PET imaging with small-molecule tyrosine kinase inhibitors: TKI-PET

• Published in: Drug discovery today Vol. 17; no. 21-22; pp. 1175 - 1187
• Main Authors: Slobbe, Paul, Poot, Alex J., Windhorst, Albert D., van Dongen, Guus A.M.S.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.11.2012; Elsevier
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Biological and medical sciences; Clinical Trials as Topic; Drug Design; Drug Evaluation, Preclinical; General pharmacology; Humans; Medical sciences; Molecular Targeted Therapy; Neoplasms - drug therapy; Neoplasms - pathology; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Positron-Emission Tomography - methods; Precision Medicine - methods; Protein Kinase Inhibitors - chemical synthesis; Protein Kinase Inhibitors - pharmacology; Protein-Tyrosine Kinases - antagonists & inhibitors; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacology; Ethylene terephthalate polymer; Pharmaceutical technology; Enzyme; Tyrosine kinase inhibitor; Transferases; Ester polymer; Enzyme inhibitor; Medical imagery; Small molecule; Protein-tyrosine kinase; Emission tomography
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2012.06.016

► Radiolabeling of TKIs. ► PET imaging of TKIs in drug development. ► TKI-PET as tool for personalized therapy. The discovery and increased understanding of tumor targets has led to the development and approval of 12 small molecule tyrosine kinase inhibitors (TKIs). Despite tremendous efforts in TKI development, treatment efficacies with these therapeutics are still too low and improvements require a personalized medicine approach. Positron emission tomography (PET) with radiolabeled TKIs (TKI-PET) is a tracking, quantification and imaging method, which provides a unique understanding of the behavior of these drugs in vivo and of the interaction with their target(s). In this article we provide an overview of tracer synthesis and development because each TKI requires a tailor made approach. Moreover, we describe current preclinical work and the first proof-of-principle clinical studies on the application of TKI-PET, illustrating the potential of this approach for improving therapy efficacy and personalized cancer treatment. PET imaging with radiolabeled tyrosine kinase inhibitors (TKI-PET) can be of value to predict therapy response in personalized cancer treatment.