In this study, the performance of FCH PET/CT as a first-line imaging method was investigated. Most studies that have been published on the use of FCH PET/CT in hyperparathyroidism used this scan as a second-line imaging method when conventional imaging methods, such as 99mTc-sestamibi scintigraphy and ultrasonography, were inconclusive, or when previous surgery had failed [12,13,14,15,16,17,18,19]. Fewer studies were published on the performance of FCH PET/CT as a first-line imaging modality, with reported sensitivities ranging between 89% and 100% [20,21,22,23]. The results from the present study, with a detection rate of 96% and 90%, on a per patient-based and a per lesion-based respectively, are in line with these earlier studies.
In this study, the detection rate was calculated as the number of true positives divided by the total of true positives and false negatives. The term detection rate was used instead of sensitivity, because of the highly selected patient population which only contained patients with biochemically proven primary hyperparathyroidism. Additionally, the purpose of imaging is not to confirm or exclude the disease, but to detect and localize the diseased parathyroid glands. Frequently, true negative numbers are not available, because acquiring histopathological proof of intraoperatively normal-looking glands is not recommended and in minimally invasive parathyroidectomy, the other parathyroid glands are not inspected [10]. In this study, both the per patient-based as well as the per lesion-based detection rate were calculated. The use of the lesion-based detection rate is most appropriate, because this number represents the correct localization of the gland, which is essential in preoperative planning. The main strength of this study is the large cohort size, including a substantial group of patients that underwent parathyroidectomy. However, 18% of the patients were treated with medication and 31% received further follow-up without active treatment, and for this part of the cohort, no detection rate could be calculated because of the lack of a reference standard. This subjects the analysis of the operated patient group to selection bias and possibly leads to an overestimation of the detection rates, which are, nevertheless, in accordance with the literature. Prospective trials could reduce this selection bias.
Besides the excellent detection rates of FCH PET/CT, there are several other benefits of this modality above conventional scintigraphy. FCH PET/CT has shorter acquisition times and lower radiation dose, and there is no need to stop calcimimetic drugs. PET/CT scanners have become more commonly available, and the tracer is suitable to be shipped due to the relatively long half-life of 110 min. In general, PET/CT is more expensive than conventional scintigraphy; however, costs can be reduced if an on-site cyclotron is available or when a hospital can act as a referral center with frequent use of the technique. Also, the cost of radiopharmaceuticals could be reduced with more sensitive scanners and more sophisticated software. Cost-effectiveness was not evaluated in this study and has not been investigated in earlier studies but will be relevant for the decision whether to use FCH PET/CT as the first-line imaging method instead of conventional scintigraphy.
It is expected that detection rates will improve with new generation PET/CT scanners. Present digital systems have effective sensitivities up to 98.4 counts per second (cps) per kBq, compared to 9 cps/kBq for the analog Siemens TruePoint PET/CT, used in this study. This is especially relevant for the detection of small lesions such as parathyroid glands. Besides FCH PET/CT, another promising imaging technique is contrast-enhanced CT acquired at multiple time points (4D-CT). Although the performance of CT is good, the main disadvantage is the higher radiation dose [24]. A pilot study demonstrated that FCH PET/CT is comparable in performance to 4D-CT [25], a recent study showed that the combination of FCH PET with 4D-CT was of added value [18], and a third study concluded that 4D-CT appears as a confirmatory imaging modality [19]. Furthermore, an interesting development is the use of FCH PET/MRI, with the reduction of radiation dose and increased soft-tissue resolution [16, 26, 27].
In our institution, choline PET/CT is performed as a first-line imaging method in the routine clinical work-up of hyperparathyroid patients. No 99mTc-sestamibi scintigraphy, CT, or MRI was performed before choline PET/CT in these patients. Also, ultrasound is no prerequisite in our institution. Only patients with primary hyperparathyroidism were included in this study; therefore, no conclusions can be drawn on the use of choline PET/CT as a first-line imaging method in secondary of tertiary hyperparathyroidism. The group of patients in this study was heterogeneous, representing the population in our institution. Both symptomatic and asymptomatic patients were represented and patients with typical elevated serum calcium and PTH levels but also with normocalcemic hyperparathyroidism were included.
In the group of patients who underwent surgery, high detection rates were found, and it can be concluded that in this setting, the choline PET/CT is a useful method to guide the surgeon. A noteworthy part of the studied group, however, did not undergo surgery. In this group (treated with medication or without active treatment), the exact value of the choline PET/CT cannot be assessed, since the influence of the scan on further treatment of the patient and clinical outcome is unclear. One possible explanation for the relatively high rate of non-operated patients is that FCH PET/CT is performed rather early in the diagnostic process in our institution. Regularly, the patients are referred for choline PET/CT by the endocrinologist and are referred for surgical intervention at a later time point. However, the general consensus is that imaging of parathyroid glands is performed for preoperative localization in patients for which operation is already indicated [10]. The value of choline PET/CT or other parathyroid imaging techniques to prove or rule out parathyroid disease is unknown.