Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Toward preparation of antibody-based imaging probe libraries for dual-modality positron emission tomography and fluorescence imaging.

ABSTRACT: Two novel imaging agents trastuzumab-Cy5.5-CHX-A''1 and cetuximab-Cy7-CHX-A''2, bearing both a chelating moiety (CHX-A'') for sequestering metallic radionuclides ((86)Y or (111)In) and the near infrared dye Cy5.5/Cy7, were prepared by a novel modular synthetic strategy as examples of dual-labeled, antibody-based imaging probe library. Fluorescent microscopy illustrated that 1 and 2 strongly bind to HER2-expressing cancer cells (e.g., NIH3T3-HER2(+), SKOV-3) and to EGFR-expressing cancer cells (e.g., A431), respectively, thereby demonstrating that the functionality of the targeting moiety is conserved. Hence, the described novel synthesis strategy can be applied to engineer other tumor-targeted monoclonal antibody based probes for multimodality imaging.

SUBMITTER: Xu H

PROVIDER: S-EPMC2759299 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Toward preparation of antibody-based imaging probe libraries for dual-modality positron emission tomography and fluorescence imaging.

Xu Heng H Eck Peter K PK Baidoo Kwamena E KE Choyke Peter L PL Brechbiel Martin W MW

Bioorganic & medicinal chemistry 20090527 14

Two novel imaging agents trastuzumab-Cy5.5-CHX-A''1 and cetuximab-Cy7-CHX-A''2, bearing both a chelating moiety (CHX-A'') for sequestering metallic radionuclides ((86)Y or (111)In) and the near infrared dye Cy5.5/Cy7, were prepared by a novel modular synthetic strategy as examples of dual-labeled, antibody-based imaging probe library. Fluorescent microscopy illustrated that 1 and 2 strongly bind to HER2-expressing cancer cells (e.g., NIH3T3-HER2(+), SKOV-3) and to EGFR-expressing cancer cells (e ...[more]

PMID: 19505829

Similar Datasets

Design, synthesis, and characterization of a dual modality positron emission tomography and fluorescence imaging agent for monoclonal antibody tumor-targeted imaging.

Project description:A novel lysine-based trifunctional chelate 3 was designed, synthesized, and characterized and bears both a chelating moiety (CHX-A' ') for sequestering radiometals (86Y or 111In) and the near-infrared dye Cy5.5 for dual modality PET (or SPECT) and fluorescence imaging, respectively. Successful conjugation of 3 to the monoclonal antibody trastuzumab (Herceptin) was achieved by efficient thiol-maleimide chemistry, thereby yielding immunoconjugate 2. Analysis of 2 by flow cytometry and competitive binding assay demonstrates that immunoconjugate 2 binds to SKOV3 tumor cells comparably to native trastuzumab and, thus, may be used as a tumor-targeted monoclonal antibody probe for multimodality imaging.

| S-EPMC2366096 | biostudies-literature

Tau Positron Emission Tomography Imaging.

Project description:Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most common cause of dementia among the elderly population. The good correlation between the density and neocortical spread of neurofibrillary tangles (NFTs) and the severity of cognitive impairment offers an opportunity to use a noninvasive imaging technique such as positron emission tomography (PET) for early diagnosis and staging of the disease. PET imaging of NFTs holds promise not only as a diagnostic tool but also because it may enable the development of disease-modifying therapeutics for AD. In this review, we focus on the structural diversity of tau PET tracers, the challenges related to identifying high-affinity and highly selective NFT ligands, and recent progress in the clinical development of tau PET radioligands.

| S-EPMC5411699 | biostudies-literature

Noninvasive positron emission tomography and fluorescence imaging of CD133+ tumor stem cells.

