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Vol. 33 No. 1
January-February 2011
 
Medicine after the Discovery of Radium

by Julian Liniecki

In the final decade of the 19th century, several important findings in the domain of physics had a major influence upon the field of medicine. The first was the discovery by Wilhelm Conrad Röntgen of X-rays and their basic characteristics (Eisenberg, 1992; Hellman, 1996). The second was made by Marie Skłodowska-Curie and her husband Pierre Curie, who proved that radiation emitted by uranium ore originates in the ore itself and comes from a new element they named radium. The Curies developed a technique for isolating radium, but they refrained from patenting the process in the belief that the potential benefits to society from the new element—especially in medicine—were too great to keep to themselves.

As predicted, it wasn’t long before radium and X-rays found widespread application in medicine. However, in the early years the low electric potential between poles of the cathode bulb and low current intensity made it difficult to use X-rays for diagnostic imaging. Over the next 20 years, these disadvantages had been gradually, but effectively eliminated so that during World War I,
X-ray machines were put to widespread use in medical units and hospitals, both permanently installed and mounted on ambulance cars to diagnose wounded soldiers. In fact, Marie Curie pushed for the use of these mobile radiography units, which came to be known as petites Curies. In 1914, Marie and her 17-year-old daughter Irène took their first trip to the battlefront in one of these ambulances.

Early proponents of the
medical use of radium argued for its widespread, almost
indiscriminate application.

Around this time, the first attempts were made to use X-rays for the treatment of superficial skin ailments (Eisenberg 1992). In the early 20th century the treatment of pathological foci localized in deeper spaces of human body was still ineffective because of the low energy of X-ray quanta and their poor penetrating power. It was not until the 1920s and 1930s that X-ray machines were developed that utilized higher voltage (called orthovoltage) in the range of 120–140 kV. From this point forward, the new specialty of radiology rapidly emerged.

There was a great deal of early interest in using radium in medicine, although some proponents argued for widespread, almost indiscriminate application. Quite soon it became obvious that when introduced into the human body in the form of a solution it was quite harmful or even deadly. Thankfully, dangers of this practice were promptly recognized and these treatments discontinued.

The use of radium for cancer treatment was soon recognized as an effective therapy. The therapy involved the use of sealed metal containers containing radium salts that were placed inside the patient’s body close to the tumor site. Cancer of the uterine cervix was treated with radium tubes more than other malignancy. This procedure was commonly used up through the 1960s and 1970s until other radionuclides were substituted.

A number of other types of malignant tumors have been treated with radium as well. Radium tubes were used to treat skin cancer and mammary carcinoma. This type of treatment, called brachytherapy, allowed for the irradiation of many patients per day by the same installation. It is still used today, with dose distribution between the tumor and healthy tissues close to optimal.

Radium was also used inside needles that were inserted into the mouth, lip, and other areas. Later, surgeons were able to plant tiny doses of radium close to the tumor bed, minimizing exposure to the radiation. Effectiveness of this procedure contributed to the emergence of oncological radiotherapy (Del Regato 1993).

Following the discovery of radium’s medical potential, numerous Radium Institutes were established in several countries (e.g., Paris, Stockholm, and Warsaw). Marie Curie’s role in this activity cannot be overestimated.

An important milestone in radiation treatment occurred when Rolf Sievert’s definition of the dose of radiation (exposure) was accepted by the II International Congress of Radiology in Stockholm in 1928. Since then, steady improvements in dosimetry have taken place. By substituting other gamma ray emitting radionuclides of very high activity, obtained later from fission products and/or nuclear reactions, doctors radically shortened the time of local irradiation.

For effective radiological treatment with gamma rays (e.g., from 60Co and other sources) and with ionizing beta particles and quanta from accelerators, an accurate dosimetry is essential. Optimal irradiation of a tumor means achieving the highest planned dose in the tumor volume (called target) while reducing the dose—as effectively as possible—in neighboring healthy tissues. The modern tools for satisfying such demands include precise three-dimensional imaging of tumors and healthy tissues using X-ray tomography and magnetic resonance imaging. Sophisticated computer programs are used to steer the irradiation procedure. In recent decades, three-dimensional irradiation has become more commonplace. It involves the dynamic adaptation of radiation-beam crossections (beam shape and intensity modulation) to concentrate the dose at the target tumor while reducing the impact on healthy tissues that the beam travels through.

Another more recent advance has been the use of proton-beam therapy to treat a variety of tumor types. With proton-beam irradiation, the distribution of doses is very close to theoretically optimal and the treatment appears to be more effective than traditional radiation therapy. However, it requires a very high investment which has limited its availability to a few oncological centers.

The practical problem encountered early in the history of radiotherapy was how to irradiate patients and their tumors. It became quite clear that application of a single high dose (X, gamma rays) of radiation to the tumor led to serious damage of neighboring healthy tissues and life-endangering complications. After numerous studies (experimental, clinical, and epidemiological) it became clear that the fractionation of radiation doses was the solution.

The discovery of artificial radioactivity by Frédéric and Irène Joliot-Curie in 1934 as well as the controlled fission of uranium 235 atoms in nuclear reactors lead to the availability of a large number of radioactive nuclides for use in medicine. By binding selected nuclides with molecules that have affinity to various tissues and organs, researchers created a category of compounds called radiopharmaceuticals, which are now widely used for diagnostic and therapeutic purposes.

As scientists developed instrumentation to detect and follow radiopharmaceuticals in the human body, a new branch of science emerged: nuclear medicine. One of the milestones in this field was the development of positron emission tomography (PET), a three-dimensional imaging technique which allows physicians to follow specific processes in the body. A so-called tracer, a positron-emitting radionuclide, is introduced into the body on a biologically active molecule, and the annihilation events are detected and followed in space and time.

The most commonly used tracer is a derivative of glucose (18F-fluorodeoxyglucose), which is readily taken up by cancerous cells. This enables detection and localization of cancerous cells and tissues. In addition, PET scans are used to understand the metabolic activity of tissues and can therefore be used to study and diagnose a range of physiological and pathological processes.

In recent decades, targeted radionuclide therapy has shown promise as an effective form of treatment for certain cancers with far fewer side effects than traditional radiation therapy. Several procedures of this type have been developed and validated for several tumor types (e.g., malignant lymphoma). The concept depends on use of molecules labeled with radionuclide to deliver radiation to cancerous cells in disease sites. Radiation may come from nuclides emitting alpha- and beta- particles or Auger electrons. The affinity of molecules to cancer cells results from genetic characteristics (immunotherapy). Two drugs in particular, 90Y-ibritumomab tiuxetan-“Zevalin” and 131Itositumomab (Bexxar) used for the successful treatment of indolent B-cell lymphoma, have confirmed that the concept of targeted radionuclide therapy has great potential (NRC 2007).

A century ago, few could have foreseen that the discoveries of Wilhelm Röntgen and Marie Skłodowska-Curie would lead to radiotherapy becoming one of the mainstays of treatment for cancer. According to available statistics, there were approximately 5 million patients treated with ionizing radiation annually between 1991 and 1996 (UN 2000). Regretfully, because the treatment is often expensive and highly complicated and there is limited availability of medical staff and appropriate technology, the therapy is unavailable to a large proportion of the world’s population.

Dr. Med. Julian Liniecki is professor emeritus of nuclear medicine at the Medical University of Lodz, Poland; he was a member of the International Commission on Radiological Protection from 1969 to 2008.

See the References section for works cited in this article.


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