Preclinical

ART Advanced Research Technologies Inc.

ADMET profiling with a novel tumor-targeting NIRF optical probe

Female BALB/c immunodeficient mice (8-9 weeks of age and weighing between 15 and 20 g) were injected with 5 x 10⁶ MDA-MB-231 cells (100 ml volume) subcutaneously at the level of the right scapula. After approximately 3 weeks of tumor growth, the mice were injected via the tail vein with 4 nmol of either free NIR dye (IRDye 800-acid) or NIR-conPK11195 (conjugable PK11195¹ coupled to IRDye 800CW NHS Ester) diluted in 100 ml saline. The biodistribution and accumulation of the free NIR dye and PBR-targeted probe were then monitored at various time points.

Top row: Fluorescence intensity distribution over time for the free NIR dye. From the left, images are: pre-injection, 1, 4, 6, 12, and 24 hours post-injection.

Bottom row: Fluorescence intensity distribution over time for the PBR-targeted probe. From the left, images are: pre-injection, 1, 4, 6, 12, and 24 hours post-injection.

Application Note

In vivo ADME/Tox Profiling Using the ART Optix System with a Novel Targeted Tumor NIR Fluorescent Optical Probe (PDF: 696 Kb)

Log in to download ART application notes.

1. PK11195 was developed at the Vanderbilt University Medical Center and has already been used clinically for imaging neurodegenerative diseases and gliomas.

ART Advanced Research Technologies Inc.

ADMET profiling with a novel tumor-targeting NIRF optical probe

Female BALB/c immunodeficient mice (8-9 weeks of age and weighing between 15 and 20 g) were injected with 5 x 10⁶ MDA-MB-231 cells (100 ml volume) subcutaneously at the level of the right scapula. After approximately 3 weeks of tumor growth, the mice were injected via the tail vein with 4 nmol of either free NIR dye (IRDye 800-acid) or NIR-conPK11195 (conjugable PK11195¹ coupled to IRDye 800CW NHS Ester) diluted in 100  ml saline. The biodistribution and accumulation of the free NIR dye and PBR-targeted probe were then monitored at various time points and ex vivo.

Top row: In vivo fluorescence image 48 hours post-injection and ex vivo fluorescence image of harvested tumor and organs for the free NIR dye.

Bottom row: In vivo fluorescence image 48 hours post-injection and ex vivo fluorescence image of harvested tumor and organs for the PBR-targeted probe.

Application Note

In vivo ADME/Tox Profiling Using the ART Optix System with a Novel Targeted Tumor NIR Fluorescent Optical Probe (PDF: 696 Kb)

Log in to download ART application notes.

1. PK11195 was developed at the Vanderbilt University Medical Center and has already been used clinically for imaging neurodegenerative diseases and gliomas.

Courtesy of Stefania Biffi
Optical Imaging Laboratory, CBM Cluster in Biomedicine
Trieste, Italy

Biodistribution of Cy5.5-conjugated rituximab in mice bearing lymphoid tumor xenograft

BJAB human lymphoblastoid cells were expanded in vitro and then implanted intraperitoneally in the right flank of female severe combined immunodeficiency (SCID) mice. Fifteen to 20 days after implantation, mice that developed a solid mass were treated intraperitoneally or endovenously with 50 mg of rituximab labeled with the Cy5.5 (RI-Cy5.5). Lymphoma-bearing animals were imaged at various time points within the following 7 days.

Images, from the left: Normalized fluorescence images of lymphoma-bearing mouse injected intraperitoneally with RI-Cy5.5 after injection, and 24, 48, 72, 96, and 168 hours post-injection. The probe injection site showed the highest fluorescence signal, which remained confined to a restricted area and was detectable for up to 96 hours.

Paper

In vivo biodistribution and lifetime analysis of Cy5.5-conjugated rituximab in mice bearing lymphoid tumor xenograft using time-domain near-infrared optical imaging
Stefania Biffi, Chiara Garrovo, Paolo Macor, Claudio Tripodo, Sonia Zorzet, Erika Secco, Francesco Tedesco, and Vito Lorusso. Molecular Imaging, Volume 7, Number 6 / November-December 2008: pp. 272-282.

Courtesy of Alain Lepape
Centre National de la Recherche Scientifique (National Center for Scientific Research)
Orleans, France

Distribution of nebulized Cetuximab in mouse lungs

Cetuximab, a chimeric monoclonal antibody that can be used to target EGFR in presence of tumors cells, was used to test nebulization as a means to deliver therapy through the airways for lung cancer treatment. Two mice were subjected to nebulization with Cetuximab labeled with Xenofluor (90 mg/200 ml) and imaged at different times. The in vivo assay performed shows that the distribution of Cetuximab in the lungs was not uniform.

Images (from the left): Intensity image maps at 24, 48, and 72 hours post nebulization.