Background: Somatostatin receptor (SSTR) functional imaging with PET-CT has broadened the diagnostic and staging capabilities for medullary thyroid cancer (MTC). 68Ga-DOTATATE is a radiotracer with a high affinity for type 2 somatostatin receptors (SSTR2) expressed in many but not all MTCs. Correlation between 68Ga-DOTATATE-PET/CT avidity and in-vitro SSTR2 immunohistochemistry has been established in some neuroendocrine tumours (NETs) but not MTC. The utility of 68Ga-DOTATATE-PET/CT and 18F-FDG-PET/CT imaging in predicting MTC prognosis is also unknown.
Methods: In this single centre retrospective study, 37/99 (37%) of MTC patients underwent 68Ga-DOTATATE-PET/CT imaging; of these, 13 (35%) had contemporaneous 18FDG-PET/CT. 68Ga-DOTATATE-PET/CT and 18FDG-PET/CT scans were assessed by two experienced nuclear medicine physicians. SUVmax, SUVmean, metabolic tumour volume (MTV) and total lesion activity (TLA) were assessed for both PET radiotracers. Tumours archived in formalin-fixed paraffin-embedded blocks were constructed into tumour microarrays and immunohistochemistry (IHC) for SSTR2A and Ki67 were scored.
Results: SSTR2A expression was measured by IHC in the primary tumour; 37/99 (37%) had at least some and 62/99 (63%) had no detectable SSTR2A expression. There was no difference in overall survival, calcitonin doubling time or age between SSTR2A +/- tumours. Of the 37 patients with 68Ga-DOTATATE-PET/CT, 32/37 (86%) had avid disease, most commonly in nodal metastases. Ki67 in the primary tumour significantly correlated with 68Ga-DOTATATE MTV (p=0.004) and TLA (p=0.007). SSTR2A IHC did not correlate with 68Ga-DOTATATE avidity. Comparison with 18FDG-PET showed 6/13 patients had 18FDG>68Ga-DOTATATE avidity, 3/13 concordant and 4/13 68Ga-DOTATATE>18FDG avidity. Disease-specific deaths were only seen in the 18FDG >68Ga-DOTATATE avid cohort. Shorter survival was associated with TLA>20 (p=0.04) but not with RET alteration status, calcitonin, or 68Ga-DOTATATE SUVmax or mean.
Conclusion: Assessment of TLA from 68Ga-DOTATATE PET/CT may predict survival. SSTR2A IHC did not correlate with 68Ga-DOTATATE avidity. Metastatic disease may be optimally assessed by concurrent 18FDG and 68Ga-DOTATATE imaging.