Performance of Published Glypican 3-Targeting Peptides TJ12P1 and L5 Indicates Lack of Specificity and Potency.

Glypican 3 (GPC3), a plasma membrane heparan sulfate proteoglycan, is overexpressed on human hepatocellular carcinoma and may represent a promising biomarker. Several studies have reported peptides that selectively bind to GPC3 and could serve as scaffolds for imaging or therapeutic agents. We synthesized variants of two previously published peptides, DHLASLWWGTEL (TJ12P1) and RLNVGGTYFLTTRQ (L5), and evaluated their binding performance in paired isogenic cell lines, A431(GPC3) and A431-GPC3 (G1), as well as the liver cancer cell line HepG2.

Integrating Small Animal Irradiators withFunctional Imaging for Advanced Preclinical Radiotherapy Research.

Translational research aims to provide direct support for advancing novel treatment approaches in oncology towards improving patient outcomes. Preclinical studies have a central role in this process and the ability to accurately model biological and physical aspects of the clinical scenario in radiation oncology is critical to translational success. The use of small animal irradiators with disease relevant mouse models and advanced in vivo imaging approaches offers unique possibilities to interrogate the radiotherapy response of tumors and normal tissues with high potential to translate to improvements in clinical outcomes.

High Single Doses of Radiation May Induce Elevated Levels of Hypoxia in Early-Stage Non-Small Cell Lung Cancer Tumors.

Purpose: Tumor hypoxia correlates with treatment failure in patients undergoing conventional radiation therapy. However, no published studies have investigated tumor hypoxia in patients undergoing stereotactic body radiation therapy (SBRT). We aimed to noninvasively quantify the tumor hypoxic volume (HV) in non-small cell lung cancer (NSCLC) tumors to elucidate the potential role of tumor vascular response and reoxygenation at high single doses.

Quantification of Tumor Hypoxic Fractions Using Positron Emission Tomography with [F]Fluoromisonidazole ([F]FMISO) Kinetic Analysis and Invasive Oxygen Measurements.

Purpose: The purpose of this study is to use dynamic [F]fluoromisonidazole ([F]FMISO) positron emission tomography (PET) to compare estimates of tumor hypoxic fractions (HFs) derived by tracer kinetic modeling, tissue-to-blood ratios (TBR), and independent oxygen (pO) measurements.

Procedures: BALB/c mice with EMT6 subcutaneous tumors were selected for PET imaging and invasive pO measurements. Data from 120-min dynamic [F]FMISO scans were fit to two-compartment irreversible three rate constant (K , k , k ) and Patlak models (K ).

Event-by-Event Continuous Respiratory Motion Correction for Dynamic PET Imaging.

Unlabelled: Existing respiratory motion-correction methods are applied only to static PET imaging. We have previously developed an event-by-event respiratory motion-correction method with correlations between internal organ motion and external respiratory signals (INTEX). This method is uniquely appropriate for dynamic imaging because it corrects motion for each time point.

Synthesis of [(18)F]FMISO in a flow-through microfluidic reactor: Development and clinical application.

Introduction: The PET radiotracer [(18)F]FMISO has been used in the clinic to image hypoxia in tumors. The aim of the present study was to optimize the radiochemical parameters for the preparation of [(18)F]FMISO using a microfluidic reaction system. The main parameters evaluated were (1) precursor concentration, (2) reaction temperature, and (3) flow rate through the microfluidic reactor.

Molecular imaging of tumor hypoxia with positron emission tomography.

The problem of tumor hypoxia has been recognized and studied by the oncology community for over 60 years. From radiation and chemotherapy resistance to the increased risk of metastasis, low oxygen concentrations in tumors have caused patients with many types of tumors to respond poorly to conventional cancer therapies. It is clear that patients with high levels of tumor hypoxia have a poorer overall treatment response and that the magnitude of hypoxia is an important prognostic factor.