[PubMed]

Epidermal growth factor (EGF) is a 53-amino acid cytokine (6.2 kDa) secreted by ectodermic cells, monocytes, kidneys and duodenal glands (1). EGF stimulates growth of epidermal and epithelial cells. EGF receptor (EGFR) is a transmembrane protein with an intracellular tyrosine kinase present on most cells. EGFR is overexpressed on many solid tumor cells, such as those of breast, non-small-cell lung, head and neck, and colon cancers (2-4). The high level of EGFR expression on cancer cells is associated with a poor prognosis (5-7). EGF has been labeled with ^99mTc by various laboratories as a potential SPECT imaging agent for EGFR expression on cancer cells (8-11).

The Ras protein is a key regulator in the signaling pathway of the EGFR. Inhibition of farnesylation of Ras in cancer cells by farnesyltransferase inhibitors (FTI) led to inhibition of tumor growth, up regulation of EGFR, and decreased internalization of EGFR (12). ^99mTc-HYNIC-EGF was developed for in vivo prediction of cancer cell response to FTI (8).

[PubMed]

Hydrazinonicotinamide (HYNIC) was conjugated to human EGF to form HYNIC-EGF, which was purified by dialysis with a yield of >94% (8). A mixture of HYNIC-EGF and [^99mTc]pertechnetate (74–370 MBq, 2–10 mCi) in reaction solution was incubated at room temperature for 20 min. ^99mTc-HYNIC-EGF was purified by column chromatography to yield 81-95%, with a radiochemical purity of >95%. The specific activity of ^99mTc-HYNIC-EGF was 1.23 Bq/nmol (33 pCi/nmol) for in vitro binding studies and 3.7–7.4 MBq/nmol (0.1–0.2 mCi/nmol) for the biodistribution studies.

[PubMed]

^99mTc-HYNIC-EGF was found to be stable in Ham’s F12 cell growth medium at 25ºC up to 4 h (8). LoVo human colon adenocarcinoma cells showed a K_d of 3.6 nM with ^99mTc-HYNIC-EGF and 4.0 nM with [¹²⁵I]EGF in saturation binding studies (8, 13). MAb88910 is a monoclonal antibody that inhibits EGF binding to EGFR. MAb88910 showed a K_i value of 1.7 nM and 1.3 nM for blocking ^99mTc-HYNIC-EGF and [¹²⁵I]EGF binding to LoVo cells, respectively (8, 13).

[PubMed]

No publication is currently available.

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Rusckowski M., Qu T., Chang F., Hnatowich D.J. Technetium-99m labeled epidermal growth factor-tumor imaging in mice. J Pept Res. 1997;50(5):393–401. [PubMed: 9401925]

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Yang W., Barth R.F., Leveille R., Adams D.M., Ciesielski M., Fenstermaker R.A., Capala J. Evaluation of systemically administered radiolabeled epidermal growth factor as a brain tumor targeting agent. J Neurooncol. 2001;55(1):19–28. [PubMed: 11804279]

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Capala J., Barth R.F., Bailey M.Q., Fenstermaker R.A., Marek M.J., Rhodes B.A. Radiolabeling of epidermal growth factor with 99mTc and in vivo localization following intracerebral injection into normal and glioma-bearing rats. Bioconjug Chem. 1997;8(3):289–95. [PubMed: 9177833]

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End D.W., Smets G., Todd A.V., Applegate T.L., Fuery C.J., Angibaud P., Venet M., Sanz G., Poignet H., Skrzat S., Devine A., Wouters W., Bowden C. Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res. 2001;61(1):131–7. [PubMed: 11196150]

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Cornelissen B., Thonissen T., Kersemans V., Van De Wiele C., Lahorte C., Dierckx R.A., Slegers G. Influence of farnesyl transferase inhibitor treatment on epidermal growth factor receptor status. Nucl Med Biol. 2004;31(6):679–89. [PubMed: 15246358]