Evaluation of an Integrin αvβ3 Radiotracer, [18F]F-FPP-RGD2, for Monitoring Pharmacological Effects of Integrin αv siRNA in the NASH Liver

• Published in: Nuclear medicine and molecular imaging Vol. 57; no. 4; pp. 172 - 179
• Main Authors: Hiroyama, Shuichi, Matsunaga, Keiko, Ito, Miwa, Iimori, Hitoshi, Morita, Ippei, Nakamura, Jun, Shimosegawa, Eku, Abe, Kohji
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01-08-2023; Springer Nature B.V; 대한핵의학회
• Subjects: Alanine; Aspartic acid; Cardiology; Choline; Computed tomography; Emission analysis; Fluorine isotopes; Glycine; Imaging; Liver; Medicine; Medicine & Public Health; Methionine; Monitoring; Nuclear Medicine; Oncology; Original; Original Article; Orthopedics; Positron emission; Proteins; Radioactive tracers; Radiology; Tomography; Transaminases; 방사선과학; Arginine-glycine-aspartic (RGD); Positron emission tomography (PET); Small interfering RNA (siRNA); Integrin; Nonalcoholic steatohepatitis (NASH)
• ISSN: 1869-3474; 1869-3482
• DOI: 10.1007/s13139-023-00791-9

Purpose
Integrin α
v
is a key regulator in the pathophysiology of hepatic fibrosis. In this study, we evaluated the potential utility of an integrin α
v
β
3
positron emission tomography (PET) radiotracer,
18
F-labeled cyclic arginine-glycine-aspartic acid penta-peptide ([
18
F]F-FPP-RGD
2
), for detecting hepatic integrin α
v
and function in nonalcoholic steatohepatitis (NASH) model rats using integrin α
v
siRNA.
Methods
NASH model rats were produced by feeding a choline-deficient, low-methionine, high-fat diet for 8 weeks. PET/computerized tomography imaging and quantification of integrin α
v
protein, serum aspartate aminotransferase, and alanine aminotransferase were performed 1 week after single intravenous injection of integrin α
v
siRNA.
Results
Integrin α
v
siRNA (0.1 and 0.5 mg/kg) dose-dependently decreased hepatic integrin α
v
protein concentrations in control and NASH model rats. The hepatic mean standard uptake value of [
18
F]F-FPP-RGD
2
was decreased dose-dependently by integrin α
v
siRNA. The mean standard uptake value was positively correlated with integrin α
v
protein levels in control and NASH model rats. Serum aspartate aminotransferase and alanine aminotransferase concentrations were also decreased by siRNA injection and correlated with liver integrin α
v
protein expression levels in NASH model rats.
Conclusion
This study suggests that [
18
F]F-FPP-RGD
2
PET imaging is a promising radiotracer for monitoring hepatic integrin α
v
protein levels and hepatic function in NASH pathology.