Current Radiopharmaceuticals - Volume 1, Issue 3, 2008

In this thematic issue of Current Radiopharmaceuticals the research and development in the field of internal radionuclide therapy with alpha-particle emitters is addressed. Targeted radionuclide therapy is a viable alternative to external beam radiation therapy, at least for some cancer forms, and can deliver selectively curative doses of radiation to cancer cells. The radiopharmaceuticals in vogue for these applications a Read More

Alpha-emitting radionuclides provide effective cell-killing properties and have been shown to be effective in cancer treatment. The number of different alpha emitters having suitable physical and chemical characteristics for applications in medicine is relatively few. Development and testing of new radiopharmaceuticals requires a reliable supply of alpha- emitters in high quality, with timely delivery, but at reasonable cost. Ap Read More

Targeted alpha therapy (TAT) is a promising approach for the treatment of cancer and infectious diseases. The availability of suitable alpha emitting isotopes in clinically relevant amounts is a main prerequisite for further development of TAT and its widespread clinical application. Several alpha emitting isotopes have been proven effective in preclinical studies and/or clinical trials, including 225Ac / 213Bi, 230U / 226Th, 227Th / 2 Read More

A review of the literature has been conducted on 211At-labeled compounds, which focuses on their in vitro and in vivo stability towards deastatination. In vivo stability is very important in 211At-labeled compounds being developed for treating human disease. Instability of the 211At-carbon bond found in many labeled compounds leads to release of [211At]astatide. Therefore, the review includes information from lite Read More

For the treatment of minimum residual diseases such micrometastases and residual tumor margins that remain after debulking of the primary tumor, targeted radiotherapy using radiopharmaceuticals tagged with α-particle-emitting radionuclides is very attractive. In addition to the their short range in tissue, which helps minimize harmful effects on adjacent normal tissues, α-particles, being high LET radiation, have sever Read More

Transfer of the gene encoding the noradrenaline transporter (NAT) into tumor cells rendered them amenable to dose dependent, [131I]meta-iodobenzylguanidine ([131I]MIBG) mediated cell kill. We have utilised the human telomerase component promoters (hTR and hTERT) to drive NAT gene expression specifically in tumor cells. Transfected cells were treated with benzylguanidine conjugated to the α-emitting radionuclid Read More

The radiobiological and radiochemical properties of radium-223 (223Ra, T1/2 = 11.4 d) render this alpha-emitting radionuclide promising for targeted cancer therapy. Together with its short-lived daughters, each 223Ra decay produces four alpha-particle emissions which enhance therapy effectiveness at the cellular level. In this paper, we review the recently published data reported for pre-clinical and clinical use of 223Ra Read More

A novel technology for preparing low dose rate alpha-radioimmunoconjugates has recently been developed based on the actinide radionuclide 227Th (T1/2=18.7 days). Thorium-227 has interesting properties that can be exploited in radioimmunotherapy: (1) it can be conjugated in stable fashion to antibodies using bifunctional DOTA; (2) it can be produced in virtually unlimited amounts with current technology; (3) it has a Read More

Poor prognosis of gastric cancer patients is based on early tumor cell dissemination into the peritoneal cavity. Therefore, efficient therapies for disseminated tumor cells are urgently needed. Patients suffering from diffuse-type gastric cancer occasionally express a mutant variant of E-cadherin lacking exon 9 (d9-E-cad). A monoclonal antibody (d9MAb) labelled with 213Bi specifically targeting d9- E-cad, therefore is a pr Read More

This article is based on results from four published experimental studies. I: Three HER2 overexpressing cell lines were exposed to α-particles from the HER2 binding affibody molecule 211At- (ZHER2:4)2. The sensitivity differed; SKOV3 was resistant, SKBR3 intermediate and BT474 sensitive. The differences were unexpected since it is assumed that different types of cells should have a similar sensitivity to high-LET radiation. II: Eff Read More

Bismuth-213 (213Bi) (physical half-life 46 min) is a beta-emitter (97%) and an alpha-emitter (3%) which decays to short lived alpha-emitter Polonium-213 and could therefore be used as a generator of alpha particles with the energy of around 8 MeV. 213Bi has been successfully used during the last decade in both clinical and pre-clinical work for radioimmunotherapy (RIT) of cancer with 213Bi-labeled monoclonal antib Read More

This paper reviews the journey taken by the Centre for Experimental Radiation Oncology from bench to bedside in the development of targeted alpha therapy (TAT) for metastatic melanoma. The alpha-immunoconjugate (AIC) 213Bi-cDTPA-9.2.27 (AIC) has been prepared and investigated for stability, labelling yield, toxicity, cytotoxicity and preclinical and clinical response. Preclinical studies gave high labelling efficiency and hig Read More

Among radionuclides usable for tumor therapy, α-particle emitters are characterized by a very high linear energy transfer (LET) resulting in a larger number of ionizations in a range corresponding to a cell diameter. Therefore, they can determine a stronger therapeutic effect compared to low LET β-particle emitters, producing their ionizations in a range up to many millimeters. In fact, because the distance between the two Read More