Radiopharmaceuticals As Therapeutic Agents in Medical Care and Treatment
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FEATURES Radiopharmaceuticals as therapeutic agents in medical care and treatment A new IAEA research programme assists countries interested in the use of improved radiopharmaceuticals for medical therapy by Hernan l adiation applications in medical research, healthy cells. Over the past several years, several Vera-Ruiz care, and treatment today are being used to help types of RPTs with special properties, including millions of patients throughout the world. compounds for labelling monoclonal antibodies, Perhaps most widely known are diagnostic have been used in animal and human clinical applications in the field of nuclear medicine, trials with promising results. which has seen significant expansion over the The modern trend in radiopharmaceutical re- past two decades. Such applications typically search for oncology is the development of RPTs employ radionuclides as tracers to aid in diag- that may be said to be tumour-seeking and nosing or studying medical conditions. lodine- tumour-specific. In therapeutic radiopharma- 131, for example, is effective in locating brain ceutical applications—unlike the case of exter- tumours, and in determining liver and thyroid nal radiation therapy where the radiation from an activity, and technetium-99m is a common agent external sealed radioactive source is focused on for imaging studies. the site to be irradiated—the product is admin- Other radiation applications are directed at istered to the patient orally or intravenously and treatment of serious disease, typically cancers. is selectively taken up or localized in the site to These include the well-known use of cobalt-60 be irradiated. Suitable agents have to be des- in cancer therapy, for example. Traditionally, igned to exploit the metabolic and biological other radionuclides, including iodine-131, phos- characteristics of tumours, so as to guide the phorus-32, and strontium-89, were used in the RPT and ensure proper localized treatment. fields of oncology, endocrinology, and rheuma- Among the promising RPTs being reported tology. The incorporation of more radionuclides in the medical literature are rhenium-186 and into the armamentarium of medical therapy dur- samarium-153. Both can be produced in research ing the last 30-40 years, however, has been slow reactors available in many countries. for a variety of reasons. In light of growing medical interest in the use In recent years, however, the medical com- of RPTs, and to foster continuing research in this munity has seen a renaissance of therapeutic field, the IAEA initiated a co-ordinated research radiation applications, particularly of strontium- programme in early 1993. This programme com- 89 for metastatic bone pain. The change has plements ongoing IAEA activities, largely come about largely through advances over the through its technical co-operation programme, past decade in the radiopharmaceutical industry, designed to assist countries in developing in- the greater availability of radionuclides with im- digenous capabilities and expertise in the prod- proved nuclear and chemical characteristics for uction of radionuclides for medical and in- medical uses, and encouraging results from clini- dustrial uses. cal studies on uses of radiopharmaceuticals for The research programme's objectives are to therapy. optimize the production of therapeutic radio- Radiopharmaceuticals used as therapeutic pharmaceuticals in research reactors, particular- agents (frequently known as RPTs) are designed ly taking into account the characteristics of reac- to deliver high doses of radiation to selected tors operating in developing countries. It also malignant sites in target organs or tissues, while will seek to further develop protocols for radio- minimizing the radiation doses to surrounding labelling and quality control. Countries from Africa, Asia and the Pacific, and Latin America Mr Vera-Ruiz is a senior officer in the IAEA Division of are participating in the work. Separately, the Physical and Chemical Sciences. IAEA also is implementing a co-ordinated re- 24 IAEA BULLETIN, 1/1993 FEATURES search programme on therapeutic applications of Beta emitters: radionuclides in patients with malignant metas- tases in bones. Radionuclide Half-life Maximum energy This article presents a brief selective over- (megavolts) view of some of the latest developments in the Phosphorus-32 14.3 days 1.71 production and preparation of RPTs, specifically Strontium-89 50.5 days 1.46 those being evaluated for the palliation of pain in Yttrium-90 2.7 days 2.27 bone cancers. Iodine-131 8.0 days 0.606 Dysprosium-165 2.3 hours 1.34 Samarium-153 1 .95 days 0.80 Selection of suitable radionuclides Holmium-166 1.1 day 1.6 Rhenium-186 89.3 hours 1.07 For therapeutic purposes, the selection of a Rhenium-188 1 7.0 hours 2.11 suitable radionuclide for a specific application Copper-67 2.4 days 0.57 takes into account a number of factors. These include the physical characteristics of the radio- nuclide itself, mainly the type and energy of