scholarly journals Pharmacokinetics and Biodistribution of Human Serum Albumin-TIMP-2 Fusion Protein Using Near-Infrared Optical Imaging

2011 ◽  
Vol 14 (3) ◽  
pp. 368 ◽  
Author(s):  
Mi-Sook Lee ◽  
Young Han Kim ◽  
Yeon Joo Kim ◽  
Seung-Hae Kwon ◽  
Jeong-kyu Bang ◽  
...  

Purpose TIMP-2 has been studied as an attractive cancer therapeutic candidate, and a TIMP-2 fusion protein (HSA/TIMP-2) displayed effective anticancer activity, despite a lack of information about its pharmacokinetics (PK) and biodistribution. The purpose of this work was to assess the PK and biodistribution of HSA/TIMP-2 as well as to quantify accumulated HSA/TIMP-2 in tumors. Methods Cy5.5 near-infrared (NIR) fluorescence was conjugated to the HSA/TIMP-2 protein (Cy5.5–HSA/TIMP-2) for monitoring spatio-temporal changes in vivo. For PK and biodistribution analysis, 0.2 μg/g body weight of Cy5.5–HSA/TIMP-2 was injected into MAT-LyLu prostate tumor xenografts, which were then imaged using an IVIS-200 optical imaging system. To quantify the accumulated HSA/TIMP-2 in tumors, we introduced a standard curve with depth-corrected fluorescence measurement. Results In the vascular tube formation assay with human umbilical vein endothelial cells (HUVECs), Cy5.5–HSA/TIMP-2 showed an antiangiogenic effect. In prostate cancer xenografts, Cy5.5–HSA/TIMP-2 exhibited a prolongation of blood half-life to 19.6 h and relatively preferential distribution to the tumor. The amount of tumor-accumulated Cy5.5–HSA/TIMP-2 was calculated to be 4.5 ± 0.5 ng/g body weight at 2 days, representing 2.25 ± 0.25% of the initial dose. Conclusions We evaluated the pharmacokinetic profile and biodistribution of HSA/TIMP-2 with favorable results, providing new information for more effective approaches to cancer therapeutics using HSA/TIMP-2. Additionally, real-time in vivo fluorescence imaging analysis using a depth-corrected standard curve may serve as a platform to quantify biodistributed drug in anticancer therapeutic studies. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

2021 ◽  
Author(s):  
Ryohei Saito-Moriya ◽  
Rika Obata ◽  
Shojiro A. Maki

The firefly bioluminescence reaction has been exploited for in vivo optical imaging in life sciences. To develop highly sensitive bioluminescence imaging technology, many researchers have synthesized luciferin analogs and luciferase mutants. This chapter first discusses synthetic luciferin analogs and their structure–activity relationships at the luminescence wavelength of the firefly bioluminescence reaction. We then discuss the development of luciferin analogs that produce near-infrared (NIR) light. Since NIR light is highly permeable for biological tissues, NIR luciferin analogs might sensitively detect signals from deep biological tissues such as the brain and lungs. Finally, we introduce two NIR luciferin analogs (TokeOni and seMpai) and a newly developed bioluminescence imaging system (AkaBLI). TokeOni can detect single-cell signals in mouse tissue and luminescence signals from marmoset brain, whereas seMpai can detect breast cancer micro-metastasis. Both reagents are valid for in vivo bioluminescence imaging with high sensitivity.


2014 ◽  
Vol 10 (1) ◽  
pp. 187-195 ◽  
Author(s):  
Yoichi Shimizu ◽  
Takashi Temma ◽  
Isao Hara ◽  
Akira Makino ◽  
Ryo Yamahara ◽  
...  

Endocrinology ◽  
2012 ◽  
Vol 153 (6) ◽  
pp. 2907-2918 ◽  
Author(s):  
Katrin Büther ◽  
Matthijs G. Compeer ◽  
Jo G. R. De Mey ◽  
Otmar Schober ◽  
Michael Schäfers ◽  
...  

Endothelin (ET) receptor dysregulation has been described in a number of pathophysiological processes, including cardiovascular disorders, renal failure, and cancer. The aim of this study was to evaluate the expression of the ET-A receptor (ETAR) in murine models of thyroid carcinoma using optical imaging methods. A recently developed near-infrared fluorescent tracer was first assessed in isolated artery preparations for its functional performance in comparison with known ETAR antagonists BQ123 and PD156707. Before evaluation of the tracer in vivo, different thyroid carcinoma cell lines were characterized with respect to their ET receptor expression by RT-PCR and autoradiography. In vivo, sc and orthotopic papillary thyroid tumor xenografts were clearly visualized by fluorescence reflectance imaging and fluorescence-mediated tomography up to 48 h after injection of the tracer. Binding specificity of the probe was demonstrated by predosing with PD156707 as a competing inhibitor. In conclusion, optical imaging with a fluorescent ETAR tracer allows the noninvasive imaging of tumor-associated ETAR expression in vivo. In the future, this technique may help surgeons to evaluate lesion dimensions in intraoperative settings (e.g. thyroidectomy).


2015 ◽  
Vol 27 (2) ◽  
pp. 404-413 ◽  
Author(s):  
Kazuhide Sato ◽  
Alexander P. Gorka ◽  
Tadanobu Nagaya ◽  
Megan S. Michie ◽  
Roger R. Nani ◽  
...  

2011 ◽  
Vol 04 (02) ◽  
pp. 199-208
Author(s):  
ZHIQIU LI ◽  
SHUDONG JIANG ◽  
VENKATARAMANAN KRISHNASWAMY ◽  
SCOTT C. DAVIS ◽  
SUBHADRA SRINIVASAN ◽  
...  

