PET Imaging of Receptor Tyrosine Kinases in Cancer

Abstract

Overexpression and/or mutations of the receptor tyrosine kinase (RTK) subfamilies, such as epidermal growth factor receptors (EGFR) and vascular endothelial growth factor receptors (VEGFR), are closely associated with tumor cell growth, differentiation, proliferation, apoptosis, and cellular invasiveness. Monoclonal antibodies (mAb) and tyrosine kinase inhibitors (TKI) specifically inhibiting these RTKs have shown remarkable success in improving patient survival in many cancer types. However, poor response and even drug resistance inevitably occur. In this setting, the ability to detect and visualize RTKs with noninvasive diagnostic tools will greatly refine clinical treatment strategies for cancer patients, facilitate precise response prediction, and improve drug development. Positron emission tomography (PET) agents using targeted radioactively labeled antibodies have been developed to visualize tumor RTKs and are changing clinical decisions for certain cancer types. In the present review, we primarily focus on PET imaging of RTKs using radiolabeled antibodies with an emphasis on the clinical applications of these immunoPET probes. .

WITHDRAWN: Positron Emission Tomographic imaging of tumor cell death using Zirconium-89-labeled APOMAB® following cisplatin chemotherapy in lung and ovarian cancer xenograft models

“…The commercially available DFO-pPhe-NCS bifunctional chelator used in this study may have reduced in vivo stability[45,46], thus contributing to bone accumulation of activity. However, new chelators are being developed and may improve the stability and biodistribution of 89 Zr-labeled mAbs such as [ 89 Zr]Zr-chDAB4, which can generate free [ 89 Zr]Zr IV and result in its uptake by bone.…”

Current outlook on radionuclide delivery systems: from design consideration to translation into clinics

“…The mAbs labeled with a γ- or positron-emitting radionuclide are actively used for quantitative biodistribution imaging using SPECT or PET [28]. The use of mAbs-based PET and SPECT has been implemented in cancer treatment to guide therapy selection, to estimate dosimetry for radioimmunotherapy (RIT), and to track response to therapy [29, 30]. Apart from imaging of oncological targets, immunoPET has been employed for detection and tracking of immune cells [31].…”

Imaging using radiolabelled targeted proteins: radioimmunodetection and beyond

“…For SPECT applications, labelling of intact IgG was performed mainly using 111 In (T 1/2 = 2.8 d) (Behr et al 2001;Perik et al 2006;Desar et al 2010). Since better sensitivity and resolution of PET compared to SPECT might improve imaging using RID, labelling of mAbs with long-lived positron emitters, such as 89 Zr, 64 Cu, 124 I and 86 Y, is gaining an increasing interest (van Dongen et al 2007;Lamberts et al 2015;Wei et al 2018 ). Owing to a dedicated work of Prof. van Dongen and his team from Vrije Universiteit Amsterdam, GMP-produced long lived positron emitters 124 I (T 1/2 = 4.17 d) and 89 Zr (T 1/2 = 3.27 d) are currently commercially available and protocols for their coupling to mAbs are established (Verel et al 2003;Verel et al 2004).…”