Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Radioimmunotherapy with the alpha-emitter Astatine-211

For more infromation please visit our website.

The overall goal of this project is to develop clinically feasible targeted therapies by use of the short-range high-efficiency alpha-emission from 211At, conjugated to tumour-binding ligands for application in disseminated sub-clinical residual cancers.

The majority of patients succumbing from malignancy do so due to disseminated disease. In general, the large, solid tumor groups cannot be cured when dissemination can be visualized. Thus, as a complement to local treatment, surgery and/or radiotherapy, effective systemic therapy is urgently needed. With adjuvant systemic chemotherapy, i.e. against subclinical disease, less than 30% of those having microscopic disease are cured. We attempt to develop therapeutics based on targeted irradiation of microscopic tumors with alpha-emitting radionuclides. This systemic radiation treatment modality may be curative for situations where current therapies fail.

High-LET alpha-emitters offer significant advantages in the treatment of micrometastatic disease. The energy deposited along the track of an alpha-particle is ~500 times higher than for electrons, making the alpha-particles highly radiotoxic. For example, it requires only 1-5 alpha-particle passages through a cancer cell's nucleus to inactivate it, while several thousand electrons are required for the same level of cell kill. This is extremely attractive for single cells, or micrometastases where the amount of targeting may be small owing to a limited number of antigens per cell. Another advantage of alphas is the very short particle range (< 70 µm), which conforms to micrometastases and spares surrounding normal tissue.

Ongoing projects are:

* Phase I trial with 211At-MX35 F(ab’)2 against ovarian cancer
* Animal studies of 211At-labelled mAb for prostate cancers
* Development of novel pre-targeting procedures for 211At
* Tumour response and risk organ's toxicity in vivo for 211At
* Estimation of the relative biological effectiveness, RBE in vivo
* Dosimetric and biokinetic models for 211At labelled molecules in man

Publications

Lindegren S, Skarnemark G, Jacobsson L, Karlsson B. Chloramine-T in high-specific-activity radioiodination of antibodies using N-succinimidyl-3-(trimethylstannyl)benzoate as an intermediate. Nucl Med Biol. 25: 659-665,1998

Palm S, Bäck T, Claesson I, Delle U, Hultborn R, Jacobsson L, Köpf I and Lindegren S. Effects of the alpha-particle emitter At-211 and low-dose-rate gamma-radiation on the human cell line Colo-205 as studied with a growth assay. Anticancer Res. 18: 1671-1676,1998

Andersson H, Lindegren S, Bäck T, Jacobsson L, Leser G, Horvath G. Biokinetics of the monoclonal antibodies Mov 18, OV 185 and OV 197 labelled with 125I according to the m-MeATE method of the iodogen method in nude mice with ovarian cancer xenografts. Acta Oncol. 38: 323-328,1999

Andersson H, Lindegren S, Bäck T, Jacobsson L, Leser G, Horvath G. Radioimmunotherapy of nude mice with intraperitoneally growing ovarian cancer xenograft utilizing 211At-labelled monoclonal antibody Mov18. Anticancer Res. 20: 459-462,2000

Palm S, Andersson H, Bäck T, Claesson I, Delle U, Hultborn R, Jacobsson L, Köpf I and Lindegren S. In vitro effects of free 211At, 211At-albumin, and 211At-monoclonal antibody compared to external photon irradiation on two human cancer cell lines. Anticancer Res. 20: 1005-1012,2000

Andersson H, Lindegren S, Bäck T, Jacobsson L, Leser G, Horvath G. The curative and palliative potential of the monoclonal antibody Mov18 labelled with 211At in nude mice with intraperitoneally growing ovarian cancer xenografts – a long term study. Acta Oncol. 2000;39(6):741-5

Palm S, Andersson H, Bäck T, Claesson I, Delle U, Hultborn R, Jacobsson L, Köpf I and Lindegren S. Cell growth kinetics of two human cancer cell lines irradiated with astatine-211 and gamma-radiation. Anticancer Res. 2000 May-Jun;20(3A):1807-12

Palm S and Jacobsson L.. Dosimetrical considerations in astatine-211 radioimmunotherapy. In: Therapeutic Applications of Radiopharmaceuticals.
Proceedings of an international seminar held in Hyderabad, India, 18-22 January, 1999. IAEA-Tecdoc 1228. International Atomic Energy Commission, Vienna, 310-319, 2001

Andersson H, Palm S, Lindegren S, Bäck T, Jacobsson L, Leser G, Horvath G. Comparison of the therapeutic efficacy of 211At- and 131I-labelled monoclonal antibody Mov18 in nude mice with intraperitoneally growth of human ovarian cancer. Anticancer Res. 2001 Jan-Feb;21(1A):409-12.

Lindegren S, Andersson H, Bäck T, Jacobsson L, Karlsson B, Skarnemark G. High-efficiency astatination of antibodies using N-iodosuccinimide as the oxidising agent in labelling of N-succinimidyl 3-(trimethylstannyl) benzoate. Nucl Med Biol. 2001 Jan;28(1):33-9.

Lindegren S, Bäck T, Jensen HJ. Dry-distillation of astatine-211 from irradiated bismuth targets: a time-saving procedure with high recovery yields.
Appl Radiat Isot. 2001 Aug;55(2):157-60.

Andersson H, Palm S, Lindegren S, Back T, Jacobsson L, Leser G, Horvath G.
Comparison of the therapeutic efficacy of 211At- and 131I-labelled monoclonal antibody MOv18 in nude mice with intraperitoneal growth of human ovarian cancer.
Anticancer Res. 2001 Jan-Feb;21(1A):409-12.

