56 chapter 2 to 100% if only the pattern of 99mTc MIBI uptake lower than or equal to the pertechnetate uptake within the nodule was considered benign. As few benign lesions expressed this uptake pattern, this would decrease the yield of this diagnostic [108]. Piccardo et al. did not preselect hypofunctioning lesions, but included all indeterminate thyroid nodules. As expected given the explanation above, the specificity of [99mTc]Tc-MIBI was poor: 52% [58]. Assessment of a retention index of the tracer based on semi-quantitative measurements of the lesion to non-lesion uptake ratios for early and delayed [99mTc]Tc-MIBI images yielded better accuracy. Optimal thresholds for the retention index were determined using ROC analysis and unfortunately not externally validated [108, 296]. As such, it is unclear whether semi-quantitative [99mTc]Tc-MIBI retention indices are truly more accurate than conventional visual assessment. Moreover, semiquantitative analysis is still operator dependent, as it depends on the manual definition of ranges of interest (ROI)[58]. [99mTc]Tc-MIBI in thyroid nodules with Hürthle cell cytology Oncocytic cells are rich in mitochondria. Therefore, Hürthle cell lesions – malignant as well as benign – frequently show a more intense and persistent [99mTc]Tc-MIBI uptake [296-298]. Boi et al. investigated [99mTc]Tc-MIBI in cold thyroid nodules with varying proportions of Hürthle cells in the cytology samples. A relation between [99mTc]Tc-MIBI uptake and increased tissue density of oncocytes was suggested [298]. Subsequent studies also concluded that [99mTc]Tc-MIBI is not specific enough to differentiate indeterminate lesions with Hürthle cell cytology [108, 293, 296]. Excluding Hürthle cell nodules from [99mTc]Tc-MIBI assessment likely excludes many false-positive tests while improving benign call rate, specificity and overall diagnostic accuracy in indeterminate thyroid nodules. Availability, cost-effectiveness and limitations of [99mTc]Tc-MIBI Imaging of [99mTc]Tc-MIBI requires conventional gamma cameras (with or without single-photon emission computed tomography (SPECT) and CT), which are more widely available than PET, especially in non-Western countries. Furthermore, the tracer itself is more widely available due to relatively simple complexation using [99mTc]Tc-MIBI-kits together with the favourable half-life of 99mTc (~6 hours) obtained from on-site generators. The radiation burden of the recommended wholebody adult dose is 5-6 millisievert, but can be lowered by a factor 2-3 by partial-body imaging [299]. However, the system resolution of state-of-art gamma cameras is a factor 3 lower than of PET/CT cameras. This decreases the measured signal of lesions smaller than 30 mm, increasingly limiting test sensitivity in smaller nodules. Average costs of [99mTc]Tc-MIBI scanning range from €119 to €500 in Europe and from $669 to $1,156 in the USA [177, 300, 301]. From a German perspective, [99mTc]Tc-MIBI-based management was cost-effective over Afirma® GEC-testing and conventional management. However, this study inappropriately extrapolated auspicious performance parameters of [99mTc]Tc-MIBI in unselected thyroid nodules (96% sensitivity and 46% specificity)
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