The
objective of this study is to compare a series of albumin-based
folate radiotracers for the potential imaging of folate receptor (FR)
positive macrophages in advanced atherosclerotic plaques. Diversified
radioiodinated FR-targeting albumin-binding probes ([131I]IBAbHF, [131I]IBNHF, and [131I]HF) were developed through various strategies. Among the
three radiotracers, [131I]IBAbHF and [131I]IBNHF showed excellent in vitro stability
(>98%) in saline and PBS 7.4 for 24 h. Also, good stability of
[131I]IBNHF in mouse serum albumin was monitored
using an HSA ELISA kit. The experiments in Raw264.7 macrophages activated
by ox-LDL confirmed the specificity of tracers for FR-β. Biodistribution
studies of radiotracers were performed to verify the prolonged blood
half-life. Prolonged blood half-lives of [131I]IBAbHF, [131I]HF, and [131I]IBNHF were 17.26 ± 4.29, 6.33 ± 2.64, and 5.50 ± 1.26
h, respectively. SPECT-CT imaging of ApoE–/– mice at different stages was performed to evaluate the progression
and monitor the prognosis of AS. Evident [131I]IBNHF uptake in atherosclerotic lesions could be observed along with
a low background signal. In summary, we demonstrated a proof-of-concept
of albumin-based radioligands for FR-targeting atherosclerosis imaging
and found that different incorporation of radioiodinated groups resulted
in different pharmacokinetic properties. Among these candidate compounds,
[131I]IBNHF would be a satisfactory radiotracer
for SPECT imaging of atherosclerosis.