The combination of ¹⁸F-FDG and ¹⁸F-NaF uptake predict the development of abdominal aortic aneurysm in rat model.

Objectives: Abdominal aortic aneurysms (AAAs) expand over time and increase the risk of fatal rupture¹. Atherosclerosis and inflammatory cell infiltration are involved in the evolution of the lesion^2-4. We studied the role of inflammation, using ¹⁸F-FDG PET/CT and lesion necrosis, using ¹⁸F-NaF PET/CT in the evolution of experimental abdominal aortic aneurysm (AAA). Methods: 28 male Sprague- Dawley rats were divided into 4 groups. AAA model (AAA group, n=8) was simulated in the lower abdominal aorta (below renal artery) by placing of 0.5M CaCl₂ soaked gauze for 20 minutes on the vessel while the control group (Vehicle, n=8) were simulated with gauze soaked in saline. To determine the potential effects of medication, Two additional groups of AAA animals received either 20mg/kg of Atorvastatin (Atorvastatin group, n=7) or 12.5mg/kg of Losartan (Losartan group, n=5) every day for 8 weeks. The animals were imaged on a Clavivo micro PET/Rigaku micro CT with both NaF and FDG at 1, 2, 4, 6, and 8 weeks after surgery. After the final image, the aorta was removed en-bloc for-autoradiography and scintillation well counting. The size of the aorta was determined from CT images. Following gamma counting, aortic specimens were fixed overnight with 4% paraformaldehyde. Data are presented as median (interquartile range [IQR]; i.e., 25th to 75th percentile, or Q1, Q3) or as mean ± 1 SD. All parameters were assessed using the Shapiro-Wilk test, Levene’s test, one-way analysis of variance (ANOVA) with Tukey’s HSD post-hoc analysis and p < 0.05 was considered statistically significant. Results: Abdominal cross-section area increased in each group and was significantly higher in all aneurysm groups compared with the vehicle control animals. Compared with the AAA group, the Atorvastatin group showed significantly lower area (Area at 8 weeks, AAA group: 3.02 ± 0.29 mm²; Vehicle:1.44 ± 0.04 mm²; Atorvastatin group 2.45 ± 0.23 mm²; Losartan group 2.78 ± 0.30 mm², p<0.05). Autoradiography showed NaF uptake in the lower abdominal aorta and gamma counting confirmed significantly higher uptake in this area (AAA group lower aorta 1.72 (1.66-3.18) %ID/g; AAA model upper aorta 0.03 (IQR:0.02-0.04) %ID/g; Control lower aorta 0.06 (0.04-0.12) %ID/g; Control upper aorta 0.03 (IQR: 0.02-0.08)%ID/g, p<0.05, n=8 each), suggesting that NaF uptake was primarily in the diseased area. On serial PET CT images, abdominal FDG uptake was significantly higher at 1 and 2 weeks compared with control, while abdominal NaF uptake was significantly higher at all time points. Animals treated with Atorvastatin and Losartan group showed significantly lower FDG and NaF uptake in 1 week, while only Atorvastatin treatment showed lower NaF uptake in 2 weeks (FDG uptake at 1 weeks, AAA group: 0.053 ± 0.012 SUVmax; Vehicle:0.007 ± 0.001 SUVmax; Atorvastatin group :0.034 ± 0.009 SUVmax; Losartan group 0.030 ± 0.009 mm², p<0.05) (NaF uptake at 1 weeks, AAA group: 0.075 ± 0.016 SUVmax; Vehicle:0.006 ± 0.001 SUVmax; Atorvastatin group :0.044 ± 0.020 SUVmax; Losartan group 0.050 ± 0.021 mm², p<0.05). The multiple variable analysis showed the combination of FDG and NaF uptake in 1 week were strongest predicter for the abdominal aorta size at the conclusion of the experiment (r=0.88, p<0.0001). Conclusion: In this model of AAA NaF, uptake was elevated at all time points, and appears to be a more sensitive indicator of evolution of the aneurysm. Research Support: Grants-in-Aid for Scientific Research (KAKENHI) and the Senshin Medical Research Foundation to TN.