New use for an old isotope

Objectives: Differentiated thyroid cancer (DTC) patients with elevated or rising serum thyroglobulin (Tg) levels and multiple other negative conventional imaging studies represent a clinically difficult group of patients. ^99m Tc-sestamibi is a non-conventional imaging study for DTC that was used in the 1980s-1990s to help evaluate DTC patients before being replaced with ¹⁸F-FDG. However, 18F-FDG PET scans may also be negative in these patients. This is a preliminary analysis of our study to evaluate the diagnostic use of ^99mTc-sestamibi scans to identify the source of elevated or rising Tgs in patients with negative conventional imaging including negative 18F-FDG PET scans. Methods This prospective study included DTC patients who were at least 18 years old, had at least one prior ¹³¹I therapy, and had elevated Tg>5 ng/ml or positive anti-Tg antibodies (TgAb). In addition, all of the following imaging studies must have been clinically reported as negative for recurrence or metastasis within the last 12 months: neck ultrasound, diagnostic radioiodine scan, chest x-ray, CT of the chest/abdomen with/without contrast, and ¹⁸F-FDG PET/CT. If other imaging studies were performed, such as bone scans or brain imaging, these must also have been read as negative. This study was approved by the IRB at MedStar Health and all participants signed informed consent. Participants were injected with 925 MBq (25 mCi) of ^99mTc-sestamibi intravenously and whole body images were acquired after ~1h with acquisition speed 4cm/min with parallel-hole low-energy collimator. Extra spot view, pinhole view, or SPECT/CT images were performed when necessary. Two blinded nuclear medicine physicians independently interpreted the ^99mTc-sestamibi images, and graded each foci 1-5 (1 = definite physiological uptake or artifact; 2 = most likely physiological uptake or artifact; 3 = indeterminate; 4 = most likely recurrence or metastasis; 5 = definite recurrence or metastasis). Discordant findings were resolved by consensus. Foci graded 3-5 were categorized as positive result and was followed-up for confirmation. Results A total of four patients completed the sestamibi scan to date. One out of four patients (Patient1) was positive on the sestamibi scan for distant metastasis. In Patient 1, the sestamibi whole-body posterior image demonstrated abnormal focal uptake in the right posterior calvarium and corresponding to an occipital lytic bone lesion on the SPECT/CT (Figure 1). The patient underwent surgical resection of the skull metastasis, and pathology confirmed metastatic thyroid cancer. Five months post-surgery the suppressed Tg was markedly reduced and stable at ~3.2ng/ml. Table 1 shows the sestamibi scan results, subsequent management and follow-up. With confirmation of the location of the metastatic foci in Patient 1, the two negative ¹⁸F-FDG PET/CT that were previously performed one year apart were reviewed again. The radiology reports did not document interpretation of the low-dose localization CT. In retrospect, the lytic skull metastasis was visible on both of the head CT, but could have been easily missed on the PET due to the normal intensive brain ¹⁸F-FDG activity.

Conclusions In this preliminary analysis, ^99mTc-sestamibi was able to identify the source of elevated Tg levels in one out of four DTC patients with biochemical recurrence and negative conventional imaging studies. ^99mTc-sestamibi may have a role in thyroid cancer localization when physical exam, neck ultrasound, radioiodine scan, chest/abdomen CT, and ¹⁸F-FDG PET/CT could not identify. Additional patients are being recruited. Research Support We are grateful for the generous donations from our patients.

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