Project description:A technology that visualizes tumor stem cells with clinically relevant tracers could have a broad impact on cancer diagnosis and treatment. The AC133 epitope of CD133 currently is one of the best-characterized tumor stem cell markers for many intra- and extracranial tumor entities. Here we demonstrate the successful noninvasive detection of AC133(+) tumor stem cells by PET and near-infrared fluorescence molecular tomography in subcutaneous and orthotopic glioma xenografts using antibody-based tracers. Particularly, microPET with (64)Cu-NOTA-AC133 mAb yielded high-quality images with outstanding tumor-to-background contrast, clearly delineating subcutaneous tumor stem cell-derived xenografts from surrounding tissues. Intracerebral tumors as small as 2-3 mm also were clearly discernible, and the microPET images reflected the invasive growth pattern of orthotopic cancer stem cell-derived tumors with low density of AC133(+) cells. These data provide a basis for further preclinical and clinical use of the developed tracers for high-sensitivity and high-resolution monitoring of AC133(+) tumor stem cells.

| S-EPMC3926065 | biostudies-literature

Imaging Inflammation with Positron Emission Tomography.

Project description:The impact of inflammation on the outcome of many medical conditions such as cardiovascular diseases, neurological disorders, infections, cancer, and autoimmune diseases has been widely acknowledged. However, in contrast to neurological, oncologic, and cardiovascular disorders, imaging plays a minor role in research and management of inflammation. Imaging can provide insights into individual and temporospatial biology and grade of inflammation which can be of diagnostic, therapeutic, and prognostic value. There is therefore an urgent need to evaluate and understand current approaches and potential applications for imaging of inflammation. This review discusses radiotracers for positron emission tomography (PET) that have been used to image inflammation in cardiovascular diseases and other inflammatory conditions with a special emphasis on radiotracers that have already been successfully applied in clinical settings.

| S-EPMC7922638 | biostudies-literature

A tumor-targeted polymer theranostics platform for positron emission tomography and fluorescence imaging.

Project description:Here, we describe a novel polymer platform suitable for efficient diagnostics and potential theranostics based on 89Zr-labeled N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymer conjugates. A set of polymers differing in molecular weight with either low dispersity or high dispersity were designed and synthesized and their biodistribution in vivo was successfully and precisely observed over 72 h. Moreover, the feasibility of two imaging techniques, fluorescence imaging (FI) and positron emission tomography (PET), was compared using labeled polymer conjugates. Both methods gave comparable results thus showing the enhanced diagnostic potential of the prepared polymer-dye or polymer-chelator-89Zr constructs. The in vivo and ex vivo PET/FI studies indicated that the dispersity and molecular weight of the linear HPMA polymers have a significant influence on the pharmacokinetics of the polymer conjugates. The higher molecular weight and narrower distribution of molecular weights of the polymer carriers improve their pharmacokinetic profile for highly prolonged blood circulation and enhanced tumor uptake. Moreover, the same polymer carrier with the anticancer drug doxorubicin bound by a pH-sensitive hydrazone bond showed higher cytotoxicity and cellular uptake in vitro. Therefore, HPMA copolymers with low dispersity and a molecular weight near the limit of renal filtration can be used as highly efficient polymer carriers of tumor-targeted therapeutics or for theranostics with minimal side effects.

| S-EPMC5551419 | biostudies-literature

Lewis acid-assisted isotopic 18F-19F exchange in BODIPY dyes: facile generation of positron emission tomography/fluorescence dual modality agents for tumor imaging.

Project description:Positron emission tomography (PET) is a powerful technique for imaging biological pathways in vivo, particularly those that are key targets in disease processes. In contrast, fluorescence imaging has demonstrated to be a superior method for image-guided surgery, such as tumor removal. Although the integration of PET and optical imaging could provide an attractive strategy for patient management, there is a significant shortage of established platforms/methods for PET/optical probe construction. In this study, various reaction conditions were explored to develop a simple and fast method allowing for the introduction of [(18)F]-fluoride into BODIPY dyes. Through a systematic optimization of the reaction conditions, we found that BODIPY dyes, including commercial amine-reactive BODIPY succinimidyl esters, may be converted into their radioactive analogues in the matter of minutes via a (18)F-(19)F isotopic exchange reaction promoted by a Lewis acid such as SnCl4. An integrin-targeting RGD peptide was also conjugated with [(18)F]BODIPY® R6G , derived from the commercially available BODIPY® R6G fluorescent tag, to provide a [(18)F]-RGD conjugate in 82% yield. In vivo evaluation of this imaging probe showed a discernible tumor uptake in the U87MG xenograft model. The dual modality imaging properties of the probe was confirmed by ex vivo fluorescence and microPET imaging experiments. In summary, in the matter of minutes, BODIPY dyes were converted into their "hot" radioactive analogues via a (18)F-(19)F isotopic exchange reaction promoted by a Lewis acid. This approach, which can be applied to commercial BODIPY dyes, provides easy access to positron emission tomography/fluorescence dual modality imaging agents.

| S-EPMC3590587 | biostudies-literature

Positron emission tomography imaging of coronary atherosclerosis.

