Photoacoustic imaging reveals mechanisms of rapid-acting insulin formulations dynamics at the injection site

Khadria, Anjul; Paavola, Chad D.; Maslov, Konstantin; Valenzuela, Francisco A.; Sperry, Andrea E; Cox, Amy L.; Cao, Rui; Shi, Junhui; Brown‐Augsburger, Patricia; Lozano, Emmanuel; Blankenship, Ross L.; Majumdar, Ranajoy; Bradley, Scott A.; Beals, John M.; Oladipupo, Sunday S.; Wang, Lihong V.

doi:10.1016/j.molmet.2022.101522

Cited by 16 publications

(14 citation statements)

References 38 publications

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“…In the first 60 minutes, the area occupied by the antibody increased by 10 – 15% (Figure 2c). This is in stark contrast to a smaller size dye-labeled insulin lispro (∼ 6.8 kDa) in Humalog formulation, whose area was reported to increase by 50 – 60% in the first 60 minutes using the same photoacoustic imaging technique [20]. After 24 hours, the area occupied by the antibody is roughly four times the initial area following injection (Figure 2d).…”

Section: Resultsmentioning

confidence: 86%

“…We designed and employed a triple-wavelength equipped OR-PAM (Figure 1c) to study the near-infrared light absorbing sulfo-cy7.5 dye-labeled IgG4 isotype control antibody in the mouse ear. Our initial efforts to quantify the injection site absorption kinetics of the dye-labeled IgG4 antibody through photoacoustic imaging using the previously reported method were unsuccessful (SI, Figures S1b and S1c) [20]. The results suggested less than 25% of the dye-labeled antibody disappeared from the injection site after the first 3 hours; however, at 6 hours and 24 hours’ time points, the total photoacoustic signal was higher than the total signal just after injection (i.e., at 3 minutes), which could not be the true reflection of the injection site kinetics of the antibody.…”

Section: Resultsmentioning

confidence: 99%

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Photoacoustic imaging reveals transient decrease of oxygenation in murine blood due to monoclonal IgG4 antibody

Khadria

Paavola

Maslov

et al. 2022

Preprint

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Over 100 monoclonal antibodies have been approved by the FDA for clinical use; however, a paucity of knowledge exists regarding the injection site behavior of these formulated therapeutics, i.e., the effect of antibody and formulation on the tissue around the injection site and vice versa. In this report, we injected a near infrared dye labeled IgG4 isotope control antibody in to the subcutaneous space in mouse ear s to analyze the injection site dynamics, including quantifying molecular movement. Surprisingly, we discovered that the antibody reduces the local blood oxygen saturation levels in mice after prolonged anesthesia without affecting the total hemoglobin content and oxygen extraction fraction The local oxygen saturation results open a new pathway to study the functional effects of monoclonal antibodies.

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Section: Resultsmentioning

confidence: 86%

Section: Resultsmentioning

confidence: 99%

Photoacoustic imaging reveals transient decrease of oxygenation in murine blood due to monoclonal IgG4 antibody

Khadria

Paavola

Maslov

et al. 2022

Preprint

Self Cite

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“…In this report, we use optical-resolution photoacoustic microscopy (OR-PAM) (Figure 1a) [29] to simultaneously image blood and lymphatic vessels along with peripheral nerves and sebaceous glands at cellular-level resolution in the mouse ear skin. We used photoacoustic imaging to visualize blood (label-free); however, to image lymphatic vessels, sebaceous glands, and axonal peripheral nerves, we subcutaneously injected the near-infrared light absorbing sulfo-cy7.5 dye-labeled monoclonal human IgG4 isotype control antibody.…”

Section: Mainmentioning

confidence: 99%

Long-duration and non-invasive photoacoustic imaging of multiple anatomical structures in a live mouse using a single contrast agent

Khadria

Paavola

Zhang

et al. 2022

Preprint

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Long-duration in vivo simultaneous imaging of multiple anatomical structures is useful for understanding physiological aspects of diseases, informative for molecular optimization in preclinical models, and has potential applications in surgical settings to improve clinical outcomes. Previous studies involving simultaneous imaging of multiple anatomical structures, e.g., blood and lymphatic vessels as well as peripheral nerves and sebaceous glands, have used genetically engineered mice, which require expensive and time-consuming methods. Here, an IgG4 isotype control antibody is labeled with a near-infrared dye and injected into a mouse ear to enable simultaneous visualization of blood and lymphatic vessels, peripheral nerves, and sebaceous glands for up to 3 hours using photoacoustic microscopy. For multiple anatomical structure imaging, peripheral nerves and sebaceous glands are imaged inside the injected dye-labeled antibody mass while the lymphatic vessels are visualized outside the mass. The efficacy of the contrast agent to label and localize deep medial lymphatic vessels and lymph nodes using photoacoustic computed tomography is demonstrated. The capability of a single injectable contrast agent to image multiple structures for several hours will potentially improve preclinical therapeutic optimization, shorten discovery timelines, and enable clinical treatments.

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“…Bioimaging is the most widely used application of photoacoustic effect and it has gained success in both preclinical and clinical imaging right from imaging anatomical structures, studying drugs, imaging tumors, imaging cellular structures, imaging neuronal function, and histology. [38][39][40][41][42][43] One of the significant advantages of photoacoustic imaging over fluorescence imaging is that it has a higher resolution to depth ratio thus allowing imaging of deeper biological structures at a greater resolution. 36 Given that different biomolecules have unique chemical compositions and light absorption fingerprints, photoacoustic imaging has been employed to image a wide range of biological structures from DNA to lipids to proteins.…”

Section: Photoacoustic Imagingmentioning

confidence: 99%

Nanoparticles as Contrast Agents for Preclinical and Clinical Bioimaging

Ban¹

2022

Preprint

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Visualization of deep biological structures in human and animal bodies is not possible through the naked eye due to the scattering of visible light by tissues in tolerable intensities. Different types of imaging modalities based on electromagnetic and pressure waves have been developed that help us image deep biological tissues with varying resolution and contrast. Some of the most widely used modalities are X-ray imaging, ultrasound imaging, MRI imaging, fluorescence imaging, and photoacoustic imaging. Although these techniques have significantly helped the advancement of our understanding of deep biological tissues and functions, they often require the use of exogenous contrast agents to improve their image quality for better investigation. Nanoparticle-based contrast agents have captivated scientists because of multiple advantages associated with them such as their excellent photophysical and chemical properties, ability to be precisely delivered at the target, and superlative tunability. This article is aimed to give a brief outlook on the recent state of art advances in the usage of nanoparticles for preclinical and clinical bioimaging through fluorescence, photoacoustic, and MRI imaging modalities.

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Photoacoustic imaging reveals mechanisms of rapid-acting insulin formulations dynamics at the injection site

Cited by 16 publications

References 38 publications

Photoacoustic imaging reveals transient decrease of oxygenation in murine blood due to monoclonal IgG4 antibody

Photoacoustic imaging reveals transient decrease of oxygenation in murine blood due to monoclonal IgG4 antibody

Long-duration and non-invasive photoacoustic imaging of multiple anatomical structures in a live mouse using a single contrast agent

Nanoparticles as Contrast Agents for Preclinical and Clinical Bioimaging

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