Differential uptake of 68Ga-DOTATOC and 68Ga-DOTATATE in PET/CT of gastroenteropancreatic neuroendocrine tumors

Abstract

Purpose: Abundant expression of somatostatin receptors (sst) is a characteristic of neuroendocrine tumors (NET). Thus, radiolabeled somatostatin analogs have emerged as important tools for both in vivo diagnosis and therapy of NET. The two compounds most often used in functional imaging with positron emission tomography (PET) are 68Ga-DOTATATE and 68Ga- DOTATOC. Both analogs share a quite similar sst binding profile. However, the in vitro affinity of 68Ga-DOTATATE in binding the sst subtype 2 (sst2) is approximately tenfold higher than that of 68Ga-DOTATOC. This difference may affect their efficiency in detection of NET lesions, as sst2 is the predominant receptor subtype on gastroenteropancreatic NET. We thus compared the diagnostic value of PET/CT with both radiolabeled somatostatin analogs (68Ga-DOTATATE and 68Ga-DOTATOC) in the same patients with gastroenteropancreatic NET. Patients and Methods: Twenty-seven patients with metastatic gastroenteropancreatic NET underwent 68Ga-DOTATOC and 68Ga-DOTATATE PET/CT as part of the workup before prospective peptide receptor radionuclide therapy (PRRT). The performance of both imaging methods was analyzed and compared for detection of individual lesions per patient and for eight defined body regions. A region was regarded as positive if at least one lesion was detected in that region. In addition, radiopeptide uptake in terms of the maximal standardized uptake value (SUVmax) was compared for concordant lesions and renal parenchyma. Results: Fifty-one regions were found positive with both 68Ga-DOTATATE and 68Ga-DOTATOC. Overall, however, significantly fewer lesions were detected with 68Ga-DOTATATE in comparison with 68Ga-DOTATOC (174 versus 179, p < 0.05). Mean 68Ga-DOTATATE SUVmax across all lesions was significantly lower compared with 68Ga-DOTATOC (16.9 ± 6.8 versus 22.1 ± 12.0, p < 0.01). Mean SUVmax for renal parenchyma was not significantly different between 68Ga- DOTATATE and 68Ga-DOTATOC (12.6 ± 2.6 versus 12.6 ± 2.7). Conclusions: 68Ga-DOTATOC and 68Ga-DOTATATE possess similar diagnostic accuracy for detection of gastroenteropancreatic NET lesions (with a potential advantage of 68Ga-DOTATOC) despite their evident difference in affinity for sst2. Quite unexpectedly, maximal uptake of 68Ga-DOTATOC tended to be higher than its 68Ga-DOTATATE counterpart. However, tumor uptake shows high inter- and intraindividual variance with unpredictable preference of one radiopeptide. Thus, our data encourage the application of different sst ligands to enable personalized imaging and therapy of gastroenteropancreatic NET with optimal targeting of tumor receptors. © 2013 Springer-Verlag Berlin Heidelberg.