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Fast 18F labeling of a near-infrared fluorophore enables positron emission tomography and optical imaging of sentinel lymph nodes.

ABSTRACT: We combine a novel boronate trap for F(-) with a near-infrared fluorophore into a single molecule. Attachment to targeting ligands enables localization by positron emission tomography (PET) and near-infrared fluorescence (NIRF). Our first application of this generic tag is to label Lymphoseek (tilmanocept), an agent designed for receptor-specific sentinel lymph node (SLN) mapping. The new conjugate incorporates (18)F(-) in a single, aqueous step, targets mouse SLN rapidly (1 h) with reduced distal lymph node accumulation, permits PET or scintigraphic imaging of SLN, and enables NIRF-guided excision and histological verification even after (18)F decay. This embodiment is superior to current SLN mapping agents such as nontargeted [(99m)Tc]sulfur colloids and Isosulfan Blue, as well as the phase III targeted ligand [(99m)Tc]SPECT Lymphoseek counterpart, species that are visible by SPECT or visible absorbance separately. Facile incorporation of (18)F into a NIRF probe should promote many synergistic PET and NIRF combinations.

SUBMITTER: Ting R

PROVIDER: S-EPMC2957852 | biostudies-other | 2010 Oct

REPOSITORIES: biostudies-other

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Fast 18F labeling of a near-infrared fluorophore enables positron emission tomography and optical imaging of sentinel lymph nodes.

Ting Richard R Aguilera Todd A TA Crisp Jessica L JL Hall David J DJ Eckelman William C WC Vera David R DR Tsien Roger Y RY

Bioconjugate chemistry 20101001 10

We combine a novel boronate trap for F(-) with a near-infrared fluorophore into a single molecule. Attachment to targeting ligands enables localization by positron emission tomography (PET) and near-infrared fluorescence (NIRF). Our first application of this generic tag is to label Lymphoseek (tilmanocept), an agent designed for receptor-specific sentinel lymph node (SLN) mapping. The new conjugate incorporates (18)F(-) in a single, aqueous step, targets mouse SLN rapidly (1 h) with reduced dist ...[more]

PMID: 20873712

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Project description:ObjectiveEndobronchial ultrasound-guided transbronchial needle aspiration is of diagnostic value in hilar/mediastinal (N1/N2) lymph node staging. We assessed the utility of endobronchial ultrasound-guided transbronchial needle aspiration in lung cancer patients with N1/N2 lymph nodes detected on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography.MethodsFifty lung cancer patients with N1/N2 disease on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography underwent endobronchial ultrasound-guided transbronchial needle aspiration for pathological lymph nodes between November 2012 and April 2015. The diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration, lymph node site and size, number of needle passes and complications were evaluated retrospectively from patients' medical records. Malignancy was defined as a maximum standardized uptake value (SUVmax) >2.5.ResultsThe median longest diameter of the 61 lymph nodes (29 subcarinal, 21 right lower paratracheal, 6 left lower paratracheal, 4 right hilar and 1 upper paratracheal) was 23.4 mm (range: 10.4-45.7); the median number of needle passes was 2 (range: 1-5). There were no severe complications. A definitive diagnosis was made by endobronchial ultrasound-guided transbronchial needle aspiration in 39 patients (31 adenocarcinomas, 3 small-cell carcinomas, 2 squamous-cell carcinomas, 3 large-cell neuroendocrine carcinomas). In the remaining 11 patients, the diagnosis was indefinite: insufficient endobronchial ultrasound-guided transbronchial needle aspiration material was collected in two patients and non-specific lymphadenopathy was confirmed by endobronchial ultrasound-guided transbronchial needle aspiration or thoracotomy in the other nine patients. The mean lymph node SUVmax was 7.09 (range: 2.90-26.9) and was significantly higher in true-positive than in false-positive nodes (P < 0.05, t-test). Non-specific lymphadenopathy was diagnosed by expert visual interpretation of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography images in five of the nine patients.ConclusionEndobronchial ultrasound-guided transbronchial needle aspiration accurately diagnoses N1/N2 disease detected on (18)F-fluorodeoxyglucose positron emission tomography/computed tomography.

Project description:Fluorine-18-fluoro-2-deoxy-D-glucose (FDG) is widely used as positron-emission-tomography (PET) radiotracer for the detection and staging of human cancer. Tumor uptake of FDG varies substantially between different cancer types and between patients with the same tumor type. The molecular basis for this heterogeneity is unknown. Using cancer cell lines and primary human tumors of distinct histologic origins, we here show that increased FDG uptake is universally associated with coordinate upregulation of genes within the glycolysis, pentose-phosphate, and other related metabolic pathways. In primary human breast cancers, this FDG signature shows significant overlap with established breast cancer signatures for the “basal-like” disease subtype and “poor prognosis”. FDG high breast cancer showed significantly more gene copy number alterations genome wide than FDG low cancers. About 50 % of primary breast cancers with high FDG uptake and FDG gene expression signature show DNA copy gain encompassing the c-myc gene locus and express gene sets regulated by the transcription factor MYC. Our data shows that FDG-PET marks a distinct subset of “basal-like” human breast cancer which is characterized by MYC and prognostically unfavorable gene expression signatures, suggesting that FDG-PET imaging may be useful to risk-stratify patients with locally advanced breast cancer. Our general strategy to identify molecular determinants of FDG-retention through a genome-wide approach consisted of FDG uptake measurements in cancer cell lines and primary human tumors, the selection of samples with particularly high versus low FDG-retention, and subsequent pathway-based analysis of RNA expression data collected from these samples. Cell line RNA was extracted from a 10 cm plate seeded simultaneously and at the same density as the wells for FDG-uptake assays. For primary human tumor samples, RNA was extracted from macrodissected frozen tumor tissue. All cell line RNA samples and the astrocytoma RNA aliquots were hybridized to Affymetrix U133 Plus 2.0 arrays. All primary breast cancer RNA samples were hybridized to Affymetrix U133A arrays.

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Fast 18F labeling of a near-infrared fluorophore enables positron emission tomography and optical imaging of sentinel lymph nodes.

Publications

Fast 18F labeling of a near-infrared fluorophore enables positron emission tomography and optical imaging of sentinel lymph nodes.

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