Project description:Inflammation has a central role in the progression of coronary atherosclerosis. Recent developments in cardiovascular imaging with the advent of hybrid positron emission tomography have provided a window into the molecular pathophysiology underlying coronary plaque inflammation. Using novel radiotracers targeted at specific cellular pathways, the potential exists to observe inflammation, apoptosis, cellular hypoxia, microcalcification and angiogenesis in vivo. Several clinical studies are now underway assessing the ability of this hybrid imaging modality to inform about atherosclerotic disease activity and the prediction of future cardiovascular risk. A better understanding of the molecular mechanisms governing coronary atherosclerosis may be the first step toward offering patients a more stratified, personalized approach to treatment.

| S-EPMC4926532 | biostudies-literature

Positron emission tomography imaging of drug-induced tumor apoptosis with a caspase-triggered nanoaggregation probe.

Project description:Drug Design: An (18)F-labeled caspase-3-sensitive nanoaggregation positron emission tomography tracer was prepared and evaluated for imaging the caspase-3 activity in doxorubicin-treated tumor xenografts. Enhanced retention of the (18)F activity in apoptotic tumors is achieved through intramolecular macrocyclization and in situ aggregation upon caspase-3 activation (see picture).

| S-EPMC4077287 | biostudies-literature

A New Positron Emission Tomography Probe for Orexin Receptors Neuroimaging.

Project description:The orexin receptor (OX) is critically involved in motivation and sleep-wake regulation and holds promising therapeutic potential in various mood disorders. To further investigate the role of orexin receptors (OXRs) in the living human brain and to evaluate the treatment potential of orexin-targeting therapeutics, we herein report a novel PET probe ([11C]CW24) for OXRs in the brain. CW24 has moderate binding affinity for OXRs (IC50 = 0.253 ?M and 1.406 ?M for OX1R and OX2R, respectively) and shows good selectivity to OXRs over 40 other central nervous system (CNS) targets. [11C]CW24 has high brain uptake in rodents and nonhuman primates, suitable metabolic stability, and appropriate distribution and pharmacokinetics for brain positron emission tomography (PET) imaging. [11C]CW24 warrants further evaluation as a PET imaging probe of OXRs in the brain.

| S-EPMC7179119 | biostudies-literature

A Conjugate of Pentamethine Cyanine and <sup>18</sup>F as a Positron Emission Tomography/Near-Infrared Fluorescence Probe for Multimodality Tumor Imaging.

Project description:The novel synthesis of a dual-modality, pentamethine cyanine (Cy5) fluorescent, 18F positron emission tomography (PET) imaging probe is reported. The probe shows a large extinction coefficient and large quantum yield in the biologically transparent, near-infrared window (650-900 nm) for in vivo fluorescent imaging. This fluorophore bears the isotope, 18F, giving a 18F-PET/near-infrared fluorescent (NIRF), bi-modal imaging probe, that combines the long-term stability of NIRF and the unlimited penetration depth of PET imaging. The bi-modal probe is labeled with 18F in a quick, one-step reaction, which is important in working with the rapid decay of 18F. The bi-modal probe bears a free carboxyl group, highlighting a PET/NIRF synthon that can be conjugated onto many advanced biomolecules for biomarker-specific in vivo dual-modal PET/NIR tumor imaging, confocal histology, and utility in multi-fluorophore, fluorescence-guided surgery. Its potential in vivo biocompatibility is explored in a quick proof-of-principal in vivo study. The dye is delivered to A549 xenograft flank-tumors to generate PET and NIRF signals at the tumor site. The tumor distribution is confirmed in ex vivo gamma counting and imaging. Pentamethine cyanine (Cy5) has the ability to preferentially accumulate in tumor xenografts. We substitute the PET/NIRF probe for Cy5, and explore this phenomenon.

| S-EPMC5486037 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data