Visualization of Boronic Acid Containing Pharmaceuticals in Live Tumor Cells Using a Fluorescent Boronic Acid Sensor

Boronic acid containing compounds are regarded as a new class of pharmaceuticals, and the distribution in live cells is crucial for the development of novel drugs. However, generic detection methods for boron compounds are not suitable for live-cell imaging, and the fluorescence-labeling technique is challenging to apply for small molecules. Fluorescent boron-sensor DAHMI which is based on a boron chelating ligand was developed for a novel visualization method of boron-based pharmaceuticals in the live cell. In this study, we analyzed the distribution of boronic acid derivatives in live cells using a fluorescent boronic acid sensor

Additional file 1: Figure S1. of Comparison of the pharmacokinetics between L-BPA and L-FBPA using the same administration dose and protocol: a validation study for the theranostic approach using [18F]-L-FBPA positron emission tomography in boron neutron capture therapy

Synthesis of L-FBPA. (PPTX 101 kb

Additional file 2: of Comparison of the pharmacokinetics between L-BPA and L-FBPA using the same administration dose and protocol: a validation study for the theranostic approach using [18F]-L-FBPA positron emission tomography in boron neutron capture therapy

Experimental datasets. (XLSX 62 kb

Time course changes of ¹⁰B concentration in 6 tissues.

<p>¹⁰B concentration in the heart, blood, brain, liver, kidney, lungs, and tumor of PC3 tumor-bearing mice were measured by ICP-AES instrument at 2 and 4 hour after intraperitoneal injection of 250 mg/kg BPA.</p

Ki67 staining on PC3 xenograft specimens.

<p>Xenograft tissues of mice (Group 1: untreated control and Group 4: BPA-mediated BNCT) were stained with Ki67, SMa-actin, and DAPI (A:DAPI B:Ki67 C:SMa-actin D:Mixed). Quantification of Ki67-positive cells was shown.</p

TUNEL staining on PC3 xenograft specimens.

<p>Xenograft tissues of mice (Group 1: untreated control and Group 4: BPA-mediated BNCT) were stained with TUNEL and the number of apoptotic cells was quantified. White arrows indicate TUNEL+ cells.</p

Percentages of animals without gait abnormalities in the four groups.

<p>Gait abnormalities of mice (Group 1: untreated control, Group 2: BPA, Group 3: neutron, Group 4: BPA-mediated BNCT) were observed. The percentages of animals without gait abnormalities differed significantly between Group 4 and Groups 1, 2 and 3 (p<0.05).</p

The mean body weight of mice in four groups.

<p>Mean body weight of mice (Group 1: untreated control, Group 2: BPA, Group 3: neutron, Group 4: BPA-mediated BNCT) from 0 to 9 week were shown. Each point represents the mean body weight ± SEM.</p

The Anti-Proliferative Effect of Boron Neutron Capture Therapy in a Prostate Cancer Xenograft Model - Fig 3

<p><b>(A) Tumor volume of mice in four groups 2 to 9 weeks after PC3 injection.</b> Mean tumor volume of mice (Group 1: untreated control, Group 2: BPA, Group 3: neutron, Group 4: BPA-mediated BNCT) from 2 to 9 week were shown. Each point represents the mean tumor volume ± SEM. *P<0.05 differs from Group 1, 2, and 3 by Student’s t test. <b>(B) Macroscopic findings in four groups at 9 weeks.</b> White arrows indicate sites of tumor.</p