Characterization and biodistribution of under-employed gene therapy vector AAV7
Samantha A. Yost, Emre Firlar, Justin D. Glenn, Hayley B.
Carroll, Steven Foltz, April R. Giles, Jenny M. Egley, Elad Firnberg, Sungyeon
Cho, Trang Nguyen, William M. Henry, Karolina J. Janczura, Joseph Bruder, Ye
Liu, Olivier Danos, Subha Karumuthil-Melethil, Sanjana Pannem, Valerie Yost,
Yelena Engelson, Jason T. Kaelber, Hemi Dimant, Jared B. Smith, Andrew C.
Mercer
Journal of Virology. 2023 Oct 16; 10.1128/jvi.01163-23
Summary
Role of Xerra | Cryofluorescence
tomography (CFT) of whole mice was performed using an Xerra imager (Emit Imaging) 3 weeks after IV administration of AAV7 or AAV9 carrying an EGFP transgene or co-administration of AAV7.CAG.EGFP and AAV9.CAG.tdTomato (2 ×1014 GC/kg). |
CFT Advantage | CFT supports the biodistribution findings in the brain, showing the presence of weak fluorescence in the brain for both AAV7 and AAV9. A surprising finding from CFT was the presence of fluorescence in facial structures, some of it highly concentrated |
Preclinical Applications | Protein Expression, Biodistribution, Drug Development |
Probes Used
In Xerra™ | EGFP, TdTomato |
Imaging Modalities Shown | CFT, Cryo-electron microscopy, Immunofluorescence |
Animal Model | Female C57Bl/6 mice aged 6–8 weeks (Charles River Laboratories) were acclimated for 48 hours prior to AAV administration and divided into five groups (n = 3 per group): non-treated, AAV7.CAG.EGFP, AAV9.CAG.EGFP, AAV9.CAG.TdTomato, and an equimolar mixture of AAV7.CAG.EGFP and AAV9.CAG.TdTomato. |
Preclinical characterization of novel radiolabeled and fluorescent-labeled Fibroblast Activation Protein (FAP)-targeting ligands using gamma counting, SPECT imaging and Cryo-Fluorescence Tomography (CFT)
Hesterman, Novicki, White, Stokes, Cordova, Toddes, Silva, Burke, Domarkas, Wright, Archibald, Yost, Heimann, DiMagno, Hillier, Patel, Orcut, Amor, Tully, Babich, Hoppin
EANM 2023
Summary
Role of Xerra | Visualize the biodistribution of the FAP imaging candidate compounds |
CFT Advantage | CFT imaging provided higher resolution whole-body information, yielding insights such as the local distribution of the ligand on the surface of the bone and heterogeneity of distribution within the tumor |
Preclinical Applications | Tumor Biology, Biodistribution, Drug Development |
Probes Used
In Xerra™ | ZW800-1 |
Imaging Modalities Shown | SPECT/CT, CFT |
Animal Model | A 1ug mass dose of either [67Cu]RTX-1363 or [ZW800-1]RTX-1341 was administered in 100 uL via tail-vain injection to U-87 MG tumor-bearing mice |
STING Agonist Delivery by Tumour-Penetrating PEG-Lipid Nanodiscs Primes Robust Anticancer Immunity
Eric L. Dane, Alexis Belessiotis-Richards, Coralie Backlund , Jianing Wang, Kousuke Hidaka, Lauren E. Milling, Sachin Bhagchandani, Mariane B. Melo, Shengwei Wu, Na Li, Nathan Donahue, Kaiyuan Ni , Leyuan Ma, Masanori Okaniwa , Molly M. Stevens , Alfredo Alexander-Katz, and Darrell J. Irvine
Nature Materials. 21, 710-720 (2022)
Summary
Role of Xerra | High resolution, high sensitivity imaging of new agents LND-CDN carriers that are clinically viable immunostimulatory drugs to increase the response rate of immunotherapy |
CFT Advantage | 3D validation of histology results; full body biodistribution of agents |
Preclinical Applications | Tumor Biology, Biodistribution, Drug Development |
Probes Used
In Xerra™ | cGAMP-sulfo-Cy5 |
Imaging Modalities Shown | None; some histology |
Animal Model | B6 mice bearing MC38 flank tumours inoculated 7d previously were intravenously administered LND or liposome both labelled with 2.0nmol sulfo-Cy5 dye per mouse via retro-orbital injection, or left untreated |
High-Contrast Detection of Somatostatin Receptor Subtype2 for Fluorescence-Guided Surgery
Servando Hernandez Vargas, Solmaz AghaAmiri, Sukhen C. Ghosh, Michael P. Luciano, Luis C. Borbon, Po Hien Ear, James R. Howe, Jennifer M. Bailey-Lundberg, Gregory D. Simonek, Daniel M. Halperin, Hop S. Tran Cao, Naruhiko Ikoma, Martin J. Schnermann, and Ali Azhdarinia
Mol. Pharmaceutics 2022, 19, 4241−4253
Summary
Role of Xerra | Map out the distribution and signal intensity of conjugates while maintaining anatomical context in a mouse tumor model |
CFT Advantage | High resolution, high sensitivity imaging of MMC(FNIRTag)-TOC and its IR800 counterpart in SSTR2+ and SSTR2− tumors |
Preclinical Applications | Imaging Agent Development, Tumor Biology |
Imaging Modalities Shown | Bioluminescence, Confocal Microscopy, NIRF Imaging, PET/CT |
Animal Model | Athymic female J:Nu nude mice with NEC913/NEC1452 xenografts |
CFT Study Details | Acquisition parameters were Ex/Em = 730 and 794 nm, respectively, and auto exposure was +3× |
Microenvironment-triggered multimodal precision diagnostics
Liangliang Hao, Nazanin Rohani, Renee T. Zhao, Emilia M.
