68Ga-DOTATATE PET/CT for the detection of inflammation of large arteries: correlation with18F-FDG, calcium burden and risk factors

Abstract

Background: Ga-[1,4,7,10-tetraazacyclododecane-N,N',N″,N'″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) positron emission tomography (PET) is commonly used for the visualization of somatostatin receptor (SSTR)-positive neuroendocrine tumors. SSTR is also known to be expressed on macrophages, which play a major role in inflammatory processes in the walls of coronary arteries and large vessels. Therefore, imaging SSTR expression has the potential to visualize vulnerable plaques. We assessed 68Ga-DOTATATE accumulation in large vessels in comparison to 18F-2-fluorodeoxyglucose (FDG) uptake, calcified plaques (CPs), and cardiovascular risk factors.

Methods: Sixteen consecutive patients with neuroendocrine tumors or thyroid cancer underwent both 68Ga-DOTATATE and 18F-FDG PET/CT for staging or restaging purposes. Detailed clinical data, including common cardiovascular risk factors, were recorded. For a separate assessment, they were divided into a high-risk and a low-risk group. In each patient, we calculated the maximum target-to-background ratio (TBR) of eight arterial segments. The correlation of the TBRmean of both tracers with risk factors including plaque burden was assessed.

Results: The mean TBR of 68Ga-DOTATATE in all large arteries correlated significantly with the presence of CPs (r = 0.52; p < 0.05), hypertension (r = 0.60; p < 0.05), age (r = 0.56; p < 0.05), and uptake of 18F-FDG (r = 0.64; p < 0.01). There was one significant correlation between 18F-FDG uptake and hypertension (0.58; p < 0.05). Out of the 37 sites with the highest focal 68Ga-DOTATATE uptake, 16 (43.2%) also had focal 18F-FDG uptake. Of 39 sites with the highest 18F-FDG uptake, only 11 (28.2%) had a colocalized 68Ga-DOTATATE accumulation.

Conclusions: In this series of cancer patients, we found a stronger association of increased 68Ga-DOTATATE uptake with known risk factors of cardiovascular disease as compared to 18F-FDG, suggesting a potential role for plaque imaging in large arteries. Strikingly, we found that focal uptake of 68Ga-DOTATATE and 18F-FDG does not colocalize in a significant number of lesions.

Figure 1

Colocalized focal vascular uptake of ¹⁸F-FDG and ⁶⁸Ga-DOTATATE. Transverse views of a 61-year-old male patient with hypertension and a history of cardiovascular disease. Positive uptake is present on both ⁶⁸Ga-DOTATATE (upper row) and ¹⁸F-FDG PET/CT (lower row) at the same location in the abdominal aorta of this patient (red circle). Also, serious calcification was detected at the same position. TBR_DOTATATE was 6.18, while TRB_FDG was 2.42.

Figure 2

Focal vascular uptake of ⁶⁸Ga-DOTATATE without corresponding focal ¹⁸F-FDG uptake. Transverse PET/CT images of a 73-year-old male patient with hypertension, hypercholesterolemia, and smoking. Intense focal uptake of ⁶⁸Ga-DOTATATE can be observed in the aortic arch (upper row), whereas no focally increased ¹⁸F-FDG uptake was seen (lower row). TBR_DOTATATE was 7.60, while TRB_FDG was 1.74.

Figure 3

Focal uptake of FDG but not DOTATATE in the vessel wall. Transverse PET/CT images of a 77-year-old male patient. With hypertension, hypercholesterolemia, history of coronary disease and a family history of cardiovascular disease. Intense ¹⁸F-FDG uptake can be observed in the aortic arch (upper row), whereas no focally increased ⁶⁸Ga-DOTATATE uptake can be seen (lower row). TBR_DOTATATE was 1.64, while TRB_FDG was 2.50.

Figure 4

Colocalization of focal ⁶⁸Ga-DOTATATE and ¹⁸F-FDG uptake. Comparison of 37 foci of increased ⁶⁸Ga-DOTATATE uptake (left) and 39 foci of increased ¹⁸F-FDG uptake (right) with respect to colocalized focal uptake of the other radiotracer and calcification. Imaging findings were characterized as concordant when there was agreement in positive detection with both tracers, and as discordant in cases of discrepancy between the two tracers' uptake.

Figure 5

Comparison between high- and low-risk groups for cardiovascular disease. With regard to the ¹⁸F-FDG and ⁶⁸Ga-DOTATATE uptake of big arterial vessels and calcified plaques. One asterisk indicates that comparison is significant at the 0.05 level (two-tailed).