Comparative Study of Radioiodinated Folate Receptor Targeting Albumin Probes for Atherosclerosis Plaque Imaging.

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 ([I]IBAHF, [I]IBHF, and [I]HF) were developed through various strategies. Among the three radiotracers, [I]IBAHF and [I]IBHF showed excellent stability (>98%) in saline and PBS 7.4 for 24 h. Also, good stability of [I]IBHF 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 [I]IBAHF, [I]HF, and [I]IBHF 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 [I]IBHF 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, [I]IBHF would be a satisfactory radiotracer for SPECT imaging of atherosclerosis.