**4. Parathyrod scintigraphy**

Historically, the success of scintigraphy had been compromised by the failure of finding a pharmaceutical agent with specific topic accumulation in parathyroid glands and their close proximity to the thyroid gland. That is why to find a reliable method to differentiate both glands on scintigraphy was crucial. This was first achieved by a combined use of two radionuclides with different uptake in the thyroid and parathyroid cells. The latter allowed to perform a subtraction of the obtained images of both glands and to visualize only the abnormal parathyroid gland, but this proved to be time consuming and with greate radiation exposure to the patients. The first widely used radionuclide for detecting hyperfunctioning parathyroid glands during the 80s was 201Thallium chloride (201Tl). 201Tl chloride accumulates equally in thyroid and parathyroid cells. To make differentiation possible, its application was followed by an injection of 99mTc pertechnetate, with predominant thyroid uptake. Then 99mTc pertechnetate thyroid images were digitally subtracted from the images obtained with 201Tl chloride to allow visualization only of the parathyroid glands [16].

Introduced in clinical practice by Coakley et al. [17], the 99mTc-sestamibi scintigraphy significantly increased the role of preoperative scintigraphy in patients with hyperparathyroidism. Firstly used as a cardiotropic agent this radionuclide showed increased accumulation in a variety of benign and malignant tumors. 99mTc-sestamibi consists of lipophilic cationic molecules. After being intravenously injected these molecules distribute throughout the body accordingly to the local blood supply and by passive diffusion through cell's membrane accumulate intracellularly into the mitochondria [18, 19]. Normally 99mTc-sestamibi distributes in parotid and submandibular salivary glands, thyroid gland, the heart and the liver, but not in normal parathyroid glands. Visualization of parathyroid adenomas and hyperplastic parathyroid glands depends on the presence of oxyphillic cells, which are rich of mitochondria. The cells of parathyroid adenomas have plenty of

mitochondria [20], while the normal parathyroid cells do not [21]. The highest rates of uptake of 99mTc-sestamibi are seen in the solitary adenomas of the parathyroid glands [22]. Not only the amount of intracellular mitochondria is important but also the quantity of oxyphillic cells in the tumors. If the percentage of oxyphillic cells exceeded 25%, accumulation of 99mTc-sestamibi was observed in 78% of parathyroid adenomas. Also false negative results are possible if the oxyphillic cells do not content sufficient amount of mitochondria [23]. Accumulation of 99mTc-sestamibi into the cells also can be influenced by their metabolic activity, the weight and the size of the tumor. This new radionuclide rapidly replaced 201Tl chloride because it showed better quality of the images and higher sensitivity for detecting abnormal parathyroid glands, with less radiation exposure [24].

99mTc-tetrofosmin another myocardial perfusion agent was also used for visualizing parathyroid glands in scintigraphy, but the data for its use so far are limited. 99mTc-tetrofosmin shows some similarities with 99mTc-sestamibi although the way of accumulation is different and it is retained mainly in the cytosol rather than in the mitochondria of the target cells. When used for parathyroid scintigraphy 99mTc-tetrofosmin shows slower washout from the thyroid gland, which makes it unsuitable for single-isotope dual-phase scintigraphy [25]. Nevertheless its sensitivity increases when used in combination with SPECT. Several studies [26, 27] of the diagnostic value of 99mTc-tetrofosmin scintigraphy for topic localization of the hyperfunctioning parathyroid glands in patients with PHPT, showed that this method was useful for the clinical practice and that the accumulation of 99mTc-tetrofosmin depends on the weight of the tumor and the level of PTH.

### **4.1 Protocols for nuclear medicine examination of parathyroid glands**

Generally three protocols are most widely used: single-phase dual-isotope subtraction, dual-phase single-isotope and combination of both [28].

In single-phase dual-isotope modality two types of radiopharmaceuticals with different organ uptake are used. One isotope (99mTc-sestamibi or 99mTc-tetrofosmin) with equal thyroid and parathyroid glands accumulation and another (123I or 99mTc-pertechnetate) with predominant uptake in the thyroid gland are applied consecutively. The obtained images are digitally subtracted and if there is a residual radionuclide accumulation on the subtracted images a hyperfunctioning parathyroid gland can be suspected [28]. Disadvantages of this method are the use of two radionuclides, the necessity of full collaboration from the patient's side to stay calm and motionless during the examination and the need of very precise positioning of the patient. In addition there is an increase possibility for the presence of artifacts on the subtracted images [29, 30].

