In Vivo 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 ([¹³¹I]IBA_bHF, [¹³¹I]IB_NHF, and [¹³¹I]HF) were developed through various strategies. Among the three radiotracers, [¹³¹I]IBA_bHF and [¹³¹I]IB_NHF showed excellent in vitro stability (>98%) in saline and PBS 7.4 for 24 h. Also, good stability of [¹³¹I]IB_NHF 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]IBA_bHF, [¹³¹I]HF, and [¹³¹I]IB_NHF 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]IB_NHF 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]IB_NHF would be a satisfactory radiotracer for SPECT imaging of atherosclerosis.