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Gd(iii)-Pt(iv) theranostic contrast agents for tandem MR imaging and chemotherapy.

ABSTRACT: Pt(iv) prodrugs have emerged as versatile therapeutics for addressing issues regarding off-target toxicity and the chemoresistance of classic Pt(ii) drugs such as cisplatin and carboplatin. There is significant potential for Pt(iv) complexes to be used as theranostic agents, yet there are currently no reported examples of Gd(iii)-Pt(iv) agents for simultaneous MR imaging and chemotherapy. Here we report the synthesis, characterization, and in vitro efficacy of two Gd(iii)-Pt(iv) agents, GP1 and GP2. Both agents are water soluble and stable under extracellularly relevant conditions but are reduced under intracellular conditions. Both are cytotoxic in multiple cancer cell lines, cell permeable, and significantly enhance the T ₁-weighted MR contrast of multiple cell lines. Thus, GP1 and GP2 are promising agents for tandem MR imaging and chemotherapy and provide a versatile platform through which future Gd(iii)-Pt(iv) agents can be developed.

SUBMITTER: Adams CJ

PROVIDER: S-EPMC8157322 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Gd(iii)-Pt(iv) theranostic contrast agents for tandem MR imaging and chemotherapy.

Adams Casey J CJ Meade Thomas J TJ

Chemical science 20200128 9

Pt(iv) prodrugs have emerged as versatile therapeutics for addressing issues regarding off-target toxicity and the chemoresistance of classic Pt(ii) drugs such as cisplatin and carboplatin. There is significant potential for Pt(iv) complexes to be used as theranostic agents, yet there are currently no reported examples of Gd(iii)-Pt(iv) agents for simultaneous MR imaging and chemotherapy. Here we report the synthesis, characterization, and <i>in vitro</i> efficacy of two Gd(iii)-Pt(iv) agents, < ...[more]

PMID: 34084418

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Project description:BackgroundMRI is very important for guiding the diagnosis and treatment of brachial plexus diseases. The most used type of MRI brachial plexus imaging is the 3D Short Term Inversion Recovery (STIR) sequence with contrast agent. This study aimed to investigate the effect of three contrast agents; gadobenate dimeglumine (Gd-BOPTA), gadopentetate dimeglumine (Gd-DTPA), and Gadoteric Acid Meglumine (Gd-DOTA) on brachial plexus magnetic resonance imaging (MRI).MethodsWe recruited 60 patients with suspected brachial plexus injury randomly into three groups. MRI images were obtained from each patient. Prior to scanning, the first group was injected with GD-BOPTA, the second group with Gd-DTPA, and the third with Gd-DOTA. The amount of contrast agent was 0.1 mmol/kg according to the weight of each patient, the injection rate was 1.5 mL/s, and 20 mL saline was injected at the same rate with a high-pressure injector. Immediately after the injection of contrast agent and saline, a 3D Sampling perfection with application optimized contrasts using different flip angle evolutions (SPACE) STIR sequence was used for scanning. The Signal Intensity (SI) and Standard Deviation (SD) of Maximal intensity projection (MIP) images for regions outside the anatomy (ROI background) with area of 17 mm2 on both sides of the C6 peripheral nerves (ROI nerve), and tissue adjacent to the peripheral nerves (ROI tissue) were obtained. Signal to noise ratio (SNR) and contrast to noise ratio (CNR) were then calculated.ResultsThe SNR was 40.66±25.27, 34.65±14.86, and 44.63±30.79 for Gd-BOPTA, Gd-DTPA, and Gd-DOTA, respectively and the CNR was 20.24±15.17, 16.07±7.50, and 20.84±15.53 for Gd-BOPTA, Gd-DTPA, and Gd-DOTA, respectively. In addition, there was no statistical difference in the SNR or CNR of brachial plexus nerves using the three contrast agents to enhance the 3D SPACE sequence χ2=1.877, P=0.391>0.05 and χ2=1.717, P=0.424, respectively.ConclusionsThere were no significant differences in the efficacy of three contrast agents in imaging the brachial plexus.

Dataset Information

Gd(iii)-Pt(iv) theranostic contrast agents for tandem MR imaging and chemotherapy.

Publications

Gd(iii)-Pt(iv) theranostic contrast agents for tandem MR imaging and chemotherapy.

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