⁶⁴Cu-DOTATATE for Noninvasive Assessment of Atherosclerosis in Large Arteries and Its Correlation with Risk Factors: Head-to-Head Comparison with ⁶⁸Ga-DOTATOC in 60 Patients

Abstract

The somatostatin receptor subtype 2 is expressed on macrophages, an abundant cell type in the atherosclerotic plaque. Visualization of somatostatin receptor subtype 2, for oncologic purposes, is frequently made using the DOTA-derived somatostatin analogs DOTATOC or DOTATATE for PET. We aimed to compare the uptake of the PET tracers 68 Ga-DOTATOC and 64 Cu-DOTATATE in large arteries, in the assessment of atherosclerosis by noninvasive imaging technique, combining PET and CT. Further, the correlation of uptake and cardiovascular risk factors was investigated. Methods: Sixty consecutive patients with neuroendocrine tumors underwent both 68 Ga-DOTATOC and 64 Cu-DOTATATE PET/CT scans, in random order. For each scan, the maximum and mean standardized uptake values (SUVs) were calculated in 5 arterial segments. In addition, the blood-pool-corrected target-to-background ratio was calculated. Uptake of the tracers was correlated with cardiovascular risk factors collected from medical records. Results: We found detectable uptake of both tracers in all arterial segments studied. Uptake of 64 Cu-DOTATATE was significantly higher than 68 Ga-DOTATOC in the vascular regions both when calculated as maximum and mean uptake. There was a significant association between Framingham risk score and the overall maximum uptake of 64 Cu-DOTATATE using SUV (r 5 0.4; P 5 0.004) as well as target-to-background ratio (r 5 0.3; P 5 0.04), whereas no association was found with 68 Ga-DOTATOC. The association of risk factors and maximum SUV of 64 Cu-DOTATATE was found driven by body mass index, smoking, diabetes, and coronary calcium score (P , 0.001, P 5 0.01, P 5 0.005, and P 5 0.03, respectively). Conclusion: In a series of oncologic patients, vascular uptake of 68 Ga-DOTATOC and 64 Cu-DOTATATE was found, with highest uptake of the latter. Uptake of 64 Cu-DOTATATE, but not of 68 Ga-DOTATOC, was correlated with cardiovascular risk factors, suggesting a potential role for 64 Cu-DOTATATE in the assessment of atherosclerosis.

PET/CT Imaging of Unstable Carotid Plaque with 68Ga-Labeled Somatostatin Receptor Ligand

“…Our results would suggest a lack of significant sst2 expression in macrophages present in recently symptomatic plaques. Our study also adds to the current knowledge in that unlike our study, the retrospective studies mentioned above (26)(27)(28)(29) did not allow study of causation, or molecular mechanism of any observed tracer activity, to the clinical parameters observed. These studies were also performed in patients with chronic plaques only.…”

“…68 Ga has less optimal imaging characteristics compared with 18 F or 64 Cu. 68 Ga-DOTATATE may be less sensitive to weak differences in uptake compared with the equivalent 64 Cu-labeled tracers (29). Higher image noise is reflected by poorer inter-and intraobserver agreement of TBR measurements despite demonstrated excellent agreement in SUV measurements.…”

“…A further study found increased 68 Ga-DOTATATE uptake in coronary plaques compared with normal coronary segments (28). The last compared 68 Ga-DOTATOC and 64 Cu-DOTATATE (29), in correlating vessel uptake against cardiovascular risk factors. 64 Cu-DOTATATE demonstrated a higher uptake than 68 Ga-DOTATOC, with positive correlation with Framingham scores only with 64 Cu-DOTATATE but not with 68 Ga-DOTATOC.…”

“…Recently, 2 preclinical murine studies have demonstrated the potential of somatostatin receptor PET in atherosclerosis imaging (24,25). Retrospective human studies with these tracers have also shown promise (26)(27)(28)(29). In this study, we prospectively explored the use of a clinically established PET tracer, 68 Ga-DOTATATE, a somatostatin receptor ligand, in patients who are believed to have vulnerable carotid plaques, based on recent symptomatic events.…”

Recent Advances in the Development of PET/SPECT Probes for Atherosclerosis Imaging

“…Rinne et al [39] compared several PET probes targeting SSTR-2 in a mouse model and indicated the superior applicabilities of 68 Ga-DOTANOC and 68 Ga-DOTATATE in the detection of atherosclerotic plaques compared with 68 Ga-FDR-NOC. Several clinical studies have also indicated the potential roles of 68 Ga-DOTATATE and 64 Cu-DOTATATE in oncology patients and patients undergoing endarterectomy [6][7][8].…”