The rationale of the single-isotope protocol is based upon the different washout periods of the radionuclide from the thyroid and parathyroid glands. In this method, after an injection of a single radionuclide, early (at 10–15 min) and late (at 1.5–3 h) images are obtained [28].

There are a very few studies directly comparing the results from single-isotope dual-phase modality with single-phase dual-isotope subtractional scintigraphy and the results are inconclusive [31, 32]. So far there is no clear confirmed advantages of one type over another.

#### *4.1.1 Preparation of the patient*

No preliminary preparation of the patients before performing single isotope dual-phase scintigraphy is necessary. In subtractional modality some preliminary conditions should be followed such as: discontinuation of Levothyroxine or Iodine

**49**

*Parathyroid Scintigraphy*

*4.1.2 Radiopharmaceuticals*

to 1110 MBq (20–30 mCi).

**99mTc-tetrofosmin**

negative results [34, 35].

changed glands [40, 41].

(2–10 mCi).

*DOI: http://dx.doi.org/10.5772/intechopen.90341*

homeostasis, and family history should be taken.

containing drugs minimum 20 days before the examination. A case history of every patient about the duration of the disease, any concomitant diseases and medications, especially drugs that could possibly interfere with the calcium-phosphate

99mTc-sestamibi and 99mTc-tetrofosmin: they are applied intravenously from 740

99mTc-pertechnetate has a half-life of 6 h and possesses energy of 140 keV. It is used for visualization of the thyroid gland because it accumulates in a functioning thyroid cells. Intravenously 99mTc-pertechnetate is applied form 74–350 MBq

99mTc-sestamibi accumulates in the thyroid and parathyroid glands, but the washout time from both glands differs, showing faster disappearing from the thyroid and retention in parathyroid cells. This allows successful visualization of pathologically changed parathyroid glands on the obtained later images—1.5–2 h after the injection of the radionuclide. This different retention time in both glands may be related to some down-regulation of the P-glycoprotein system in parathyroid adenomas, which delays washout of the nuclide [33]. Just the opposite, in parathyroid hyperplasia these so-called multidrug-related resistance molecules can be upregulated and can cause faster washout of 99mTc-sestamibi and lead to false

To avoid this disadvantage and to improve sensitivity and specificity, the use of single-isotope dual phase (early and late) scintigraphy, based upon the suggestion that 99mTc-sestamibi is washed out faster from the thyroid gland than from the hyperfunctioning parathyroid cells, is recommended [36]. This single-isotope dual phase scintigraphy gained popularity due to its convenience. The fact that 99mTc-sestamibi can also be accumulated in solitary thyroid nodules diminishes the specificity of this procedure, especially in areas with higher incidence of nodular goiter [37, 38]. Some parathyroid adenomas also show rapid washout of 99mTcsestamibi and make their visualization difficult by this procedure [39]. This led to an introduction of a modified protocol for subtractional scintigraphy by adding a second radionuclide with a preferential accumulation in the thyroid tissue. 99mTc-sestamibi scintigraphy is generally regarded to be the most sensitive and specific imaging modality especially when it is combined with other imaging procedures. The combination of US examination with dual-isotope 99mTc pertechnetate/99mTc-sestamibi scintigraphy for preoperative localization of parathyroid adenomas leads to visualizing of the parathyroid adenomas in 95.2% of the cases (20 patients out of 21). Reaching such high diagnostic precision allows to minimize the extent of the surgical procedure and gives way to apply routinely and successfully minimally invasive parathyroidectomy only of the pathologically

Comparing different imaging methods,99mTc-sestamibi scintigraphy has higher sensitivity and specificity than US and CT in discovering adenomas of the parathyroid glands. With regards to the hyperplasia of the parathyroid glands 99mTc-sestamibi scintigraphy shows to be of less value [42, 43]. Hyperplastic parathyroid glands

**4.2 Single-isotope dual-phase scintigraphy with 99mTc-sestamibi and** 

*4.2.1 Single-isotope dual-phase scintigraphy with 99mTc-sestamibi*

containing drugs minimum 20 days before the examination. A case history of every patient about the duration of the disease, any concomitant diseases and medications, especially drugs that could possibly interfere with the calcium-phosphate homeostasis, and family history should be taken.
