Near Infrared Imaging of Indocyanine Green ... - ACS Publications

Jul 6, 2015 - European Medicines Agency approved near-infrared probe. ICG has been ... Valspodar (PSC-833) was from Tocris Bioscience. (Bristol, U.K.)...
0 downloads 0 Views 1MB Size
Page 1 of 28

Molecular Pharmaceutics

1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Near infrared imaging of indocyanine green distribution in pregnant mice and effects of concomitant medications

Ameer Bishara1a, Michal Meir1a, Emma Portnoy 1, Miri Shmuel1, Sara Eyal 1*

1

Institute for Drug Research, School of Pharmacy, The Hebrew University of Jerusalem,

Jerusalem, Israel

Running Title: Placental transfer of ICG

*Corresponding author: Sara Eyal, PhD, Institute for Drug Research, Room 613, School of Pharmacy, The Hebrew University of Jerusalem, Ein Kerem, Jerusalem, 91120, Israel. Phone: 972-2-675-8667, Fax: 972-2-675-7246, Email: [email protected] a

Ameer Bishara and Michal Meir contributed equally to this work.

ACS Paragon Plus Environment

Molecular Pharmaceutics

2 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

For Table of Contents Use Only Near infrared imaging of indocyanine green distribution in pregnant mice and effects of concomitant medications Ameer Bishara, Michal Meir, Emma Portnoy, Miri Shmuel, Sara Eyal Graphical abstract Near infra-red fluorescence images of mice fetuses whose mothers were treated with indocyanine green in the absence and the presence of rifampin.

ACS Paragon Plus Environment

Page 2 of 28

Page 3 of 28

Molecular Pharmaceutics

3 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Abstract The transfer of indocyanine green (ICG) across the placenta is considered to be very low based on measurements in fetal blood. The goal of this study was to evaluate in mice ICG's distribution within fetuses themselves and effects of concomitant medications on fetal exposure. Midgestational (day 12.5) and late-gestational (day 17.5) age mice were imaged after administration of ICG (0.167 mg), at the presence and the absence of the organic anion transporting polypeptide (OATP) inhibitor rifampin (10 mg/kg, n=11, or 20 mg/kg, n=1) or the P-glycoprotein inhibitor valspodar (12.5 mg/kg). In vivo ICG emission intensity was followed by ex vivo analysis of blood and tissue emission. Both valspodar and rifampin increased ICG's emission intensity within maternal tissues. In addition, valspodar enhanced the ex vivo signal in mid-pregnancy placentae (2.1-fold; p