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Titolo:
Avidin-dendrimer-(1B4M-Gd)(254): A tumor-targeting therapeutic agent for gadolinium neutron capture therapy of intraperitoneal disseminated tumor which can be monitored by MRI
Autore:
Kobayashi, H; Kawamoto, S; Saga, T; Sato, N; Ishimori, T; Konishi, J; Ono, K; Togashi, K; Brechbiel, MW;
Indirizzi:
Kyoto Univ, Dept Nucl Med & Diagnost Imaging, Kyoto 6068507, Japan Kyoto Univ Kyoto Japan 6068507 & Diagnost Imaging, Kyoto 6068507, Japan Otsu Municipal Hosp, Dept Radiol, Otsu, Shiga 5200804, Japan Otsu Municipal Hosp Otsu Shiga Japan 5200804 , Otsu, Shiga 5200804, Japan Kyoto Univ, Inst Res Reactor, Osaka 5900494, Japan Kyoto Univ Osaka Japan 5900494 v, Inst Res Reactor, Osaka 5900494, Japan NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 adiat Oncol Branch, NIH, Bethesda, MD 20892 USA
Titolo Testata:
BIOCONJUGATE CHEMISTRY
fascicolo: 4, volume: 12, anno: 2001,
pagine: 587 - 593
SICI:
1043-1802(200107/08)12:4<587:AATTAF>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
MONOCLONAL-ANTIBODY; CONTRAST AGENTS; DENDRIMER; AVIDIN; BIODISTRIBUTION; ACCUMULATION; FLEXIBILITY; CLEARANCE; GROWTH; CANCER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Kobayashi, H Kyoto Univ, Grad Sch Med, Dept Diagnost & Intervent Imagiol, Hitachi Med Co, Kyoto 6068507, Japan Kyoto Univ Kyoto Japan 6068507 Med Co, Kyoto 6068507, Japan
Citazione:
H. Kobayashi et al., "Avidin-dendrimer-(1B4M-Gd)(254): A tumor-targeting therapeutic agent for gadolinium neutron capture therapy of intraperitoneal disseminated tumor which can be monitored by MRI", BIOCONJ CHE, 12(4), 2001, pp. 587-593

Abstract

Peritoneal carcinomatosis is a late stage in cancer progress, for which noeffective therapeutic modality exists. Targeting therapeutic agents to disseminated lesions may be a promising modality for treating peritoneal. carcinomatosis. Gadolinium (Gd-157,Gd-155) is known to generate Auger and internal conversion electrons efficiently by irradiation with a neutron beam. Auger electrons from neutron-activated Gd(III) are strongly cytotoxic, but only when Gd(III) atoms have been internalized into the cells. In the presentinvestigation, we have developed a quickly internalizing turner-targeting system to deliver large quantities of Gd(III) atoms into tumor cells to generate the Auger emission with an external neutron beam. Simultaneously, onewould be able to image its biodistribution by MRI with a shortened T1 relaxation time. Avidin-G6-(1B4M-Gd)(254) (Av-G6Gd) was synthesized from generation-6 polyamidoamine dendrimer, biotin, avidin, and 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M). The Av-G6Gd was radiolabeled with Cd(III) doped with Gd-153. All of the 1B4M's on the conjugate were fully saturated with Gd(III) atoms. An in vitro internalization study showed that Av-G6Gd accumulated and was internalized into SHIN3 cells (ahuman ovarian cancer) 50- and 3.5-fold greater than Gd-DTPA (Magnevist) and G6-(1B4M-Gd)(256) (GGGd). In addition, accumulation of Gd(III) in the cells was detected by the increased signal on T1-weighted MRI. A biodistribution study was performed in nude mice bearing intraperitoneally disseminated SHINS tumors. Av-G6Gd showed specific accumulation in the SHIN3 tumor (103%ID/g) 366- and 3.4-fold greater than Gd-DTPA (0.28% ID/g, p < 0.001) and G6Gd (30% ID/g, p < 0.001) 1 day after i.p. injection. Seventy-eight percentof the tumor-related radioactivity of Av-G6Gd in the SHINS tumor was located inside the cells. The SHIN3 tumor-to-normal tissue ratio was greater than 17:1 in all organs and increased up to 638:1 at 1 day after i.p. injection. In conclusion, a sufficient amount (162 ppm) of Av-G6Cd was accumulated and internalized into the SHINS cells both in vitro and in vivo to kill thecell using Gd-157/155 With external irradiation with an appropriate neutron beam while monitoring with MRI. Thus, Av-G6Gd may be a promising agent for Gd neutron capture therapy of peritoneal carcinomatosis. This reagent also has the potential to permit monitoring of its pharmacokinetic progress with MRI.

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Documento generato il 09/07/20 alle ore 17:08:10