Lindegren S, Andersson H, Jacobsson L, Back T, Skarnemark G, Karlsson B.
Synthesis and biodistribution of 211At-labeled, biotinylated, and charge-modified poly-L-lysine: evaluation for use as an effector molecule in pretargeted intraperitoneal tumor therapy.
Bioconjug Chem. 2002 May-Jun;13(3):502-9.

Stig Palm, Tom Bäck, Ingela Claesson, Ulla Delle, Ragnar Hultborn, Sture Lindegren and Lars Jacobsson
Single-cell irradiation from At-211 labeled C215 monoclonal antibody: improved estimates of radiosensitivity from measurements on cellular uptake and retention
Anticancer Res. 23, 1219-1222, 2003.

Sture Lindegren, Börje Karlsson, Lars Jacobsson, Håkan Andersson, Ragnar Hultborn and Gunnar Skarnemark
At-211 labelled and biotinylated effector molecules for pretargeted radioimmunotherapy using poly-L-and poly-D-Lysine as multicarriers
Clinical Cancer Research, 9, 3873-3879, 2003

Håkan Andersson, Jörgen Elgqvist, György Horvath, Ragnar Hultborn, Lars Jacobsson, Holger Jensen, Börje Karlsson, Sture Lindegren, and Stig Palm
Astatine-211 labeled antibodies for treatment of disseminated ovarian cancer: an overview of results in an ovarian tumor model
Clinical Cancer Research, 9, 3914-3921, 2003

Palm S, Humm JL, Rundqvist R, Jacobsson L.
Microdosimetry of astatine-211 single-cell irradiation: role of daughter polonium-211 diffusion.
Med Phys. 2004 Feb;31(2):218-25.

Jörgen Elgqvist, Peter Bernhardt, Ragnar Hultborn, Börje Karlsson, Sture Lindegren, Elisabeth Warnhammar and Lars Jacobsson
Myelotoxicity and RBE of 211At-conjugated monoclonal antibodies compared with 99mTc-conjugated monoclonal antibodies and 60Co irradiation in nude mice.
J Nucl Med. 2005 Mar;46(3):464-71.

Back T, Andersson H, Divgi CR, Hultborn R, Jensen H, Lindegren S, Palm S, Jacobsson L. 211At Radioimmunotherapy of Subcutaneous Human Ovarian Cancer Xenografts: Evaluation of Relative Biologic Effectiveness of an {alpha}-Emitter In Vivo.
J Nucl Med. 2005 Dec;46(12):2061-7.

Elgqvist J, Andersson H, Back T, Hultborn R, Jensen H, Karlsson B, Lindegren S, Palm S, Warnhammar E, Jacobsson L
Therapeutic Efficacy and Tumor Dose Estimations in Radioimmunotherapy of Intraperitoneally Growing OVCAR-3 Cells in Nude Mice with 211At-Labeled Monoclonal Antibody MX35.
J Nucl Med. 2005 Nov;46(11):1907-15.

Elgqvist J, Andersson H, Back T, Claesson I, Hultborn R, Jensen H, Johansson BR, Lindegren S, Olsson M, Palm S, Warnhammar E, Jacobsson L.
Alpha-radioimmunotherapy of intraperitoneally growing OVCAR-3 tumors of variable dimensions: Outcome related to measured tumor size and mean absorbed dose.
J Nucl Med. 2006 Aug;47(8):1342-50.

Elgqvist J, Andersson H, Bernhardt P, Back T, Claesson I, Hultborn R, Jensen H, Johansson BR, Lindegren S, Olsson M, Palm S, Warnhammar E, Jacobsson L.
Administered activity and metastatic cure probability during radioimmunotherapy of ovarian cancer in nude mice with 211At-MX35 F(ab')(2).
Int J Radiat Oncol Biol Phys. 2006 Nov 15;66(4):1228-37.

Elgqvist J, Andersson H, Back T, Claesson I, Hultborn R, Jensen H, Lindegren S, Olsson M, Palm S, Warnhammar E, Jacobsson L.
Fractionated radioimmunotherapy of intraperitoneally growing ovarian cancer in nude mice with 211At-MX35 F(ab')(2): therapeutic efficacy and myelotoxicity.
Nucl Med Biol. 2006 Nov;33(8):1065-72. .

Palm A, Bäck T, Claesson I, Danielsson A,Elgqvist J, Frost S, Hultborn R, Jensen H, Lindegren S, Jacobsson L
Therapeutic Efficacy of Astatine-211–Labeled Trastuzumab on
Radioresistant SKOV-3 Tumors in Nude Mice
Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):572-9

Dissertations

Palm S. In vitro effects and microdosimetry of astatine-211 for tumour therapy. PhD thesis. Göteborg University (1999).

Andersson H. Radioimmunotherapy of experimental ovarian cancer with astatine-211 – a model for consolidation treatment in women. PhD thesis. Göteborg University (2000)

Lindegren S
Astatine-211 and iodine conjugates: Radiohalogenation and preclinical pharmacokinetics for targeted and pretargeted radioimmunotherapy
PhD thesis, 2002

Elgqvist J
Astatine-211 Radioimmunotherapy of Ovarian Cancer
Therapeutic Efficacy, Myelotoxicity, and Radiation Dosimetry in an Animal Model

Kontaktinformation

Avdelningen för Radiofysik

Gula stråket 2B, Sahlgrenska Universitetssjukhuset, 413 45, Göteborg

Besöksadress:
Radiofysikhuset, Sahlgrenska Universitetssjukhuset

Sidansvarig: Johan Spetz|Sidan uppdaterades: 2015-08-03
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?