124 I Positron Emission Tomography Versus 131 I Planar Imaging in the Identification of Residual Thyroid Tissue and/or Metastasis in Patients Who Have Well-Differentiated Thyroid Cancer

Introduction

¹²⁴ I was first used over 50 years ago (1), and several recent studies have evaluated ¹²⁴I relative to diagnostic ¹³¹I for (i) similarities of radiopharmacokinetics (2), (ii) evaluation of lesional and whole-body dosimetry (3 –6), and (iii) improved lesion detection in patients who have well-differentiated thyroid cancer (WDTC) (7,8). The objective of this study was to compare the ability of diagnostic ¹²⁴I positron emission tomography (PET) scanning relative to diagnostic ¹³¹I planar whole-body scanning in the detection of residual tissue and/or metastases in patients who have WDTC.

Methods

Patients were eligible for this study who (i) had histologically proven WDTC, (ii) were suspected of having metastatic WDTC (e.g., elevated thyroglobulin levels, recent fine-needle aspiration positive for cancer, and/or suspicious enlarging mass on physical or imaging study), (iii) were referred for ¹³¹I whole-body dosimetry in anticipation of ¹³¹I therapy, and (iv) were over 18 years of age. The prescribed activities for the imaging studies were 1–2 mCi (37–74 MBq) and 1.7 mCi (63 MBq) for ¹³¹I and ¹²⁴I, respectively. Patients who were prepared by withdrawal of thyroid hormone had their ¹³¹I dosimetry performed first. Those prepared with recombinant human thyrotropin (rhTSH) injections were randomized to receive either ¹³¹I or ¹²⁴I first. Studies were performed within 10 days of each other. Acquisition and processing techniques are summarized in Tables 1 and 2. Images that were used for interpretation were performed at 48 hours after administration of either ¹³¹I or ¹²⁴I with the exception of one patient who received ¹²⁴I and was imaged at 24 hours and then withdrew from the study.

For each image, one blinded reader (D.V.N.) categorized every focus of ¹³¹I and ¹²⁴I radioiodine uptake using the following grading system: 1 = definite physiological uptake/artifact, 2 = most likely physiological uptake/artifact, 3 = indeterminate, 4 = residual thyroid tissue/metastasis in the neck/bed, 5 = most likely distant metastasis, or 6 = definite distant metastasis. Foci that were categories as 4, 5, and 6 were considered positive. When available, foci were correlated with other diagnostic imaging studies. This prospective study was approved by the MedStar Institutional Review Board and the Radioactive Drug Research Committee.

Results

Twenty-five patients were evaluated, and the patient characteristics are noted in Table 3. Seventeen patients were prepared with rhTSH and eight with thyroid hormone withdrawal. The patient specific results are shown in Table 4. Of the 25 patients, 8 patients (32%) had a greater number of positive foci observed on the ¹²⁴I images than on the ¹³¹I images (see Fig. 1), which was statistically significant by Wilcoxon matched-pairs signed-ranks test (p < 0.02). Three of these eight patients have had metastasis confirmed in one or more of the additional positive ¹²⁴I foci. ¹²⁴I images demonstrated the same number and location of foci as on ¹³¹I images in 16 patients of whom 14 had no positive foci and 2 had positive foci on both sets of images (two and five foci, respectively). One patient had one additional positive focus on ¹³¹I images that was not seen on ¹²⁴I images. To date, this has not been confirmed as either a metastasis or a false-positive.

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FIG. 1.

Of the 25 sets of ¹²⁴I PET images and ¹³¹I planar whole-body images evaluated, 8 (32%) ¹²⁴I images demonstrated more foci of radioiodine uptake than observed on the ¹³¹I images. Sixteen patients demonstrated either the same number of foci or no foci on the ¹²⁴I images as demonstrated on the ¹³¹I images. Only one patient had one more focus of radioiodine uptake identified on the ¹³¹I images not detected on the ¹²⁴I images. PET, positron emission tomography.

In regard to the number of individual foci of uptake observed (see Fig. 2), a total of 97 positive foci were identified on either ¹²⁴I or ¹³¹I. ¹²⁴I identified 49 positive foci not identified on ¹³¹I, and ¹³¹I identified one positive focus not identified on ¹²⁴I. Examples of ¹³¹I and ¹²⁴I images are shown in Figures 3 and 4. The difference between the number of foci detect with ¹²⁴I versus ¹³¹I was statistically significant using the binomial regression (p < 0.0001).

