Dataset Information

Iodine-124 Based Dual Positron Emission Tomography and Fluorescent Labeling Reagents for In Vivo Cell Tracking.

ABSTRACT: Understanding the in vivo behavior of experimental therapeutic cells is fundamental to their successful development and clinical translation. Iodine-124 has the longest half-life (4.2 days) among the clinically used positron emitters. Consequently, this isotope offers the longest possible tracking time for directly labeled cells using positron emission tomography (PET). Herein, we have radiosynthesized and evaluated two iodine-124/fluorescein-based dual PET and fluorescent labeling reagents, namely 124I-FIT-Mal and 124I-FIT-(PhS)2Mal for cell surface thiol bioconjugation. 124I-FIT-(PhS)2Mal labeled cells significantly more effectively than 124I-FIT-Mal. It conjugated to various cell lines in 22%-62% labeling efficiencies with prolonged iodine-124 retention. 124I-FIT-(PhS)2Mal mainly conjugated on the cell membrane, which was confirmed by high-resolution fluorescence imaging. The migration of 124I-FIT-(PhS)2Mal labeled Jurkat cells was visualized in NSG mice with excellent target-to-background contrast using PET/CT over 7 days. These data demonstrate that 124I-FIT-(PhS)2Mal can dynamically track cell migration in vivo using PET/CT over a clinically relevant time frame.

SUBMITTER: Pham TT

PROVIDER: S-EPMC7252900 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

Iodine-124 Based Dual Positron Emission Tomography and Fluorescent Labeling Reagents for <i>In Vivo</i> Cell Tracking.

Pham Truc Thuy TT Lu Zhi Z Davis Christopher C Li Chun C Sun Fangfang F Maher John J Yan Ran R

Bioconjugate chemistry 20200311 4

Understanding the <i>in vivo</i> behavior of experimental therapeutic cells is fundamental to their successful development and clinical translation. Iodine-124 has the longest half-life (4.2 days) among the clinically used positron emitters. Consequently, this isotope offers the longest possible tracking time for directly labeled cells using positron emission tomography (PET). Herein, we have radiosynthesized and evaluated two iodine-124/fluorescein-based dual PET and fluorescent labeling reagen ...[more]

PMID: 32129975

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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.

Dataset Information

Iodine-124 Based Dual Positron Emission Tomography and Fluorescent Labeling Reagents for In Vivo Cell Tracking.

Publications

Iodine-124 Based Dual Positron Emission Tomography and Fluorescent Labeling Reagents for <i>In Vivo</i> Cell Tracking.

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