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

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 negative results [34, 35].

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 changed glands [40, 41].

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 are visualized in 10–62.5% of the cases [44, 45]. In multiple endocrine neoplasia syndrome (MEN), where hyperplasia of the parathyroid glands is common, only 55% of the abnormal glands are seen on 99mTc-sestamibi scintigraphy [42, 46, 47]. 99mTcsestamibi scintigraphy shows to be highly effective in discovering ectopic hyperfunctioning parathyroid glands, which in some studies, are observed in approximately 20% of the cases with PHPT and represent a diagnostic and therapeutic challenge [48]. Visualizing small parathyroid adenomas represents a specific problem. One study showed, that in surgically removed adenomas weighted less than 0.5 g, preoperative US was negative, but 99mTc-sestamibi scintigraphy discovered adenomas in 87% of cases and the combination with SPECT increased sensitivity to 95% [21].

In patients with SHPT, seems to have a direct correlation between 99mTcsestamibi uptake with the blood level of parathyroid hormone and the phase of the cells' cycles [49]. The lowest level of accumulation corresponds to G(0) phase and the highest to phase G(2) + S. No such correlation with the weight of the glands is found [49]. The fixation of the radionuclide depends on the functional status of the tissues, i.e., increased accumulation accompanies the cells' active growing phase or is directly connected to the state of autonomy of the parathyroid cells [46].

The reason why not all pathologically changed parathyroid glands accumulate radionuclide remains unclear. This may be due to the different degree of activity and proliferation of the cells of the parathyroid adenomas. It was suggested that there is a relationship between nuclide accumulation and the degree of autonomy of the cells of the adenoma, i.e., the loss of the suppressive effect of calcium upon the secretion of the parathyroid hormone. The cells of the parathyroid adenomas and these of the hyperplastic glands show higher threshold for calcium suppression or have no threshold at all in comparison with the normal parathyroid cells. Due to this fact, these cells secrete more PTH for any given blood calcium level, show higher metabolic rate and capability to accumulate more 99mTc-sestamibi. Hyperplastic parathyroid glands are to some extent with preserved functional regulation, respond to the normal suppressive stimuluses, have lower metabolic rate and accumulate less of the radionuclide.

Due to its higher affinity to the parathyroid adenomas, 99mTc-sestamibi scintigraphy was used in cases of relapse of the hyperparathyroidism after parathyroidectomy or after autotransplantation of parathyroid glands.

Nowadays, there are several imaging methods for discovering hyperplastic parathyroid glands. The results so far are inconclusive. The dual-phase 99mTcsestamibi scintigraphy in preoperative localization of the hyperplastic parathyroid glands in patients with profound secondary hyperparathyroidism do not show high sensitivity, but is of help to discriminate between patients with nodular and diffuse hyperplasia [50].

The role of 99mTc-sestamibi scintigraphy in patients with end-stage renal disease and secondary hyperparathyroidism is still unclear. The uptake of 99mTc-sestamibi can be suppressed by the use of calcitriol in these patients. In one study [51] 99mTcsestamibi scintigraphy managed to visualize 1 or more (maximum 3) parathyroid glands in most, but not in all patients on hemodialysis with PHT levels above 600 pg/ml. Performing suppressive test with calcitriol (2 mg of calcitriol applied i.v. after each hemodialysis for two consecutive weeks) showed suppression of 99mTcsestamibi uptake at least in one parathyroid gland in 57% of the cases and full suppression in all glands in 36%. The basal level of PHT or its lowering after this test showed to be of no predictive value for the suppression of 99mTc-sestamibi uptake in the parathyroid glands. Because of its lower sensitivity, the 99mTc-sestamibi scintigraphy was found to be of limited value in preoperative evaluation in uremic patients with secondary hyperparathyroidism, but its significance grew up in localizing hyperfunctioning glands left after the first operation [51].

**51**

**Figure 2.**

*parathyroid gland.*

*Parathyroid Scintigraphy*

**Figure 1.**

*parathyroid gland.*

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

Single-isotope dual phase 99mTc-sestamibi scintigraphy is easily performed, and needs only application of 99mTc-sestamibi. After injection of the radiopharmaceutical, early (10–15 min), and late planar (1,5–3 h) images are obtained (**Figures 1** and **2**).

*Single-isotope dual-phase scintigraphy with 99mTc-sestamibi. The late image (120 min) shows a focus of a residual activity (arrow), caudally of the right thyroid lobe consistent with adenoma of the right lower* 

*Single-isotope dual-phase scintigraphy with 99mTc-sestamibi. On the early images (20 min) relatively diffuse uptake in the area of the thyroid gland and a focus of increased accumulation of the radionuclide (thin arrow), caudally of the left thyroid lobe are seen. On the late phase images (120 min) only a focus of a residual activity (thick arrow), caudally of the left thyroid lobe is visualized-suggesting adenoma of the lower left* 

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

Single-isotope dual phase 99mTc-sestamibi scintigraphy is easily performed, and needs only application of 99mTc-sestamibi. After injection of the radiopharmaceutical, early (10–15 min), and late planar (1,5–3 h) images are obtained (**Figures 1** and **2**).

