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Titolo:
Noninvasive monitoring of gene transfer using a reporter receptor imaged with a high-affinity peptide radiolabeled with Tc-99m or Re-188
Autore:
Zinn, KR; Buchsbaum, DJ; Chaudhuri, TR; Mountz, JM; Grizzle, WE; Rogers, BE;
Indirizzi:
Univ Alabama, Dept Radiol, Div Nucl Med, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 v Nucl Med, Birmingham, AL 35294 USA Univ Alabama, Dept Radiat Oncol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 diat Oncol, Birmingham, AL 35294 USA Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA Univ Alabama Birmingham AL USA 35294 ept Pathol, Birmingham, AL 35294 USA
Titolo Testata:
JOURNAL OF NUCLEAR MEDICINE
fascicolo: 5, volume: 41, anno: 2000,
pagine: 887 - 895
SICI:
0161-5505(200005)41:5<887:NMOGTU>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON-EMISSION-TOMOGRAPHY; POTENTIAL IMAGING AGENT; IN-VIVO; BINDING PEPTIDES; VIRAL-INFECTION; CANCER-THERAPY; LIVING MAMMALS; EXPRESSION; PET; PROLIFERATION;
Keywords:
imaging; gene transfer; somatostatin receptor; peptide; Tc-99m; Re-188;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Zinn, KR Univ Alabama, Dept Radiol, Div Nucl Med, BDB 11,1530 3rd Ave S, Birmingham, AL 35294 USA Univ Alabama BDB 11,1530 3rd Ave S Birmingham AL USA 35294 94 USA
Citazione:
K.R. Zinn et al., "Noninvasive monitoring of gene transfer using a reporter receptor imaged with a high-affinity peptide radiolabeled with Tc-99m or Re-188", J NUCL MED, 41(5), 2000, pp. 887-895

Abstract

Gene therapy protocols require better modalities to monitor the location and level of transferred gene expression. One potential in vivo mechanism toassess gene expression would be to image the binding of a radiolabeled peptide to a reporter receptor that is expressed in targeted tissues. This concept was tested in a tumor model using a replication-incompetent adenoviralvector encoding the human type 2 somatostatin receptor (Ad5-CMVhSSTr2), Expression of the hSSTr2 reporter was imaged using a radiolabeled, somatostatin-avid peptide (P829). Methods: Bilateral subcutaneous A427 tumor xenografts were established on the flanks of athymic nude mice. These human-origin,non-small cell lung tumors are normally negative for hSSTr2 expression. One tumor was injected directly with Ad5-CMVhSSTr2, whereas the second tumor was injected directly with a control Ad5 vector. The mice were injected intravenously 48 h later with P829 peptide that was radiolabeled to high specific activity with Tc-99m (half-life, 6 h) or Re-188 (half-life, 17 h). Tumors were frozen and evaluated for somatostatin receptor expression using fluorescein-labeled somatostatin. Results: The accumulation of radiolabeled P829 in hSSTr2-expressing tumors was easily visualized by gamma camera imaging 3 h after injection. Imaging region of interest analyses and biodistribution studies confirmed a 5- to 10-fold greater accumulation of both radiolabeled P829 peptides in the Ad5-CMVhSSTr2-injected tumors versus control tumors injected with control Ad5 vectors. Ad5-CMVhSSTr2-injected tumors accumulated 2.5-3.8 percentage injected dose per gram 3 h after injection. Only Ad5-CMVhSSTr2-injected tumors expressed somatostatin receptors, as determinedby immunohistochemistry. Conclusion: These studies show the feasibility ofimaging a Tc-99m-labeled peptide's binding to a reporter receptor after invivo gene transfer to tumor cells. The Re-188-labeled peptide worked equally well for this imaging approach and offers the additional advantage of energetic beta decay with potential therapeutic efficacy. Tc-99m and Re-188 are generator produced, an advantage for widespread availability and low cost, and both radioisotopes can be imaged with existing, high-resolution modalities. There is great potential for using Tc-99m-labeled peptides for imaging gene transfer with the hSSTr2 reporter receptor, especially when the reporter correlates with the expression of therapeutic genes that can be included simultaneously in the gene therapy vector.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/08/20 alle ore 01:30:48