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Titolo:
Interferon-alpha-2b immunoconjugate for improving immunoscintigraphy and immunotherapy
Autore:
Pallela, VR; Rao, SP; Thakur, ML;
Indirizzi:
Thomas Jefferson Univ Hosp, Dept Radiol, Philadelphia, PA 19107 USA ThomasJefferson Univ Hosp Philadelphia PA USA 19107 elphia, PA 19107 USA
Titolo Testata:
JOURNAL OF NUCLEAR MEDICINE
fascicolo: 6, volume: 41, anno: 2000,
pagine: 1108 - 1113
SICI:
0161-5505(200006)41:6<1108:IIFIIA>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOMBINANT ALPHA-INTERFERON; TC-99(M)-LABELED MONOCLONAL-ANTIBODIES; GAMMA-INTERFERON; TUMOR UPTAKE; ENHANCEMENT; XENOGRAFTS; THERAPY; COMBINATION; IRRADIATION; RADIATION;
Keywords:
immoconjugate; interferon-monoclonal antibody conjugate; improving RIS and RIT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Thakur, ML Thomas Jefferson Univ Hosp, Dept Radiol, 1020 Locust St,Ste 359JAH, Philadelphia, PA 19107 USA Thomas Jefferson Univ Hosp 1020 Locust St,Ste 359 JAH Philadelphia PA USA 19107
Citazione:
V.R. Pallela et al., "Interferon-alpha-2b immunoconjugate for improving immunoscintigraphy and immunotherapy", J NUCL MED, 41(6), 2000, pp. 1108-1113

Abstract

A pretreatment with a single dose of an immunoconjugate (IC) that promisesto enhance tumor uptake and decrease liver uptake of radiolabeled monoclonal antibodies (MAbs) might be of use in radioimmunodetection and radioimmunotherapy (RIT). We have shown previously that an interferon (IFN)-MAb (1:1)immunoconjugate (IC) enhances tumor uptake by a factor of 2 or more and reduces river uptake by 50% in nude mice bearing human tumors. The aim of this study was to determine whether IFN modulates antigenic expression and to ascertain the most effective route of its administration, the optimal quantity to be administered, and the optimal duration of time to lapse between the administration of IC and the radiolabeled MAb. Methods: IFN-alpha-2b andanticarcinoembryonic antigen-F6 (IgG2a) MAb were conjugated (1:1), and F(ab')(2) of the MAb was labeled with (TC)-T-99m. Human colorectal tumors weregrown in nude mice by implanting 5 x 10(6) LS174T confluent cells grown inculture. Mice, 5 in each group, received 20 x 10(3) IU intravenously, intramuscularly, or intraperitoneally and 40 x 10(3), 60 x 10(3), and 80 x 10(3) IU intravenously 30 min before the intravenous administration of 25.9 MBq(TC)-T-99m/20 mu g F(ab')(2). Mice in the control groups received Tc-99m-F(ab')(2) but not the conjugate. Twenty-four hours later mice were killed and imaged, and tissues were removed for quantitative (percentage injected dose/g [% [D/g]) distribution of (TC)-T-99m. Results: in all conjugate-receiving mice, the tumor uptake was higher and the liver uptake was tower (P < 0.01) than that in the control mice with the exception of liver uptake, which was not significantly different in mice receiving 80 x 10(3) IU conjugate. The optimal results were apparent in mice pretreated with 40 x 10(3) IU conjugate in which tumor uptake was enhanced by a factor of 2.3 (4.8 +/- 0.5%ID/g versus 11 +/- 0.7 %ID/g; P < 0.01). The renal uptake remained unchanged, and the tumor-to-muscle ratios increased from 11.5 +/- 6.8 to 14.6 +/-3.9, and the tumor-to-blood ratios increased from 4.4 +/- 1.8 to 8.3 +/- 2.4. The liver uptake decreased from 9.5% +/- 1% to 5% +/- 1.6%. Results were attributed to enhanced tumor blood flow, increased antigenic expression, and blocking of hepatic nonspecific Fc receptors. Conclusion: A pretreatment with IFN-MAb conjugate is a worthwhile approach to consider in radioimmunoscintigraphy and RIT.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/21 alle ore 16:27:46