Parathyroid

8.5.1 Radiopharmaceutic

• 2- [^99mTc]Tc-methoxyisobutylisonitrile ([^99mTc]Tc-sestamibi)
• Na[^99mTc]TcO₄ or Na[¹²³I]I for dual-tracer imaging.

8.5.2 Uptake mechanism / biology of the tracer

[^99mTc]Tc-sestamibi is a lipophilic cation that crosses the cell membrane and penetrates reversibly into the cytoplasm via thermodynamic driving forces and then irreversibly passes the mitochondrial membrane using a different electrical gradient regulated by a high negative inner membrane potential. The tumour cells, with their greater metabolic turn-over, are characterized by a higher electrical gradient of mitochondrial membrane, and thereby exhibit an increased accumulation of [^99mTc]Tc-sestamibi compared to normal cells.

Na[^99mTc]TcO₄ is taken up by thyroid tissue but not organified, so the image obtained can be used for subtraction from sestamibi or tetrofosmin images. The remaining activity may then represent a parathyroid adenoma.

Na[¹²³I]I is taken up by functioning thyroid tissue and organified. The organ to background ratio is higher than for Na[^99mTc]TcO₄.

8.5.3 Indications

Approved by the European Medicines Agency (EMA):

• Parathyroid Imaging: preoperative localization of hyperactive parathyroid(s) in patients with established primary hyperparathyroidism or tertiary hypothalamo-pituitary-thyroid (HPT) in nephropathic patients.
• Parathyroid scintigraphy should be performed in all patients undergoing first minimally invasive or unilateral neck exploration in pHPT and in all patients undergoing reoperation for persistent or recurrent pHPT3. Also, parathyroid scintigraphy may help to distinguish between patients who are suitable for minimally invasive surgery and those who require bilateral neck exploration. In sHPT (or tHPT), the lower sensitivity means the case for scintigraphy is not as strong and may depend on the surgeon’s preferences. If bilateral neck exploration is performed as primary operation, imaging may not contribute significantly as the lower sensitivity requires exploration of all parathyroid glands during surgery. Instead, an intraoperative PTH assay may help to determine the success of the operation. In case of reoperation, however, imaging may help to better guide the surgeon.

8.5.4 Contra-indications

• The only absolute contra-indication is pregnancy.
• For [^99mTc]Tc-sestamibi it is not recommended to interrupt breast feeding although an interruption of 4 h during which one meal is discarded can be advised to be on the safe side. Regarding Na[^99mTc]TcO₄, a 12-h interruption is recommended, and cessation is recommended following Na[¹²³I]I administration [3].

8.5.5 Clinical performances

Pooled detection rate of [^99mTc]Tc-sestamibi SPECT/CT in the preoperative planning of patients with PHPT is 88% (95% CI = 84% to 92%) and 88% (95% CI = 82% to 92%) on a per patient-based and per lesion-based analysis, respectively [150].

8.5.6 Activities to administer

The suggested activities to administer are

• [^99mTc]Tc-sestamibi: 500-700 MBq
• For dual tracer imaging, ^99mTc-sestaMIBI: 185-444 MBq and ¹²³I NaI: 7.5-22 MBq.

In paediatric nuclear medicine, the activities should be modified according to the EANM paediatric dosage card (https://www.eanm.org/publications/dosage-calculator/). The minimum recommended activity to administer is 80 MBq.

8.5.7 Dosimetry

The effective dose for [^99mTc]Tc-sestamibi is 9.0 µSv/MBq [3]. The organ with the highest absorbed dose are the kidneys: 36 µGy/MBq and the gallbladder wall: 39 µGy/MBq.
The effective dose for Na[¹²³I]I is 150 µSv/MBq (low uptake, iv administration) [3]. The organ with the highest absorbed dose is the thyroid: 2.7 mGy/MBq.
The range in effective dose for [^99mTc]Tc-sestamibi is 4.5-6.3 mSv per single procedure and 1.7-4.0 mSv for the dual tracer imaging procedure

Caveat:
“Effective Dose” is a protection quantity that provides a dose value related to the probability of health detriment to an adult reference person due to stochastic effects from exposure to low doses of ionizing radiation. It should not be used to quantify the radiation risk for a single individual associated with a particular nuclear medicine examination. It is used to characterize a certain examination in comparison to alternatives, but  it should be emphasized that if the actual risk to a certain patient population is to be assessed, it is mandatory to apply risk factors (per mSv) that are appropriate for the gender, the age distribution and the disease state of that population."

8.5.8.1 Image acquisition

A single-head gamma camera can be used for planar images which must include anterior views of the neck and the upper thorax in all cases. Early (10–15 min post-injection) and delayed (1.5–2.5 h post-injection) high count images are obtained. Additional

SPECT/CT provides fused images of functional and anatomical modalities which considerably improve the interpretation of findings of individual procedures.

8.5.8.2 Interpretation criteria/major pitfalls

Any extra-physiological focus of [^99mTc]Tc-sestamibi uptake in neck/mediastinum (planar/SPECT) is rated as positive. Corresponding nodule(s) in the CT part of SPECT/CT increases specificity. Subtraction analysis: any focus of [^99mTc]Tc-sestamibi uptake after subtraction is rated as positive.

Major Pitfalls are proliferating thyroid nodules.

8.5.9 Patient preparation

Discontinuation of thyrostatic drugs (thiamazol, methimazole or propylthiouracil) is recommended if dual isotope protocols are used, because thyrostatic medication could reduce uptake into the thyroid gland. Discontinuation for 3 days is sufficient, also for propylthiouracil. The same is true for iodine-containing contrast media for dual tracer imaging which should be avoided for at least 6 weeks.

When subtraction scintigraphy is to be performed in a patient on thyroid hormone replacement, this treatment should be withheld for 2-3 weeks before the investigation. Alternatively, one can use single-tracer sestamibi washout techniques.

No preparation for dual-phase [^99mTc]Tc-sestamibi.

8.5.10 Methods

The detailed recommendations are available in the 2009 EANM parathyoid guidelines  [151].