Nerve sparing radical prostatectomy

State-of-the-art external beam radiotherapy

Seed Brachytherapy

Patient Information For High Dose Rate Hdr Prostate Brachytherapy

Hormonal therapy

Prostatic cryotherapy

Systemic chemotherapy

Radioactive intravenous Strontium

Access to state-of-the-art clinical trial

Patient Information for Radiotherapy

Targeted Alpha Therapy

Pain relief for metastatic bone disease

Overview of TAT for prostate cancer

Targeted alpha therapy (TAT) is an emerging therapeutic modality wherein a labeled protein selectively targets cancer cells and delivers a lethal payload, which can kill cancer cells in transit or pre-angiogenic cell clusters. Prostate cancer is the second most common cancer in men. In spite of the most aggressive therapy, a significant percentage of men die of metastatic disease, which usually spreads in the early stages. Currently, therapy is limited to chemotherapy and hormone therapy, both of which show clinical improvement but long-term survival is uncertain. a radiation emitted by the decay of certain radioisotopes is very energetic but has a range of only a few cell diameters. As such, a radiation is markedly superior for destroying cancer cells and minimizing damage to distant normal tissues.

The current interesting a-emitting radionuclides in radioimmunotherapy include ¹⁴⁹Tb, ²¹¹At, ²¹²Bi, ²¹³Bi and ²²⁵Ac. These radioisotopes are different in half-life, energy, branching ratio and range. a-particles have several advantages over b-particles:

·        They cause DNA damage that is not easily repaired by the cell due to their very high LET (100 keV/mm)

·        Their cytotoxicity is not affected by oxygen

·        They are much more cytotoxic, requiring as few as 6 or 7 disintegrations for internalized a-particles and ~25 disintegrations for surface-bound a-emitters to kill a cell.

The progression of prostate cancer from a hormone-naïve primary to increasingly androgen-independent metastatic disease is associated with a number of molecular and genetic changes. These changes can affect the expression of specific antigens on the cell surface. Targeting cancer surface antigens with targeting molecules is a new and promising area of research. Modern advances in the field of targeted therapy hold the promise of providing the clinical urologist/oncologist with new tools to fight prostate cancer.

a-particle therapy has been successful for use in single-cell disorders and micrometastatic carcinomas in which rapid targeting to cancer cells is possible. Recent preclinical studies with different targeting molecules labelled with Bi-213 show that TAT is highly cytotoxic to prostate cancer cells in vitro, and can inhibit tumour growth in animal models.

TAT, using antibodies or proteins against tumour-associated antigens is an active area of ongoing investigation at both the experimental and the clinical levels.  TAT may have a promising future in the control of prostate cancer at the minimal residual disease stage and with hormone-refractory disease.

Publications

In vitro and preclinical targeted alpha therapy for melanoma, breast, prostate and colorectal cancers. B J Allen, S Rizvi, Y Li, Z Tian, M Ranson. Critical Rev Oncology/Haematology, 2001: 39:39-146.

In vitro and preclinical studies of targeted alpha therapy of human prostate cancer with Bi-213 labeled J591 antibody against the prostate specific membrane antigen.  Y Li, Z Tian, SMA Rizvi, N H Bander, B J Allen, Prostate Cancer and Prostatic Disease, 2002: 5; 36-46.

²¹³Bi-PAI2 conjugate selectively induces apoptosis in PC3 metastatic prostate cancer cell line and shows anti-cancer activity in a xenograft animal model. Y Li, S Rizvi, M Ranson, B J Allen. Brit J Cancer, 2002: 86(7); 1197-1203.

Targeted alpha therapy of prostate cancer. Allen BJ, Li Y, Rizvi SMA, Russell PJ. In: Prostate Cancer Methods and Protocols. Ed Russell PJ, Jackson P, Kingsley EA. Humana Press, 2003: 335-359.

Cytotoxicity of human prostate cancer cell lines in vitro and induction of apoptosis using ²¹³Bi-Herceptin alpha conjugate. Li Y, Cozzi PJ, Qu CF, Zhang DY, Rizvi SMA, Raja C, Allen BJ. Cancer Letters 2004: 205; 161-171.

Antigenic expression of human prostate cancer cell lines and primary prostate cancer sections for in vitro multiple targeted alpha therapy with Bi-213 conjugates. Li y, Rizvi SMA, Brown J, Cozzi PJ, Qu CF, Ow KT, Tam PN, Perkins AC, Russell PJ, Allen BJ. ,Int J Radiat Oncol Biol Phys, 2004: 60/3; 896-908.

Targeted alpha therapy for control of micrometastatic prostate cancer. Li Y, Russell P, Allen BJ. Expert Review of Anticancer Therapy. 2004: 4(3); 459-468

Targeted alpha therapy for cancer. Allen BJ, Raja C, Rizvi S, Li Y, Tsui W, Zhang S, Song E, Qu Chang Fa, Kearlsey J, Graham P, Thompson J. Phys Med Biol 2004: 49;3703-3712.