Key result
[68Ga]Ga-NOTA-folate demonstrated a significantly higher plaque-to-healthy vessel wall ratio (2.44) compared to 18F-FDG (1.93, P=0.005) in atherosclerotic mice.
Why the study?
Folate receptor β is expressed on macrophages and represents a promising target for imaging inflammation, prompting the radiosynthesis and preclinical evaluation of [68Ga]Ga-NOTA-folate.
Absolute Event Rate: 2.44% vs 1.93%
p-value: p=0.005
68Ga-FOL is a promising new FR-β-targeted PET tracer for imaging macrophage-associated inflammation in atherosclerosis, demonstrating higher plaque-to-vessel wall ratio and lower myocardial uptake than 18F-FDG.
68Ga-FOL enables targeted macrophage PET in atherosclerosis models; leaves open clinical translation and validation.
Folate receptor β (FR-β) is one of the markers expressed on macrophages and a promising target for imaging of inflammation. Here, we report the radiosynthesis and preclinical evaluation of [ 68 Ga]Ga-NOTA-folate ( 68 Ga-FOL). First, we determined the affinity of 68 Ga-FOL using human FR-β expressing cells. Then, we studied atherosclerotic mice with 68 Ga-FOL and 18 F-FDG PET/CT. After sacrifice, the tissues excised were measured with a γ-counter for ex vivo biodistribution. Further, the tracer distribution and co-localization with macrophages in aorta cryosections were studied using autoradiography, hematoxylin-eosin staining and immunostaining with anti-Mac-3 antibody. Specificity of 68 Ga-FOL was assessed in a blocking study with excess of folate glucosamine. As a last step, human radiation doses were extrapolated from rat PET data. We were able to produce 68 Ga-FOL at high radioactivity concentration, with high molar activity and radiochemical purity. The cell binding studies showed high (5.1 ± 1.1 nM) affinity of 68 Ga-FOL to FR-β. The myocardial uptake of 68 Ga-FOL (SUV 0.43 ± 0.06) was 20-folds lower compared to 18 F-FDG (SUV 10.6 ± 1.8, P = 0.001). The autoradiography and immunohistochemistry of aorta revealed that 68 Ga-FOL radioactivity co-localized with Mac-3-positive macrophage-rich atherosclerotic plaques. The plaque-to-healthy vessel wall ratio of 68 Ga-FOL (2.44 ± 0.15) was significantly higher than that of 18 F-FDG (1.93 ± 0.22, P = 0.005). Blocking studies verified 68 Ga-FOL specificity to FR. As estimated from rat data the human effective dose was 0.0105 mSv/MBq. The organ with highest absorbed dose was kidney (0.1420 mSv/MBq). In conclusion, 68 Ga-FOL is a promising new FR-β-targeted tracer for imaging macrophage-associated inflammation. TABLE OF CONTENT/ABSTRACT GRAPHIC
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Moisio et al. (2020) studied Atherosclerosis. [68Ga]Ga-NOTA-folate vs. 18F-FDG was evaluated on Plaque-to-healthy vessel wall ratio (p=0.005). [68Ga]Ga-NOTA-folate demonstrated a significantly higher plaque-to-healthy vessel wall ratio (2.44) compared to 18F-FDG (1.93, P=0.005) in atherosclerotic mice.
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