Radiosynthesis of ML03 (N-{4 Key words: carbon-11; cancer; biodistribution; PET; EGFrGrowth factors mediate their pleiotropic actions by binding to and activating receptor tyrosine kinases. Epidermal growth factor receptor (EGFr, erb-B1) belongs to a family of proteins involved in the proliferation of normal and malignant cells. 1,2 The binding of activating ligands such as EGF, TGF ␣, AR, BTC or HB-EGF to the EGFr results in activation of the cytosolic kinase domain. Overexpression of EGFr is the hallmark of many human tumors such as breast cancer, glioma, laryngeal cancer, squamous cell carcinoma of the head and neck and prostate cancer. 3 Since the late 1980s continuous effort has been invested in the development of EGFr tyrosine kinase inhibitors as anti-neoplastic drugs. 4,5-11 Radioactively labeled small molecules with high affinity and selectivity for the tyrosine kinase domain of EGFr might offer a specific and sensitive tool to be used in positron emission tomography (PET) for diagnosis of tumors overexpressing EGFr. PET provides 3D and quantitative maps of the distribution of radioactive tracers within the human body and hence permits the measurement of physiological, biochemical and pharmacological function at the molecular level, both in healthy and pathological states. PET is based on the use of short half-life positron-emitting isotopes, such as 11 C (t 1/2 20.39 min.), 18 F (t 1/2 109.8 min.), 15 O (t 1/2 2.037 min.) and 13 N (t 1/2 9.965 min.). After injection of a suitable biomarker, the PET scan provides a mapping of the biomarker distribution and hence of a specific receptor, transporter or enzyme in the human body. Biomarkers with high selectivity for a specific receptor or enzyme might accumulate in those organs and tissues where the targeted protein is overexpressed. In the case of EGFr, its overexpression in human tumors could be non-invasively detected by labeling tyrosine kinase inhibitors with positron-emitting isotopes. The PET application of these potential biomarkers represents a new strategy for the diagnosis of EGFr-expressing tumors. [12][13][14] Moreover, the increasing demand to incorporate diagnostics into clinical studies of EGFr-targeted therapies suggests a potential future use of EGFrTK labeled inhibitors. These labeled inhibitors could help select patients for clinical trials. Cancer patients could undergo a non-invasive diagnostic PET study with labeled EGFrTK inhibitor, and if their tumor is found to overexpress EGFrTK, they could then be selected for a clinical trial that utilizes anti-EGFr therapy.In our previous work, 15 we synthesized, labeled and evaluated 4-(fluoroanilino)quinazoline derivatives as EGFrTK PET biomarkers. These molecules bind reversibly to the ATP binding site of the receptor and inhibit the autophosphorylation of the EGFrTK. Competition with intracellular ATP results in their fast dissociation from the EGFr kinase site, however, making these compounds ineffective as PET reporter probes. We therefore concluded that irreversible EGFr tyrosine kinase ...

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Bromine is a very good electro active species, with fast and reversible kinetics. However, it possesses a high vapor pressure and reactivity which require stabilization via complexing agents, which reduce reactivity and vapor pressure without changing its electrochemical properties. Currently, bromide based batteries like the Zinc/ Bromine cell, use as Bromide complexing agents, either Methyl Ethyl Morpholinium Bromide (MEM) or Methyl Ethyl Pyrrolidinium Bromide (MEP) or their mixture. Both complexing agents have been well known in the field for about 40 years. A possible drawback of their use as complexing agents for bromine is that they are not always compatible with different bromide chemistries. ICL-IP has developed a family of new effective Bromide complexing agents that are compatible with various bromide based chemistries and applications.

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