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FIG. 2.

Of the 25 sets of ¹²⁴I PET images and ¹³¹I planar whole-body images evaluated, 97 foci categorized as residual tissue and/or metastatic WDTC were detected on either ¹²⁴I and/or ¹³¹I images. Forty-nine foci (51%) were detected only on ¹²⁴I images; only one lesion was detected on the ¹³¹I images that was not detected on the ¹²⁴I images. WDTC, well-differentiated thyroid cancer.

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FIG. 3.

Both images were obtained in the same patient. The image on the left is an anterior planar ¹³¹I whole-body image demonstrating ∼18 foci of ¹³¹I uptake indicative of metastatic WDTC. The image on the right is the anterior¹²⁴I PET image from the maximum intensity projection demonstrating multiple additional foci of ¹²⁴I uptake not detected on the ¹³¹I images suggesting metastatic WDTC.

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FIG. 4.

(A) A single projection of the ¹²⁴I PET maximum intensity projection image in the left anterior oblique position with an abnormal focus of uptake (arrow), and (B) an anterior ¹³¹I image in the same patient, which is completely normal. The posterior image was also normal. No planar left anterior oblique (LAO) image was obtained. In (B), a focus has been circled where the abnormality noted on the ¹²⁴I PET image should have been seen on the ¹³¹I image. (C) A transverse CT image of the pelvis demonstrating an abnormal lytic finding in the patient's left pelvic bone (arrow), which corresponds to the abnormal foci of uptake on the ¹²⁴I PET image noted in (A). (D) The fusion of the transverse CT image of the pelvis with the corresponding transverse ¹²⁴I PET image, which demonstrates the utility of fusing the ¹²⁴I PET image with the CT image. The fused images demonstrate that the ¹²⁴I abnormal uptake corresponds precisely to the abnormality on the CT scan (large arrow). In addition to the identification of this abnormality, the ¹²⁴I images demonstrate a second focus of abnormal ¹²⁴I uptake, which correlates with another abnormality in the sacrum on the CT image suggesting metastatic disease (small arrow). In this patient, the ¹²⁴I PET scan identified at least three and possible four foci of radioiodine uptake that were not identified on the ¹³¹I images. All these additional foci were suggestive of metastatic thyroid cancer. CT, computed tomography.

For the patients prepared with thyroid hormone withdrawal (n = 8), ¹³¹I was performed first per the approved protocol. Of these eight patients, five patients had more foci detected on the ¹²⁴I scan than on ¹³¹I scan, two patients had no focus or the same number of foci detected on either scan, and one patient had one more lesion detected on ¹³¹I scan not detected on the ¹²⁴I scan. Of the 17 patients who were prepared with rhTSH injections and were randomized regarding whether they were administered ¹³¹1 or ¹²⁴I first, 10 had ¹³¹I and 7 patients had ¹²⁴I administered first (see Table 4). Of the 10 patients who were administered ¹³¹I first, 9 had no uptake on either scan and 1 had uptake on the ¹²⁴I scan not seen on the ¹³¹I scan. Of the 7 patients who were administered ¹²⁴I first, 4 had no uptake on either scan, 2 had uptake seen on the ¹²⁴I scan not seen on ¹³¹I scan, and 1 had the same uptake seen on both scans.

Discussion

This study demonstrates the superiority of ¹²⁴I PET images relative to ¹³¹I planar whole-body imaging in the detection of residual thyroid tissue and/or metastasis in patients who have WDTC, and we attribute this superiority to at least three factors. First, ¹²⁴I is a positron emitting radionuclide, which can be imaged using a PET scanner, which in turn results in significantly reduced background noise and improved spatial and contrast resolution. Second, PET images, like computed tomography (CT) images and magnetic resonance imaging, are tomographic images. Not only does this allow the images to be reviewed slice by slice, but this also allows the removal of radioactivity in front of and behind the area of the body being evaluated—one of the mechanism for improved contrast resolution. Although not used in this study, the PET tomographic images can be fused with CT and/or magnetic resonance imaging.