A near-infrared (NIR) tomography system with spectrally-encoded sources in two wavelength bands was built to quantify the temporal oxyhemoglobin and deoxyhemoglobin contrast in breast tissue at a 20 Hz bandwidth. The system was integrated into a 3 T magnetic resonance (MR) imaging system through a customized breast coil interface for simultaneous optical and MRI acquisition. In this configuration, the MR images provide breast tissue structural information for NIR spectroscopy of adipose and fibro-glandular tissue in breast. Spectral characterization performance of the NIR system was verified through dynamic phantom experiments. Normal human subjects were imaged with finger pulse oximeter (PO) plethysmogram synchronized to the NIR system to provide a frequency-locked reference. Both the raw data from the NIR system and the recovered absorption coefficients of the breast at two wavelengths showed the same frequency of about 1.3 Hz as the PO output. The frequency lock-in approach provided a practical platform for MR-localized recovery of small pulsatile variations of oxyhemoglobin and deoxyhemoglobin in the breast, which are related to the heartbeat and vascular resistance of the tissue.


2016 ◽  
Vol 4 (33) ◽  
pp. 5560-5566 ◽  
Author(s):  
Lesan Yan ◽  
Huiquan Wang ◽  
Anqi Zhang ◽  
Calvin Zhao ◽  
Yongping Chen ◽  
...  

The IR780@NPs exhibited excellent characteristics for in vivo imaging with a long circulation time and high retention in tumor and sentinel lymph node.


2015 ◽  
Vol 6 (12) ◽  
pp. 4994 ◽  
Author(s):  
Mohammad A. Yaseen ◽  
Vivek J. Srinivasan ◽  
Iwona Gorczynska ◽  
James G. Fujimoto ◽  
David A. Boas ◽  
...  

2014 ◽  
Vol 306 (5) ◽  
pp. R281-R290 ◽  
Author(s):  
Tyler S. Nelson ◽  
Ryan E. Akin ◽  
Michael J. Weiler ◽  
Timothy Kassis ◽  
Jeffrey A. Kornuta ◽  
...  

The ability to quantify collecting vessel function in a minimally invasive fashion is crucial to the study of lymphatic physiology and the role of lymphatic pump function in disease progression. Therefore, we developed a highly sensitive, minimally invasive research platform for quantifying the pumping capacity of collecting lymphatic vessels in the rodent tail and forelimb. To achieve this, we have integrated a near-infrared lymphatic imaging system with a feedback-controlled pressure cuff to modulate lymph flow. After occluding lymphatic flow by inflating a pressure cuff on the limb or tail, we gradually deflate the cuff while imaging flow restoration proximal to the cuff. Using prescribed pressure applications and automated image processing of fluorescence intensity levels in the vessels, we were able to noninvasively quantify the effective pumping pressure (Peff, pressure at which flow is restored after occlusion) and vessel emptying rate (rate of fluorescence clearance during flow occlusion) of lymphatics in the rat. To demonstrate the sensitivity of this system to changes in lymphatic function, a nitric oxide (NO) donor cream, glyceryl trinitrate ointment (GTNO), was applied to the tails. GTNO decreased Peff of the vessels by nearly 50% and the average emptying rate by more than 60%. We also demonstrate the suitability of this approach for acquiring measurements on the rat forelimb. Thus, this novel research platform provides the first minimally invasive measurements of Peff and emptying rate in rodents. This experimental platform holds strong potential for future in vivo studies that seek to evaluate changes in lymphatic health and disease.


2011 ◽  
Vol 52 (9) ◽  
pp. 978-988 ◽  
Author(s):  
Hitoshi Nakayama ◽  
Tomoyuki Kawase ◽  
Kazuhiro Okuda ◽  
Larry F Wolff ◽  
Hiromasa Yoshie

Background In a previous study using a rodent osteosarcoma-grafted rat model, in which cell-dependent mineralization was previously demonstrated to proportionally increase with growth, we performed a quantitative analysis of mineral deposit formation using 99mTc-HMDP and found some weaknesses, such as longer acquisition time and narrower dynamic ranges (i.e. images easily saturated). The recently developed near-infrared (NIR) optical imaging technique is expected to non-invasively evaluate changes in living small animals in a quantitative manner. Purpose To test the feasibility of NIR imaging with a dual-channel system as a better alternative for bone scintigraphy by quantitatively evaluating mineralization along with the growth of osteosarcoma lesions in a mouse-xenograft model. Material and Methods The gross volume and mineralization of osteosarcoma lesions were evaluated in living mice simultaneously with dual-channels by NIR dye-labeled probes, 2-deoxyglucose (DG) and pamidronate (OS), respectively. To verify these quantitative data, retrieved osteosarcoma lesions were then subjected to ex-vivo imaging, weighing under wet conditions, microfocus-computed tomography (μCT) analysis, and histopathological examination. Results Because of less scattering and no anatomical overlapping, as generally shown, specific fluorescence signals targeted to the osteosarcoma lesions could be determined clearly by ex-vivo imaging. These data were well positively correlated with the in-vivo imaging data ( r > 0.8, P < 0.02). Other good to excellent correlations ( r > 0.8, P < 0.02) were observed between DG accumulation and tumor gross volume and between OS accumulation and mineralization volume. Conclusion This in-vivo NIR imaging technique using DG and OS is sensitive to the level to simultaneously detect and quantitatively evaluate the growth and mineralization occuring in this type of osteosarcoma lesions of living mice without either invasion or sacrifice. By possible mutual complementation, this dual imaging system might be useful for accurate diagnosis even in the presence of overlapping tissues.


2020 ◽  
Vol 15 (8) ◽  
pp. 903-915 ◽  
Author(s):  
Maria J. Moreno ◽  
Binbing Ling ◽  
Danica B. Stanimirovic

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