunctioning parathyroid glands in patients with primary hyperparathyroidism is PET/CT. Only the size of hyperfunctioning parathyroid glands is associated with successful localization. The highest radiation exposure of patients is after subtraction scintigraphy.

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