Patients with suspected recurrence from differentiated thyroid carcinoma, based on an increased thyroglobulin (Tg) level and negative neck ultrasound (US), pose a clinical dilemma. Because standard imaging has a low yield identifying potential recurrence, blind 131 I treatment is often applied. However, a tumor-negative 131 I whole-body scintigraphy (WBS) prevails in 38%-50% of patients. We performed a prospective multicenter observational cohort study to test the hypothesis that 124 I PET/CT can identify the patients with a tumor-negative posttherapy 131 I WBS. Methods: Our study was designed to include 100 patients with detectable Tg and a negative neck US, who were planned for blind 131 I therapy. All patients underwent 124 I PET/CT after administration of recombinant human thyroidstimulating hormone. Subsequently, after 4-6 wk of thyroid hormone withdrawal patients were treated with 5.5-7.4 GBq of 131 I, followed by WBS a week later. The primary endpoint was the number of 131 I therapies that could have been omitted using the predicted outcome of the 124 I PET/CT, operationalized as the concordance of tumor detection by 124 I PET/CT, using post-131 I therapy WBS as the reference test. The study would be terminated if 3 patients had a negative 124 I PET/CT and a positive posttherapy 131 I scan. Results: After inclusion of 17 patients, we terminated the study preliminarily because the stopping rule had been met. Median Tg level at 131 I therapy was 28 μg/L (interquartile range, 129). Eight posttherapy WBS were negative (47%), all of which were correctly predicted by negative 124 I PET/CT. Nine posttherapy WBS showed iodine-avid tumor, of which 4 also had positive 124 I PET/CT findings. Sensitivity, specificity, negative predictive value, and positive predictive value of 124 I PET/CT were 44% (confidence interval [CI], 14%-79%), 100% (CI, 63%-100%), 62% (CI, 32%-86%), and 100% (CI, 40%-100%), respectively. Implementation of 124 I PET in this setting would have led to 47% (8/17) less futile 131 I treatments, but 29% of patients (5/17) would have been denied potentially effective therapy. Conclusion: In patients with biochemical evidence of recurrent differentiated thyroid carcinoma and a tumor-negative neck US, the high false-negative rate of 124 I PET/CT after recombinant human thyroidstimulating hormone 124 I PET/CT as implemented in this study precludes its use as a scouting procedure to prevent futile blind 131 I therapy.

BackgroundStudies on imaging of differentiated thyroid cancer (DTC) using 124I often require a multicenter approach, as the prevalence of DTC is low. Calibration of participating scanners is required to obtain comparable quantification. As determination of a well-defined range of recovery coefficients is complicated for various reasons, a simpler approach based on the assumption that the iodine uptake is highly focal with a background that significantly lacks radioactivity might be more efficient. For each scanner, a linear conversion between known and observed activity can be derived, allowing quantification that can be traced to a common source for all scanners within one study-protocol. The aim of this paper is to outline a procedure using this approach in order to set up a multicenter calibration of PET/CT scanners for 124I.MethodsA cylindrical polyethylene phantom contained six 2-ml vials with reference activities of ~2, 10, 20, 100, 400, and 2000 kBq, produced by dilution from a known activity. The phantom was scanned twice on PET/CT scanners of participating centers within 1 week. For each scanner, the best proportional and linear fit between measured and known activities were derived and based on statistical analyses of the results of all scanners; it was determined which fit should be applied. In addition, a Bland-Altman analysis was done on calibrated activities with respect to reference activities to asses the relative precision of the scanners.ResultsNine Philips (vendor A) and nine Siemens (vendor B) PET/CT scanners were calibrated in a time period of 3 days before and after the reference time. No significant differences were detected between the two subsequent scans on any scanner. Six fitted intercepts of vendor A were significantly different from zero, so the linear model was used. Intercepts ranged from −8 to 26 kBq and slopes ranged from 0.80 to 0.98. Bland-Altman analysis of calibrated and reference activities showed that the relative error of calibrated activities was smaller than that of uncalibrated activities.ConclusionsA simplified multicenter calibration procedure for PET/CT scans that show highly focal uptake and negligible background is feasible and results in more precise quantification. Our procedure can be used in multicenter 124I PET scans focusing on (recurrent) DTC.