Calcitonin and procalcitonin measurement after cholecystokinin-2/gastrin receptor agonist stimulation in patients with advanced medullary thyroid cancer: results from the GRAN-T-MTC study

Introduction: Medullary thyroid cancer (MTC) is characterized by overexpression of cholecystokinin-2/gastrin receptors (CCK2R). There are limitations of calcitonin as a tumor marker in MTC diagnosis and prognosis. Procalcitonin is gaining a role as a complementary tumor marker. This study aimed to assess the feasibility of procalcitonin measurements on top of the calcitonin measurements after CCK2R agonist stimulation in patients with MTC. Material and methods: The assessment was part of the GRAN-T-MTC translational study conducted through a Phase I multicenter clinical trial in patients with locally advanced and/or disseminated MTC. Patients were administered intravenously the CCK2R agonist CP04 labelled with indium-111 ([111In]In-CP04); the first four patients at a lower mass amount of 10 µg, and afterwards the whole group at a higher mass amount of 50 µg. Blood samples for calcitonin and procalcitonin measurements were obtained shortly before and 2, 5, 10, and 20 minutes after start of [111In]In-CP04 administration. Results: Sixteen patients were included in the study. After injection of the higher mass amount of [111In]In-CP04, the median maximum ratio for stimulated calcitonin was 2.97 (interquartile range [IQR] 2.35) pg/mL and procalcitonin 2.01 (IQR 2.07) pg/mL. The maximum stimulated/baseline calcitonin ratio was 5.2 ± 4.0 and 4.1 ± 3.8 in the low and high mass amount groups, respectively, and the maximum stimulated/baseline procalcitonin ratio was 4.6 ± 5.1 and 2.9 ± 3.1 in the low and high mass amount groups, respectively. There was a significant linear correlation between calcitonin and procalcitonin concentrations (p < 0.001) at each test time point and between the maximum procalcitonin and maximum calcitonin increment ratio (r = 0.94, p < 0.0001). Mild, short-lasting side effects (transient tachycardia, flushing) were observed in one patient during the injection of low and in two patients during the injection of high mass amount of [111In] In-CP04. The side effects were not related to the baseline calcitonin or procalcitonin concentrations. Conclusion: Procalcitonin concentrations after CP04 stimulation were highly correlated with calcitonin concentrations. Unlabeled CP04, if available commercially, may be considered an alternative stimulating agent in MTC patients, even in lower mass amounts. Further studies, including healthy controls, are required to prove this concept and calculate the diagnostic thresholds.