Although Phillips et al. first reported the use of ¹²⁴I for the treatment of thyroid carcinoma in 1960 (1), only a few recent studies have been published comparing ¹²⁴I versus ¹³¹I in the detection of residual thyroid tissue and/or metastases secondary to WDTC in humans (7,8). In 2004, Freudenberg et al. demonstrated additional findings on ¹²⁴I images relative to ¹³¹I images in 2/12 (17%) patients. Sixty foci were identified on the ¹²⁴I images and 58 on the ¹³¹I images (7). In 2008, Phan et al. reported that 8 of 20 (40%) patients had foci of ¹²⁴I uptake without corresponding foci of ¹³¹I uptake identified on ¹³¹I planar whole-body imaging. Evaluation by the number of foci detected was not reported (8).

Although these two reports together with our study collectively demonstrate the superiority of ¹²⁴I PET images relative to ¹³¹I planar images, there is variability in the degree of superiority [e.g., 17% (6), 32% (present report), and 40% (8)]. The reasons for the modest difference may be secondary to a difference in the incidence of residual thyroid tissue and/or metastatic disease in the patient populations of the respective facilities, the relatively low number of patients in all the studies, the time from dosing and/or duration of imaging, and instrumentation, to name only a few of the variables.

Finally, our study as well as the other studies have limitations. First and as already noted, our study has a limited number of patients. However, despite the relatively small number of patients, the superiority of ¹²⁴I PET relative to ¹³¹I planar imaging was statistically significant. Second, all foci categorized as 3, 4, or 5 are not necessarily residual thyroid tissue or metastases. Third, artifact heretofore unknown may not have been recognized. For example, recently Abdul-Fatah et al. reported a shine-through artifact in the trachea with ¹²⁴I (9). Fourth, none of the studies compared ¹²⁴I PET-CT with either ¹²³I or ¹³¹I single photon emission computer tomography (SPECT)–CT. Although two recent studies by Schmidt et al. (10) and Spanu et al. (11) reported that SPECT-CT performed with either ¹²³I or ¹³¹I is superior to radioiodine planar imaging, comparison of ¹²⁴I PET with planar radioiodine imaging is reasonable because to our knowledge most facilities perform radioiodine planar imaging and do not routinely perform whole-body radioiodine SPECT-CT scans. Nevertheless, if radioiodine SPECT-CT imaging of the entire body becomes routinely available and performed, then a future study comparing ¹²⁴I PET-CT to ¹²³I and/or ¹³¹I SPECT-CT is warranted, although we would expect ¹²⁴I PET to be superior to either ¹²³I or ¹³¹I SPECT-CT. As Alavi and Basu have pointed out, the latter suffers from (i) poor spatial and contrast resolution, which reduces its ability to detect smaller foci with low concentrations of radiotracers, and (ii) limited speed relative to PET-CT in screening the entire body, which will increase imaging time significantly (12). The final limitation is that this study did not evaluate cost, altered management, or changed patient outcomes.

In regard to the possibility of stunning reducing the ability of the radioiodine that was administered second to detect the same or more foci, we do not believe this was a problem because of two reasons. First, the prescribed activities of ¹³¹I and ¹²⁴I were 74 MBq (2 mCi) and 63 MBq (1.7 mCi), respectively. We believe stunning at these low amounts of radioactivity is infrequent. Second, in the seven patients who were prepared with thyroid hormone withdrawal, the ¹³¹I was administered first as required by the approved protocol. Despite this, ¹²⁴I scans still detect more foci than ¹³¹I scans in five of these patients. This would argue against stunning, or if stunning was present, then ¹²⁴I PET scans may have been even more sensitive than ¹³¹I scans. For the patients prepared with rhTSH, these patients were randomized regarding the radioiodine isotope that they received first, and as already noted, no statistical difference was demonstrated as a result of the radioiodine that was administered first; however, again, the number of patients is low.

Conclusion

Diagnostic ¹²⁴I PET imaging is superior to diagnostic ¹³¹I planar imaging in identifying a statistically greater number of foci of residual thyroid tissue and/or metastases in statistically more patients with WDTC.

With the present data available, the scientific and commercial communities should partner and pursue a new drug application with the Food and Drug Administration in the United States to expand the availability of ¹²⁴I.