This review discusses the production of alpha-particle-emitting radionuclides in radioimmunotherapy. Radioimmunotherapy labeled with alpha-particle is expected to be very useful for the treatment of monocellular cancer (e.g. leukemia) and micrometastasis at an early stage, residual tumor remained in tissues after chemotherapy and tumor resection, due to the high linear energy transfer (LET) and the short path length in biological tissue of alpha particle. Despite of the expected effectiveness of alpha-particle in radioimmunotherapy, its clinical research has not been activated by the several reasons, shortage of a suitable a-particle development and a reliable radionuclide production and supply system, appropriate antibody and chelator development. Among them, the establishment of radionuclide development and supply system is a key factor to make an alpha-immunotherapy more popular in clinical trial. Alpha-emitter can be produced by several methods, natural radionuclides, reactor irradiation, cyclotron irradiation, generator system and elution. Due to the sharply increasing demand of 213Bi, which is a most promising radionuclide in radioimmunotherapy and now has been produced with reactor, the cyclotron production system should be developed urgently to meet the demand.
Alpha Particles ; Cyclotrons ; Drug Therapy ; Linear Energy Transfer ; Neoplasm Micrometastasis ; Neoplasm, Residual ; Radioimmunotherapy* ; Radioisotopes*

People are generally exposed to radiation from natural sources. Radon is the most important radiation source among natural sources. Radon is a naturally occurring, radioactive noble gas that is odorless and tasteless. Radon is normally found at very low levels in outdoor air and in drinking water from rivers and lakes but higher levels in indoor air in homes, schools, and office buildings, and in well water. When radon undergoes radioactive decay, it expels high-energy alpha particles. The alpha particle radiation dose from long-term exposure increases the chance of developing lung cancer. Radon is the second most important cause of lung cancer after smoking. There is no known threshold concentration below which radon exposure presents no risk. Even low concentrations of radon can result in a small increase in the risk of lung cancer. No study of the radon exposure-lung cancer association has been performed in Korea. What is needed is a large-scale prospective study of the association between residential radon exposure and lung cancer. The cumulative indoor radon exposure is an important environmental health hazard (carcinogen).
Alpha Particles ; Drinking Water ; Environmental Health ; Humans ; Korea ; Lakes ; Lung Neoplasms ; Radon ; Rivers ; Smoke ; Smoking ; Water

Radon is a naturally occurring radioactive material classified as a carcinogen by the World Health Organization, and is known to be the factor with the second-greatest impact on lung cancer after smoking. An association between radon and lung cancer has consistently been reported in epidemiological studies on mine workers and residents of homes with indoor radon exposure. However, associations between radon and other diseases, such as leukemia and thyroid cancer, have yet to be confirmed due to a lack of consistent research findings and biological relevance. Such associations are unlikely because there is a very low likelihood that organs other than the lungs are exposed to radon upon inhalation due to the short half-life of radon and its progeny and the low permeability of alpha rays. In spring 2018, the radon bed mattress incident occurred, leading to a spike of concern and interest among the public regarding the health effects of radiation exposure. This paper presents a description of radon exposure and its health effects based on the current literature and provides practical information based on health consultations experienced following the 2018 radon mattress incident.
Alpha Particles ; Epidemiologic Studies ; Half-Life ; Inhalation ; Leukemia ; Lung ; Lung Neoplasms ; Miners ; Permeability ; Radiation Exposure ; Radon ; Referral and Consultation ; Smoke ; Smoking ; Thyroid Neoplasms ; World Health Organization

Radionuclides are naturally occurring unstable atoms that undergo radioactive decay. There are ways of radioactive decay emitting different types of radiation based on their physical properties. Radiation for medical purposes include gamma rays, characteristic X-rays, negative and positive electrons, and alpha particles. Different from external radiotherapy, radionuclide therapy internally delivers therapeutic doses of radiation to the targeted tissue. Historically, P-32 orthophosphate was used for the management of myeloproliferative disorders. I-131 has been used for the treatment of hyperthyroidism as well as thyroid cancer for decades. It is one of the most commonly used therapeutic radionuclides in the current practice and its usefulness has been well established by selectively ablating thyroid tissue. For bone pain by osteoblastic metastases, phosphorus-32, strontium-89, samarium-153, or rhenium-186 could be effectively used in combination with narcotics. Another well known radionuclide therapy is I-131 MIBG for the palliation of patients with inoperable tumors of neural crest origin. In contrast to systemic administration of radioactive materials, local control of malignant tumors could be done by delivering radiation through an intratumoral or intraarterial route. In addition, radioactive skin patch or stent has a promising role in killing skin cancers, esophageal cancer, or malignant biliary strictures. Recently, I-131 or Y-90 conjugated with monoclonal antibodies increases the efficacy of radiation damage to lymphoma tissue employing the targeting effect of monoclonal antibodies. Likewise, radionuclide therapy in combination with gene therapy seems to be promising albeit tumor specific ways of gene delivery should be further investigated. Other possible candidates in radionuclide therapy are radioactive peptides and antisense oligonuclides.
3-Iodobenzylguanidine ; Alpha Particles ; Antibodies, Monoclonal ; Constriction, Pathologic ; Esophageal Neoplasms ; Gamma Rays ; Genetic Therapy ; Homicide ; Humans ; Hyperthyroidism ; Lymphoma ; Myeloproliferative Disorders ; Narcotics ; Neoplasm Metastasis ; Neural Crest ; Osteoblasts ; Peptides ; Phosphates ; Radioisotopes ; Radiotherapy ; Skin ; Skin Neoplasms ; Stents ; Thyroid Gland ; Thyroid Neoplasms

OBJECTIVETo investigate synergistic effect of bromocriptine (BCT) combining tumor necrosis factor-alpha (TNF-alpha) on reversing multidrug resistance in a nude mouse model of liver neoplasm.

