⁶⁴Cu-DOTATATE PET/CT and Prediction of Overall and Progression-Free Survival in Patients with Neuroendocrine Neoplasms

Abstract

Overexpression of somatostatin receptors in patients with neuroendocrine neoplasms (NEN) is utilized for both diagnosis and treatment. Receptor density may reflect tumor differentiation and thus be associated with prognosis. Non-invasive visualization and quantification of somatostatin receptor density is possible by somatostatin receptor imaging (SRI) using positron emission tomography (PET). Recently, we introduced 64 Cu-DOTATATE for SRI and we hypothesized that uptake of this tracer could be associated with overall (OS) and progression-free survival (PFS). Methods We evaluated patients with NEN that had a 64 Cu-DOTATATE PET/CT SRI performed in two prospective studies. Tracer uptake was determined as the maximal standardized uptake value (SUVmax) for each patient. Kaplan-Meier analysis with log-rank was used to determine the predictive value of 64 Cu-DOTATATE SUVmax for OS and PFS. Specificity, sensitivity and accuracy was calculated for prediction of outcome at 24 months after 64 Cu-DOTATATE PET/CT. Results A total of 128 patients with NEN were included and followed for a median of 73 (1-112) months. During follow-up, 112 experienced disease progression and 69 patients died. The optimal cutoff for 64 Cu-DOTATATE SUVmax was 43.3 for prediction of PFS with a hazard ratio of 0.56 (95% CI: 0.38-0.84) for patients with SUVmax > 43.3. However, no significant cutoff was found for prediction of OS.

Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy

“…To evaluate the benefits of this better detection of lesions with [ 64 Cu]-DOTATATE than with [ 68 Ga]-DOTATOC, the correlation between PET image [ 64 Cu]-DOTATATE uptake (expressed in maximal standardized uptake value - SUV max ) and overall (OS)/progression free survival (PFS) was studied during 24 months after [ 64 Cu]-DOTATATE PET/CT acquisition. The conclusion of this study claimed a good correlation/prognostic between SUV max and PFS but not with OS [ 121 ]. The major drawback of these preliminary human studies consist of the affinities differences for the five SSTRs subtypes between DOTATOC and DOTATATE compounds.…”

“…Compared to 68 Ga, in addition to economic advantages, 64 Cu has a lower positron range which leads to a better PET intrinsic resolution and a higher half-life which allows for a more flexible scanning window. The better patient care management and outcomes remain to be proven and the work is in progress to establish these points [ 121 , 125 ]. In parallel, at present, a radiopharmaceutical industrial company submitted a market authorization from FDA for [ 64 Cu]-DOTATATE and thus confirms the interest of copper-64 in SSTRs imaging.…”

Advances in Molecular Imaging and Radionuclide Therapy of Neuroendocrine Tumors

“…In several studies, SSTR imaging was shown not only to correlate with the gene expression of SSTR in NETs but also with the Ki-67-index, and it was found to be an important predictive factor for survival [ 23 , 24 , 25 , 26 , 27 ]. Furthermore, the molecular imaging of NETs has a major impact on treatment planning [ 28 ].…”

“…Recent data show that SSTR-PET/CT with Copper-64 with a SUVmax cutoff of 43.3 could predict PFS after 24 months of follow-up with a moderate accuracy of 57%. However, a matched comparison with the predictive value of Gallium-68-labelled imaging in the same population was missing in the study [ 26 ].…”

Initial Experience with 64Cu-DOTATATE Digital PET of Patients with Neuroendocrine Neoplasms: Comparison with Analog PET

“…Compared with other SSTR-based PET radiopharmaceuticals, 64 Cu-DOTATATE has the advantage of a flexible acquisition time window ranging from 1 to 3 h after injection with the same lesion detection ability [ 15 ]. Recently, we showed that lesion standardized uptake values (SUV max ) derived from 64 Cu-DOTATATE PET/CT provided prognostic information on progression-free survival for patients with NENs [ 16 ].…”