the Auger emitters: radiation emitted and the radionuclide's half life, Radionuclide Half-life and the exact location of the target area to be lodine-123 13.3 hours treated. lodine-125 59.7 days The rationale or strategy in RPT is to deposit Mercury-197 2.7 days the greatest amount of energy in the shortest time Gallium-67 3.2 days to the malignant target cells, while sparing the Platinum-193m 4.3 days healthy ones from unwanted radiation. The dep- Ruthemum-97 2.9 days osition of energy is measured by what is known as Linear Energy Transfer (LET), which is dif- ferent for alpha, beta, or gamma radiation. Alpha emitters: Gamma radiation exhibits low values of Radionuclide Half-life Mean energy ( MeV) LET, as it penetrates relatively deeply, on the order of several centimeters, and does not dep- Bismuth-212 60.5 minutes 7.8 osit much energy along its track. Consequently, Astatine-21 1 7.2 hours 6.7 pure gamma-emitting radionuclides usually are Fermium-225 20.1 hours 7.0 not used for therapeutic purposes. Particle-emitting radionuclides, on the other hand, deposit greater energy near the site of localization, and hence are with iodine-131 for hyperthyroidism. Currently, Radionuclides for more suitable for therapeutic applications. a labelled compound known as iodine-131 medical therapy hi practice, radionuclides that emit beta par- MIBG is being used to treat a variety of tumours. ticles, as well as those capturing electrons and Among the "second generation" of beta- emitting what are known as Auger electrons, are emitting RPTs are samarium-153, rhenium-186, the only ones that have been used in therapeutic copper-67, and holmium-166. nuclear medicine. This is due to various reasons. Among alpha-particle emitters, only two Beta particles have penetration ranges in tissue radionuclides have been considered and studied on the order of millimeters to a few centimeters, as potential therapeutic agents: astatine-211 and appropriate depths for the irradiation of small- to bismuth-212. Largely because of the extremely medium-sized tumours. Secondly, some of the high radiotoxicity and short half-lives of alpha- most promising beta-emitting radionuclides emitting RPTs, a good deal of laboratory re- have desirable half-lives, varying from several search still is needed to develop them for medical hours to days. Lastly, many of these radio- therapy uses. nuclides are easily produced in nuclear research reactors, facilitating their availability. (See table.) Production of radionuclides Radionuclides emitting beta particles are widely used. They include phosphorus-32, stron- Independent of intended use, radionuclides tium-89, and iodine-131, which might be con- can be produced in nuclear research reactors and sidered the "first generation" of therapeutic in particle accelerators such as cyclotrons. Of the radionuclides. Their use in medicine dates back more than 300 nuclear research reactors in to the late 1930s. It is estimated, for example, operation throughout the world, more than 80 are that more than one million patients around the installed in developing countries. Cyclotrons world have been safely and effectively treated designed for radionuclide production are being IAEA BULLETIN, 1/1993 25 FEATURES Radiopharmaceuticals for cancer therapy Radionuclide Half-life Maximum energy (MeV) 89.3 hours 1.07 Rhemum-186 Over the past number of years, considerable 46.8 hours Samanum-153 0.80 interest has emerged in the use of radiophar- Holmium-166 26.4 hours 1.60 maceuticals to relieve intense bone pain result- Lutetium-177 6.7 days 0.50 ing from metastasis from breast, prostate, and Dysprosium-165 2.3 hours 1.34 lung cancer. Their application has been demon- Yttrium-90 64.8 hours 2.27 strated in clinical practice, and a number of Strontium-89 50.5 days 1.46 governmental and commercial laboratories are actively engaged in the development and clinical evaluation of RPTs for the treatment of patients Radionuclides installed in increasing numbers in both indus- with painful skeletal metastasis. produced in trialized and developing countries. It is esti- The prevalence of metastatic bone cancer in research reactors mated that some 150 cyclotrons totally or partial- nearly all countries creates a large need for the for potential bone ly dedicated to radionuclide production will be in development of new palliative agents. It is es- cancer therapy operation in the next few years. timated that about half of all patients with car- Nuclear research reactors. As prolific sour- cinomas of the prostate, breast, and lung even- ces of low energy neutrons, nuclear reactors are tually develop skeletal metastasis. used to produce radionuclides via neutron ac- The disease causes intense pain and suffering tivation of appropriate target materials. for patients. The pain is frequently relieved by Depending upon the neutron flux of the the use of analgesics or even narcotics such as nuclear reactor, radionuclides produced by the morphine when the pain is intolerable. For ter- neutron activation method are in general of low minal patients, the use of bone-seeking RPT may to medium specific radioactivity.