{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T09:35:43Z","timestamp":1775986543486,"version":"3.50.1"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,24]],"date-time":"2006-01-24T00:00:00Z","timestamp":1138060800000},"content-version":"vor","delay-in-days":785,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2003,12]]},"abstract":"<jats:p><jats:bold>A<jats:sc>bstract<\/jats:sc>: <\/jats:bold> In 2003, approximately 39,800 women in the US will die from breast cancer. Mammography and physical examination miss up to 40% of early breast cancers. Moreover, if an abnormality is found, an invasive diagnostic procedure must still be performed to determine if the breast contains atypia or cancer, even though approximately 85% of abnormalities are benign. Scintigraphic imaging of gene expression <jats:italic>in vivo<\/jats:italic> by noninvasive means could direct physicians to appropriate targets for intervention at the onset of disease and thereby significantly impact patient management. Until now, no method has been available to image specific overexpressed oncogene mRNAs <jats:italic>in vivo<\/jats:italic> by scintigraphic imaging. We hypothesize that gamma\u2010emitting Tc\u201099m\u2010PNA\u2010peptides can be taken up by human ER+ and ER\u2212 breast cancer xenografts, hybridize to complementary mRNA targets in those cells, and concentrate sufficiently in tumor tissue to allow noninvasive imaging of oncogene overexpression. To prepare the probes, peptide analogs of insulin\u2010like growth factor 1 (IGF1) were extended from a solid support by Fmoc coupling. Peptide nucleic acid (PNA) dodecamers antisense to <jats:italic>CCND1<\/jats:italic> and <jats:italic>MYC<\/jats:italic> mRNAs were then extended from the N\u2010terminus of IGF1, followed by a chelator peptide, using Fmoc coupling for all residues. The cysteine thiols were cyclized on the solid support, either before or after PNA extension. This simplified synthetic approach allows preparation of a variety of multipeptide disulfide\u2010bridged PNA chimeras. A chelating peptide\u2010PNA chimera antisense to <jats:italic>MYC<\/jats:italic> mRNA was then labeled efficiently with Tc\u201099m, yielding a single product. Tissue distribution studies of antisense and mismatch chimeras at 4 h and 24 h after administration displayed modest accumulation in the liver and kidneys, with appreciable levels in tumors. This result enables testing of Tc\u201099m\u2010peptide\u2010PNA probes to image gene expression in tumors.<\/jats:p>","DOI":"10.1196\/annals.1281.015","type":"journal-article","created":{"date-parts":[[2004,1,30]],"date-time":"2004-01-30T01:18:50Z","timestamp":1075425530000},"page":"165-188","source":"Crossref","is-referenced-by-count":13,"title":["Imaging Oncogene Expression"],"prefix":"10.1111","volume":"1002","author":[{"given":"XIAOBING","family":"TIAN","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MOHAN R.","family":"ARUVA","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"PONUGOTI S.","family":"RAO","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"WENYI","family":"QIN","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"PAUL","family":"READ","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"EDWARD R.","family":"SAUTER","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MATHEW L.","family":"THAKUR","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ERIC","family":"WICKSTROM","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,1,24]]},"reference":[{"key":"e_1_2_9_2_2","first-page":"654","article-title":"Prolonged response to antisense cyclin D1 in a human squamous cancer xenograft model","volume":"6","author":"Sauter E.R.","year":"2000","journal-title":"Clin. 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