Micro-SPECT Imaging of Acute Ischemic Stroke with Radioiodinated Riboflavin in Rat MCAO Models via Riboflavin Transporter Targeting

Abstract

Riboflavin transporter-3 (RFVT3) is a recently discovered and novel biomarker for the theranostics of nervous system diseases. RFVT3 is significantly overexpressed in cerebral injury after ischemic stroke. Herein, we first reported an RFVT3targeted tracer 131 I-riboflavin ( 131 I-RFLA) for SPECT imaging of ischemic stroke in vivo. 131 I-RFLA was radiosynthesized by the iodogen-coating method. 131 I-RFLA possessed a radiochemical yield of 69.2 ± 3.7% and greater than 95% radiochemical purity. The representative SPECT/CT images using 131 I-RFLA demonstrated the conspicuously increased tracer uptake in the cerebral injury by comparison with the contralateral normal brain at 1 h and 3 and 7 d after stroke. Ex vivo autoradiography demonstrated that the ratio of infarcted to normal brain uptake was 3.63 and it was decreased to 1.98 after blocking, which reconfirmed the results of SPECT images. Importantly, a significant correlation was identified between RFVT3 expression and brain injury by H&E and immunohistochemistry staining. Therefore, RFVT3 is a new and potential biomarker for the early diagnosis of ischemic stroke. In addition, 131 I-RFLA is a promising SPECT tracer for imaging RFVT3-related ischemic cerebral injury in vivo.

Development of radiotracers for riboflavin transporter 3 imaging in diseases—A brief overview

“…The SPECT/CT images using 131 I-RFLA for imaging ischemic stroke in rat MCAO models demonstrated a higher radioactivity uptake in injured cerebral tissue than that in normal cerebral tissue, which was identified by RFVT3 immunohistochemistry, autoradiography and H&E staining ex vivo. 11 We concluded that RFVT3 is a potential biomarker for addressing stroke-related mitochondrial metabolic reprogramming (Figure 3).…”

“…Our studies found that RFVT3 was overexpressed in the infarcted brain tissue after ischemic stroke compared with normal brain tissue in rat MCAO models. 11 We first designed and radio-synthesized an RFVT3-targeted tracer ( 131 I-riboflavin, 131 I-RFLA) by the iodogen-coating method. 131 I-RFLA possessed high radiochemical yield, radiochemical purity, and favorable pharmacokinetic properties.…”

“…14 RFVT3 has been identified as a potential biomarker for fluorescence imaging and nuclear medicine imaging. 11 To the best of our knowledge, we first report a series of RFVT3-targeting single-photon emission computed tomography (SPECT) and positron emission tomography (PET) probes for imaging multiple diseases, such as nervous system diseases and cancers. 11,15 2 | MAIN TEXT…”

“…11 To the best of our knowledge, we first report a series of RFVT3-targeting single-photon emission computed tomography (SPECT) and positron emission tomography (PET) probes for imaging multiple diseases, such as nervous system diseases and cancers. 11,15 2 | MAIN TEXT…”

A Fluorescent Probe for Investigating the Role of Biothiols in Signaling Pathways Associated with Cerebral Ischemia‐Reperfusion Injury

“…Ischemic stroke accounts for about 80 % of the total number of stroke cases. [1][2][3] At present, reperfusion is an important measure for reversing brain injury after ischemic stroke, [4][5][6] but the treatment may cause secondary cell and tissue damage, called cerebral ischemia-reperfusion injury (CIRI). [7] The pathogenesis is complicated and involves the disorders of energy metabolism, oxidative stress, inflammatory reaction, and excitatory amino acid toxicity.…”