Incidental Detection of Thyroid Neoplasm on 99mTc-SestaMIBI Myocardial Perfusion Scan-A Novel Tumour Tracer Revisted

We report a case of a young Indian male who had an incidental abnormal focal uptake of 99mTechnetium-MIBI (Methoxy Isobutyl Isonitrile) in the right lobe of thyroid while undergoing 99mTc-MIBI myocardial perfusion gated SPECT (Single Photon Emission Computed Tomography) imaging as a part of his myocardial ischemia status evaluation. This focal uptake was eventually detected to be a malignant thyroid nodule for which he underwent total thyroidectomy. His biopsy was reported as Hurthe cell nodule. Though incidental detection of thyroid, breast and lung malignant pathology on 99mTcMIBI myocardial perfusion scans is well known, this case is a reminder and exemplifies the potential of 99mTc-MIBI not only as an excellent myocardial perfusion agent but also as a non specific tumour tracer (for its larger usage as a tracer for neoplastic survey).


Introduction
Incidental finding of thyroid nodule(s) during various anatomical imaging procedures like USG, CT and MRI scan is relatively common. However, identification of such unsuspected thyroid nodule in functional imaging techniques like whole body PET CT or other conventional nuclear medicine scans have added benefit because of their physiological basis. Various radiopharmaceuticals have been seen to detect incidental thyroid nodules. 99m Tc-MIBI has been used in characterization of cold nodules in thyroid especially where FNAC is negative [1] and also in detecting recurrent Medullary Thyroid Carcinoma in patients with calcitonin values in excess of 6000 ng/liter .

Case Report
This 42 year old, Indian male patient with no known major illnesses had presented for an annual health checkup which included a cardiac work up as well. During his cardiac evaluation, he underwent a 99m Tc-MIBI stress myocardial perfusion scan following abnormal ECG findings on tread mill test.
10 mCi (millicurie) of 99m Tc-MIBI was administered intravenously at the height of exercise on a treadmill and a planar immediate post stress thorax imaging was acquired on Siemens Symbia E Gamma Camera that is routinely done as a quality control measure (for radiotracer labeling) and also to look for early sign of LV dysfunction.
Myocardial Gated SPECT (Single Photon emission Computed Tomography) imaging is done after a delay of 45-60 minutes post injection and patients are encouraged to have a fatty meal to ensure better gall bladder clearance.
A usual practice is to acquire an immediate anterior thorax planar image to check the quality of 99m Tc-MIBI preparation as well to document any associated LV (left ventricular) dysfunction and abnormal non-cardiac 99m Tc-MIBI tracer uptake.
In this patient, post stress planar anterior thorax image showed an incidental focal 99m Tc-MIBI uptake in right lobe of thyroid that showed significant tracer retention in 2 hours delayed image (on region ratio calculation). Thus raising the suspicion of a thyroid neoplasm. His rest SPECT myocardial perfusion scan was done 3 hours later with 30 mCi of 99m Tc-MIBI.
A delayed anterior neck image acquired after 2 hours of injection showed focal retention of radiopharmaceutical (Figures 1 and 2). On subsequent physical examination, the thyroid gland was found to be minimally enlarged with no palpable nodules (Figures 3).
His 99m Tc-MIBI myocardial perfusion scan was negative for myocardial ischemia (Figure 4). USG guided FNAC was suggested in view of the 99m Tc-MIBI concentration right thyroid gland with no palpable abnormality.
USG neck showed an isoechoic nodule with abundant intralesional vascularity and calcifications in the right thyroid lobe. Multiple subcentimetric bilateral level II, III cervical lymph nodes were also seen with nodes on right side showing loss of fatty hilum, largest node measured 1.6 × 0.5 cm in size.
FNAC from the right thyroid nodule showed moderate cellularity and was inconclusive to rule out an occult malignancy (Figures 3). Patient subsequently underwent total thyroidectomy and his histopathology was reported as Hurthle cell nodule.    .45 x zoom, both detectors, 37 views, detector configuration 76 degree, non-circular orbit, step and shoot mode acquisition) rom apex to base of the heart showing nor-mal perfusion in all segments of the left ventricular myocardium with no evidence of ischemia. Stress gated images were acquired after 45 min of 99m Tc-MIBI injection at peak exercise (after the patient had achieved >85% target heart rate and double product of >25,000).Rest gated images were acquired after 45 min of reinjection of 30 mCi 99m Tc-MIBI at rest. 99m Tc-MIBI is a lipophilic cationic organometallic complex composed of one atom of Technetium Tc (I) and six ligand molecules of 2-methoxy isobutyl isonitrile (MIBIN) [2]. A critical property of myocardial perfusion agents like MIBI is its uptake being directly proportional to regional blood flow. Its tumour seeking property is based on its ability to get concentrated intracellularly in actively dividing cells, i.e mitochondrial complex [3]. 99m Tc-MIBI sequestered within mitochondria by the large negative transmembrane potentials [4]. Accordingly, more intense MIBI concentrations have been found in malignant tumor cells than in normal cells because of the higher electrical gradient of the former. The mechanism of cellular radiopharmaceutical accumulation has been reported to depend on the size of a tumor, the blood flow within it [5], and the richness of mitochondria in the tumor cells [5,6]. 99m Tc-MIBI uptake is documented to detect differentiated thyroid carcinoma nodal metastatic spread, breast malignancies, lung malignancies, brain tumors, sarcomas etc. [7] and also medullary carcinoma thyroid [1]. 99m Tc-MIBI scanning was even found to be more sensitive than CT for localizing soft-tissue metastatic disease [8]. Also, once inside the cell, 99m Tc-MIBI becomes a substrate for P-glycoprotein which mediates its excretion from the cell. Hence, it can also act as a surrogate for a range of chemotherapeutic agents and this may be used to predict tumour response to chemotherapy as the level of 99m Tc-MIBI uptake appears to be inversely dependent on the P-glycoprotein expression of the tumour [9].

Conclusion
This incidental finding highlights the inherent tumour avidity of 99m Tc-MIBI which has been underutilised in general as a non-specific tumour detecting agent and also reflects the potential for thyroid nodule evaluation especially of those with high clinical suspicion but with equivocal or FNAC negative results.