In vitro and preclinical targeted alpha therapy for melanoma, breast, prostate and colorectal cancers

被引:30
作者
Allen, BJ
Rizvi, S
Li, Y
Tian, Z
Ranson, M
机构
[1] St George Canc Care Ctr, Ctr Expt Radiat Oncol, Kogarah, NSW 2219, Australia
[2] Univ Wollongong, Ctr Expt Radiat Oncol, Wollongong, NSW 2500, Australia
[3] Univ New S Wales, Ctr Expt Radiat Oncol, Kensington, NSW 2033, Australia
关键词
targeted alpha therapy; in vitro; preclinical; melanoma; breast cancer; prostate cancer; colorectal cancer; monoclonal antibody; plasimogen activator inhibitor type 2;
D O I
10.1016/S1040-8428(01)00113-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Targeted alpha therapy (TAT) can inhibit the growth of micrometastases by, selectively killing isolated and preangiogenic clusters of cancer cells. The alpha emitting radioisotopes Tb-149 and Bi-213 were chelated to cancer specific monoclonal antibodies to form alpha-immunoconjugates (AIC) against melanoma, leukaemia, prostate and colorectal cancer, and to the plasminogen activator inhibitor type-2 (PAI2) to form alpha-PAI2 (API) against breast and prostate cancer. These conjugates were found to be highly stable, specific and cytotoxic in vitro. Melanoma and breast cancer tumour growth was observed in nude mouse models for untreated controls and non-specific AIC/API at 2 days post-subcutaneous inoculation of cancer cells. Complete inhibition of melanoma and breast cancer growth was found for local injections of AIC and API, respectively. Intra-lesional TAT of established melanoma showed that all melanomas regressed with 100 mu Ci injections of AIC. These results point to the potential application of local and systemic TAT in the management of metastatic cancer. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:139 / 146
页数:8
相关论文
共 33 条
[1]  
ABE O, 1992, LANCET, V339, P71
[2]  
Allen BJ, 1999, NUCL MED COMMUN, V20, P205
[3]   Alpha- and beta-emitting radiolanthanides in targeted cancer therapy: The potential role of terbium-149 [J].
Allen, BJ ;
Blagojevic, N .
NUCLEAR MEDICINE COMMUNICATIONS, 1996, 17 (01) :40-47
[4]  
ALLEN BJ, 1999, AUST RADIOL, V4, P43
[5]  
ALLEN BJ, 1999, P 6 INT C RAD DOS MA, P392
[6]   AT-211 RADIOCOLLOID THERAPY - FURTHER OBSERVATIONS AND COMPARISON WITH RADIOCOLLOIDS OF P-32, DY-165, AND Y-90 [J].
BLOOMER, WD ;
MCLAUGHLIN, WH ;
LAMBRECHT, RM ;
ATCHER, RW ;
MIRZADEH, S ;
MADARA, JL ;
MILIUS, RA ;
ZALUTSKY, MR ;
ADELSTEIN, SJ ;
WOLF, AP .
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 1984, 10 (03) :341-348
[7]   IMMUNOCHEMICAL AND BIOSYNTHETIC ANALYSIS OF MONOCLONAL ANTIBODY-DEFINED MELANOMA-ASSOCIATED ANTIGEN [J].
BUMOL, TF ;
CHEE, DO ;
REISFELD, RA .
HYBRIDOMA, 1982, 1 (03) :283-292
[8]   EXPERIENCE WITH RADICAL PROSTATECTOMY AND RADIATION-THERAPY FOR LOCALIZED PROSTATE-CANCER AT A VETERANS AFFAIRS MEDICAL-CENTER [J].
FOWLER, JE ;
BRASWELL, NT ;
PANDEY, P ;
SEAVER, L .
JOURNAL OF UROLOGY, 1995, 153 (03) :1026-1031
[9]  
GODDU SM, 1994, J NUCL MED, V35, P303
[10]   Pharmacokinetics and biodistribution of recombinant human plasminogen activator inhibitor type 2 (PAI 2) in control and tumour xenograft-bearing mice [J].
Hang, MTN ;
Ranson, M ;
Saunders, DN ;
Liang, XM ;
Bunn, CL ;
Baker, MS .
FIBRINOLYSIS & PROTEOLYSIS, 1998, 12 (03) :145-154