Re‐engineered imaging agent using biomimetic approaches

Background:: Epigenetic dysfunction is implicated in many neurologic, psychiatric and oncologic diseases. Consequently, histone deacetylases (HDACs) inhibitors have been developed as therapeutic and imaging agents for these diseases. However, only a few radiotracers have been developed as HDACs imaging agents for the central nervous system (CNS). We report herein the synthesis and evaluation of [18F]INER-1577-3 ([18F]5) as an HDACs imaging agent for CNS. Methods:: [18F]INER-1577-3 ([18F]5) was synthesized by two methods: one-step (A) and two-step (B) methods. Briefly, radiofluorination of the corresponding precursors (11, 12) with K[18F]/K2.2.2 followed by purifications with HPLC gave ([18F]5). The quality of [18F]INER- 1577-3 synthesized by these methods was verified by HPLC and TLC as compared to an authentic sample. The inhibitions of [18F]INER-1577-3 and related HDACs inhibitors on tumor cells growth were carried out with breast cancer cell line 4T1 and MCF-7. The whole-body and brain uptake of [18F]INER-1577-3 in rats and AD mice were determined using a micro-PET scanner and the data was analyzed using PMOD. Results: : The radiochemical yield of [18F]INER-1577-3 synthesized by these two methods was 1.4 % (Method A) and 8.8% (Method B) (EOB), respectively. The synthesis time was 115 min and 100 min, respectively, from EOB. The inhibition studies showed that INER-1577-3 has a significant inhibitory effect in HDAC6 and HDAC8 but not HDAC2. PET studies in rats and AD mice showed a maximum at about 15 min postinjection for the whole brain of a rat (0.47 ± 0.03 %ID/g), SAMP8 mice (5.63 ± 1.09 %ID/g) and SAMR1 mice (7.23 ± 1.21 %ID/g). Conclusion:: This study showed that INER-1577-3 can inhibit tumor cell growth and is one of a few HDACs inhibitors that can penetrate the blood-brain barrier (BBB) and monitor HDAC activities in AD mice. Thus, [18F]INER-1577-3 may be a potent HDACs imaging agent, especially for CNS.

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Gram-scale synthesis of a neodymium chelate as a spectral CT and second near-infrared window imaging agent for visualizing the gastrointestinal tract in vivo

Journal of Materials Chemistry B ◽

10.1039/d0tb02276d ◽

2021 ◽

Author(s):

Pengrui Zhuang ◽

Ke Xiang ◽

Xiangxi Meng ◽

Guohe Wang ◽

Ziyuan Li ◽

...

Keyword(s):

Gastrointestinal Tract ◽

Fluorescence Imaging ◽

Large Scale ◽

Near Infrared ◽

Imaging Agent ◽

Spectral Ct ◽

Green Method ◽

Infrared Window

A facile and green method was developed to fabricate Nd-DTPA on a large scale without byproducts for CT/spectral CT and NIR II fluorescence imaging of the gastrointestinal tract in vivo.

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