Parathyroid Imaging with Tc-99m- MIBI

Luis E. Diaz, M.D.

Kevin Donohoe, M.D.

May 3, 1994

Case Presentation:

A 53 year old female had an incidental finding of hypercalcemia. A diagnosis of primary hyperparathyroidism was made and localization of a parathyroid adenoma responsible for the increased parathormone was desired.

Imaging

Parathyroid scan (23k bytes) with 20 mCi of Tc-99-m Sestamibi.

Protocol

Anterior cervicothoracic images were obtained with a large field of view camera equipped with a low-energy, high resolution, parallel hole collimator at 20 minutes (shown on left). Repeat set of images were obtained at two hours post-injection (shown on right). Both initial and delayed images were obtained for ten minutes each.

Findings:

Initial images showed a focal area of increased tracer uptake adjacent to the medial aspect of the lower pole of the right thyroid lobe (arrow, 23k bytes). Delayed images showed persistent activity in the same region. Impression was of a parathyroid adenoma in the lower pole of the right thyroid lobe.

Neck exploration and pathology:

A 2x1x0.5 cm mass of tan/pink tissue weighing 1.1 gm consistent with a right inferior parathyroid adenoma.

Discussion:

Parathyroid scintigraphy is based on the concept of physiologic localization in tissue using metabolic markers. Cobalt-57 vitamin B12, Se-75-methionine and Ce-131-chloride have been successively used for parathyroid imaging. Dual isotope scintigraphy with Thallium-201 (Tl-201) and Technetium-99m (Tc-99m) pertechnetate has been the standard imaging technique since first descried by Ferlin in 1983. This technique was then modified by Winzelberg in 1985. Thallium/pertechnetate imaging is based on differential localization of tracer. Thallium localizes in both thyroid and parathyroid tissues, whereas pertechnetate localizes only in thyroid tissue. A discordant pattern of excess Thallium as compared to pertechnetate is therefore suggests parathyroid enlargement.

Published data show marked variability of Thallium/pertechnetate scintigraphy results. Regrouping 14 studies by Hauty et al. with a total of 317 patients, the accumulated sensitivity to detect parathyroid adenomas was 82%. The diagnostic accuracy was 78%, the positive predictive value 94% and the false positive rate was 5%.

Although dual isotope parathyroid scintigraphy has shown satisfactory results, it suffers from technical limitations and interpretative pitfalls. These include: unfavorable Tl-201 dosimetry, 80 keV photons of thallium, poor quality images, rigorous technique, prolonged patient immobilization and poor thyroid uptake of pertechnetate due to interfering medication or recent iodinated contrast media. Improved parathyroid scintigraphy has been reported with Tc-99m Sestamibi.

Tc-99m Sestamibi offers several technical and interpretative advantages over Thallium. Like Thallium, MIBI accumulates in both the thyroid and parathyroid glands with a peak activity at 4-6 minutes after injection. Both tracers "wash out" from the thyroid gland quickly; yet unlike Thallium, MIBI is retained in abnormal parathyroid, facilitating visualization.

The mean uptake of Thallium is greater than that of MIBI in hyperplastic, adenomatous parathyroid and thyroid tissue. There is however no difference in uptake of Thallium between parathyroid adenoma and thyroid tissue, whereas there is a clear difference in uptake of MIBI in these tissues. This difference would facilitate visualization of pathology due to a higher target to background ratio. The literature suggests that the maximum difference between MIBI uptake in the thyroid and the parathyroid occurs between 15-28 min.

The degree of MIBI avidity by the parathyroid adenoma is independent of PTH levels, but depends, in part, on gland size. The smallest reported pathologic gland weighed 150 mg; the largest weighed 8 gm. For yet unclear reasons, large (2 gm) adenomas may not accumulate sufficient MIBI for detection. The mechanism of MIBI localization in adenomas is not entirely clear. Chiu et al. have suggested that Tc-99m-MIBI is sequestered within the cytoplasm and mitochondria in response to electrical potentials generated across the membrane bilayers of both the cell and the mitochondria. This suggests that a tissue with a large number of mitochondria (e.g. myocardial cell) may take up MIBI more avidly and retain the tracer longer. Recently, Sandrock et al. showed that the parathyroid adenomas had a large number of mitochondria per cell.

To date approximately 450 patients with hyperparathyroidism have been studied with Sestamibi. The sensitivity ranges from 88-100%. In studies comparing MIBI to Tl-201, MIBI has either shown a parathyroid adenoma more convincingly or localized one that was missed with Tl-201. No a single adenoma positive with Tl-201 and negative with MIBI has been reported.

Conclusions:

Tc-99m Sestamibi is a promising radiopharmaceutical for the detection and localization of parathyroid adenomas in patients with primary hyperparathyroidism. More data is needed regarding uptake, wash out, optimal dose and mechanism of uptake, to improve parathyroid scintigraphy with MIBI.

References:

1. O'Doherty M, Kettle AG, Wells P, CollinsR, Coakley AJ. Parathyroid Imaging with Technetium- 99m Sestamibi: Preoperative Localization and Tissue Uptake Studies. JNM 1992; 33: 313-318.

2. Taillefer R, Boucher Y, Potvin C, Lambert R. Detection and Localization of Parathyroid Adenomas in Patients with Hyperparathyroidism Using a Single Radionuclide Imaging Procedure with Technetium-99m-Sestamibi (Double-Phase Study). JNM 1992; 33: 1801-1809.

3. Oates Elizabeth. Improved parathyroid scintigraphy with Tc-99m MIBI a superior radiotracer. App Rad 1994: 37-40.

4. Chiu ML, Kronauge JF and Piwnica-Worms D. Effect of Mitochondrial and Plasma Membrane Potentials on Accumulation of Hexakis (2-Methoxyisobutylisonitrile) Technetium in Cultured Mouse Fibroblasts. JNM 1990; 31:1646-1653.

5. Goris ML, Basso LV, Keeling C. Parathyroid Imaging. JNM 1991; 32: 887-889.

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J. Anthony Parker, MD PhD, Tony_Parker@bih.harvard.edu