#### **Figure 1.**

*Medical Isotopes*

are visualized in 10–62.5% of the cases [44, 45]. In multiple endocrine neoplasia syndrome (MEN), where hyperplasia of the parathyroid glands is common, only 55% of the abnormal glands are seen on 99mTc-sestamibi scintigraphy [42, 46, 47]. 99mTcsestamibi scintigraphy shows to be highly effective in discovering ectopic hyperfunctioning parathyroid glands, which in some studies, are observed in approximately 20% of the cases with PHPT and represent a diagnostic and therapeutic challenge [48]. Visualizing small parathyroid adenomas represents a specific problem. One study showed, that in surgically removed adenomas weighted less than 0.5 g, preoperative US was negative, but 99mTc-sestamibi scintigraphy discovered adenomas in 87% of cases and the combination with SPECT increased sensitivity to 95% [21]. In patients with SHPT, seems to have a direct correlation between 99mTcsestamibi uptake with the blood level of parathyroid hormone and the phase of the cells' cycles [49]. The lowest level of accumulation corresponds to G(0) phase and the highest to phase G(2) + S. No such correlation with the weight of the glands is found [49]. The fixation of the radionuclide depends on the functional status of the tissues, i.e., increased accumulation accompanies the cells' active growing phase or

is directly connected to the state of autonomy of the parathyroid cells [46].

and accumulate less of the radionuclide.

hyperplasia [50].

tomy or after autotransplantation of parathyroid glands.

hyperfunctioning glands left after the first operation [51].

The reason why not all pathologically changed parathyroid glands accumulate radionuclide remains unclear. This may be due to the different degree of activity and proliferation of the cells of the parathyroid adenomas. It was suggested that there is a relationship between nuclide accumulation and the degree of autonomy of the cells of the adenoma, i.e., the loss of the suppressive effect of calcium upon the secretion of the parathyroid hormone. The cells of the parathyroid adenomas and these of the hyperplastic glands show higher threshold for calcium suppression or have no threshold at all in comparison with the normal parathyroid cells. Due to this fact, these cells secrete more PTH for any given blood calcium level, show higher metabolic rate and capability to accumulate more 99mTc-sestamibi. Hyperplastic parathyroid glands are to some extent with preserved functional regulation, respond to the normal suppressive stimuluses, have lower metabolic rate

Due to its higher affinity to the parathyroid adenomas, 99mTc-sestamibi scintigraphy was used in cases of relapse of the hyperparathyroidism after parathyroidec-

The role of 99mTc-sestamibi scintigraphy in patients with end-stage renal disease and secondary hyperparathyroidism is still unclear. The uptake of 99mTc-sestamibi can be suppressed by the use of calcitriol in these patients. In one study [51] 99mTcsestamibi scintigraphy managed to visualize 1 or more (maximum 3) parathyroid glands in most, but not in all patients on hemodialysis with PHT levels above 600 pg/ml. Performing suppressive test with calcitriol (2 mg of calcitriol applied i.v. after each hemodialysis for two consecutive weeks) showed suppression of 99mTcsestamibi uptake at least in one parathyroid gland in 57% of the cases and full suppression in all glands in 36%. The basal level of PHT or its lowering after this test showed to be of no predictive value for the suppression of 99mTc-sestamibi uptake in the parathyroid glands. Because of its lower sensitivity, the 99mTc-sestamibi scintigraphy was found to be of limited value in preoperative evaluation in uremic patients with secondary hyperparathyroidism, but its significance grew up in localizing

Nowadays, there are several imaging methods for discovering hyperplastic parathyroid glands. The results so far are inconclusive. The dual-phase 99mTcsestamibi scintigraphy in preoperative localization of the hyperplastic parathyroid glands in patients with profound secondary hyperparathyroidism do not show high sensitivity, but is of help to discriminate between patients with nodular and diffuse

**50**

*Single-isotope dual-phase scintigraphy with 99mTc-sestamibi. The late image (120 min) shows a focus of a residual activity (arrow), caudally of the right thyroid lobe consistent with adenoma of the right lower parathyroid gland.*

#### **Figure 2.**

*Single-isotope dual-phase scintigraphy with 99mTc-sestamibi. On the early images (20 min) relatively diffuse uptake in the area of the thyroid gland and a focus of increased accumulation of the radionuclide (thin arrow), caudally of the left thyroid lobe are seen. On the late phase images (120 min) only a focus of a residual activity (thick arrow), caudally of the left thyroid lobe is visualized-suggesting adenoma of the lower left parathyroid gland.*

#### *Medical Isotopes*

In some cases, the obtained early and late images show no signs of abnormal accumulation of radionuclide, but when combined with SPECT, than adenomas located at the back of the thyroid gland become visible (**Figure 3a** and **b**).

So, the combination of a single-isotope dual-phase scintigraphy with 99mTcsestamibi with SPECT can be of great help.

During many years in the past, two-dimensional images have been obtained, mainly AP-images, and rarely this was combined with lateral and oblique images [52, 53].

SPECT has gained more importance, because it gives three-dimensional images. There are accumulating data from the literature, that it improves sensitivity for discovering and localizing the hyperfunctioning parathyroid glands [54, 55]. The main reason for this is the improved contrast resolution of SPECT (**Figure 4**).