METHODSHuman hepatocarcinoma cell line HepG(2) (HepG(2) group), drug resistant hepatocarcinoma cell line HepG(2)/adriamycin (HepG(2)/ADM group) and hepatocarcinoma cell line transfected with TNF-alpha gene HepG(2)/ADM/TNF (TNF group and BCT group) were injected into the liver of nude mice via orthotopic implantation to establish multidrug resistance model of liver neoplasm in vivo. All the mice were injected with 5-fluouracil + adriamycin + mitomycin in abdominal cavity for 7 d. The mice in BCT group was simultaneously given bromocriptine through gastric canal. Size and weight of the tumor were measured. Furthermore tumor histological character and growth of the nude mice was observed and its chemosensitivity was tested. MDR associated genes and proteins (MRP, LRP) of implanted tumors were detected by immunohistochemical staining and reverse transcriptive polymerase chain reaction (RT-PCR), and apoptosis rate of hepatocarcinoma cells was detected by TUNEL assay.

RESULTSThe nude mouse model of each cell line was all inoculated successfully. The tumor growth rate and weight were significantly different among groups (P < 0.05). After chemotherapy tumor growth inhibition rate was higher in BCT group (67%) compared to ADM and TNF groups (P < 0.01), and similar to HepG(2) group (54%). MDR1 and LRP mRNA could be detected in all groups, but TNF-alpha was detected only in TNF-alpha and BCT groups. Furthermore, MDR1 and LRP protein expression of tumors in TNF-alpha and BCT groups was low similar to HepG(2) group. The apoptosis rate of hepatocarcinoma cells was much higher in BCT group than in other groups (P < 0.05) with TUNEL assay.

CONCLUSIONSTNF-alpha gene can down-regulate the MDR associated genes and proteins expression for example MDR1, LRP, and lower its tumorgenesis. Moreover, bromocriptine can enhance the susceptibility of HepG(2)/ADM cells to cytotoxic drugs.

Animals ; Bromocriptine ; pharmacology ; Cell Line, Tumor ; Drug Resistance, Multiple ; drug effects ; genetics ; Drug Resistance, Neoplasm ; drug effects ; genetics ; Drug Synergism ; Female ; Humans ; Liver Neoplasms, Experimental ; metabolism ; therapy ; Male ; Mice ; Mice, Nude ; Multidrug Resistance-Associated Proteins ; biosynthesis ; genetics ; Neoplasm Transplantation ; Transfection ; Tumor Necrosis Factor-alpha ; genetics ; pharmacology ; Vault Ribonucleoprotein Particles ; biosynthesis ; genetics

OBJECTIVETo explore the mechanism of multidrug resistance of hepatocellular carcinoma induced by hypoxia and the potential role of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and multidrug resistance related genes.

METHODSHuman hepatocarcinoma cell lines HepG2 cells were exposed to hypoxia and were transfected by plasmid HIF-1 alpha/PCDNA3, respectively. The expressions of multidrug resistance gene (mdr1), multidrug resistance protein (MRP1), and lung resistance protein (LRP) gene at the mRNA and the protein levels in the above two groups were respectively analyzed by real-time fluorescent quantitative PCR and Western-blot technique.

RESULTSIn the hypoxia group, the expressions of mdr1, MRP1 and LRP were stepped up correlating to the degree of hypoxia, especially the prominent increase in the expression of MRP1. Furthermore, they were synchronous with the changes of the expression of HIF-1 alpha. Also the increased expression of mdr1, MRP1, and LRP gene was observed in transfected HepG2 cells by plasmid HIF-1 alpha/PCDNA3.

CONCLUSIONSResistance of hepatocellular carcinoma to chemotherapeutics could be induced by hypoxia. HIF-1 alpha may be critical to the upregulation of the expression of the related multidrug resistance genes induced by hypoxia. HIF-1 alpha and these related multidrug resistance genes could be potential molecular targets for reversing multidrug resistance of hepatocellular carcinoma.

Blotting, Western ; Carcinoma, Hepatocellular ; genetics ; Cell Hypoxia ; physiology ; Cell Line, Tumor ; Drug Resistance, Multiple ; physiology ; Drug Resistance, Neoplasm ; physiology ; Gene Expression Regulation, Neoplastic ; Genes, MDR ; genetics ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; biosynthesis ; genetics ; Lung Neoplasms ; genetics ; Multidrug Resistance-Associated Proteins ; biosynthesis ; genetics ; Polymerase Chain Reaction ; Transfection ; Vault Ribonucleoprotein Particles ; biosynthesis ; genetics