Pulver, Howard Mak, Olivia J. Kelada, Henry Ko, Heather E. Fleming, Frank B.
Gertler & Sangeeta N. Bhatia
Nature Materials. 20, 1440–1448 (2021).
Summary
Role of Xerra | To detect the localization of fluorescent signal in a pattern perfectly aligned with the corresponding anatomical tumors throughout the lung (imaged whole animals after systemic administration of fluorescein amidite (FAM)-labelled PRISM) |
CFT Advantage | CFT was able to detect anatomical tumor location of tumors and a protease-responsive imaging sensors for malignancy (PRISM). Analysis software was used to create fly-through animations and 3D models of the whole animal models. |
Preclinical Applications | Oncology, Drug Discovery |
Probes Used
In Xerra™ | FAM fluorophore in PRISM |
Imaging Modalities Shown | CFT, PET/CT, Confocal Microscopy, Immunofluorescence |
Animal Model | Female BALB/c mice |
Emergent Fluorous Molecules and Their Uses in Molecular Imaging
Chao Wang, Stephen R. Adams, and Eric T. Ahrens
Accounts of Chemical Research. 2021 Aug 3;54(15):3060-3070
Summary
| Role of Xerra | Visualize nanoemulsion (NE) biodistribution |
|---|---|
Role of Xerra | Visualize nanoemulsion (NE) biodistribution |
CFT Advantage | 3D imaging of NE, registration of WL and FL signal, high sensitivity compared to other fluorescence imaging modalities |
Preclinical Applications | Gene Therapy, Oncology, Neurology, Immunology, Drug Discovery |
Probes Used
In Xerra™ | Cy5 λEx/Em: 673/707 |
Imaging Modalities Shown | CFT, 19F and 1H MRI, Bimodal PET/MRI, PET, CT, CFT, IVIS |
Animal Model | Acute Inflammation Murine Model |
Brain Pharmacology of Intrathecal Antisense Oligonucleotides Revealed Through Multimodal Imaging
Mazur C, Powers B, Zasadny K, Sullivan JM, Dimant H, Kamme F, Hesterman J, Matson J, Oestergaard M, Seaman M, Holt RW, Qutaish M, Polyak I, Coelho R, Gottumukkala V, Gaut CM, Berridge M, Albargothy NJ, Kelly L, Carare RO, Hoppin J, Kordasiewicz H, Swayze EE, Verma A
Journal of Clinical Investigation Insight. 2019 Oct 17;4(20)
Summary
| Role of Xerra | To define 2D and 3D spatiotemporal pharmacokinetics of ASO penetration in CNS structures and demonstrate their interaction with multiple molecular movement paths. |
|---|---|
Role of Xerra | To define 2D and 3D spatiotemporal pharmacokinetics of ASO penetration in CNS structures and demonstrate their interaction with multiple molecular movement paths. |
CFT Advantage | 2D/3D imaging of ASO brain penetration, registration of WL and FL signal, and collection brain sections on glass slides for fluorescence microscopy and IHC. |
Preclinical Applications | Neurology, Drug Discovery |
Probes Used In Xerra™ | Cy7 λEx/Em: 756/779 |
Imaging Modalities Shown | CFT, SPECT/CT, 18F PET, Microscopy |
Animal Model | Sprague Dawley Rats |
Dynamic Dual-Isotope Molecular Imaging Elucidates Principles for Optimizing Intrathecal Drug Delivery
Wolf DA, Hesterman JY, Sullivan JM, Orcutt KD, Silva MD, Lobo M, Wellman T, Hoppin J, Verma A.
Journal of Clinical Investigation Insight. 2016 Feb 25;1(2)
Summary
| Role of Xerra | To determine the effects of the neuraxial exposure of drug surrogate molecules following an IT lumbar bolus in the rat. |
|---|---|
Role of Xerra | To determine the effects of the neuraxial exposure of drug surrogate molecules following an IT lumbar bolus in the rat. |
CFT Advantage | CFT was used to follow the IT distribution of EBD, a small molecule (MW 961 Da), which binds tightly to albumin and can move from the CSF into the ISF of CNS tissue. Analysis software was used to create fly-through animations and 3D models of the rat spinal column and to estimate CSF volume by application of blue color detectors. |
Preclinical Applications | Neurology, Drug Discovery |
Probes Used In Xerra™ | Cy5 λEx/Em: 673/707 |
Imaging Modalities Shown | MRI, SPECT/CT, Autoradiography, Microscopy |
Animal Model | Sprague Dawley Rats |
