Radioactive Artifacts: Historical Sources of Modern Radium Contamination.

Radium has been distributed in a wide variety of devices during the early part of this century. Antique objects containing significant amounts of radium turn up at flea markets, antique shows, and antique dealers, in a variety of locations. These objects include radium in devices which were used by legitimate medical practitioners for legitimate medical purposes such as therapy, as well as a wide variety of "quack cures." These devices may contain anywhere from a few nanocuries to as much as several hundred microcuries of radium. In addition to medical sources, a large variety of scientific instruments utilize radium in luminous dials. These instruments include compasses, azimuth indicators, and virtually any object which might require some form of calibration. In addition, the consumer market utilized a large amount of radium in the production of wrist watches, pocket watches, and clocks with luminous dials. Some of these watches contained as much as 4.5 µCi of radium, and between 1913 and 1920 about 70 gm was produced for the manufacture of luminous compounds. In addition to the large amount of radium produced for scientific and consumer utilization, there were a number of materials produced which were claimed to contain radium but in fact did not, further adding to the confusion in this area. The wide availability of radium is a result of the public's great fascination with radioactivity during the early part of this century and a belief in its curative properties. A number of objects were produced in order to trap the emanations of radium in water for persons to drink in order to benefit from their healing effects. Since the late 20s and early 30s the public's attitude towards radiation has shifted 180° and it is now considered an extremely dangerous and harmful material. However, even as late as the 1950s, there were still some items produced containing radioactivity which today would be unthinkable. The "Buck Rogers Mystery Ring" of the 1950s was activated with polonium. With the shift in public attitudes towards radioactivity, and increasing problems in disposal of radioactive materials, the disposal of radium presents a particularly perplexing problem. The radium which was produced in the early part of the century is still around in various forms and is extremely difficult to dispose of. All objects discovered claiming to contain radium should be taken seriously and should be properly surveyed. They then should either be stored in some area where the environment is protected from the radioactivity or if a very small amount of radium is present, they may be disposed of through one of several commercial sources. Any significant amount of radium is extraordinarily difficult and expensive to dispose of and there are only limited sites which will accept these materials. No clear cut, uniform mechanism for the handling of radioactive materials which turn up outside of the usual institutional sources, is currently in place.

Classics in Neuroimaging: Imaging the Dopaminergic Pathway with PET.

The success of positron emission tomography (PET) for observing molecular processes underlying brain function and disease is underpinned by radiotracer chemistry. From the earliest applications of PET to measure dopamine synthesis capacity and the abundance of neuroreceptors and transporters, to the more recent topic of dynamic neurochemical imaging, interrogation of brain dopamine in conditions such as neurodegenerative diseases, schizophrenia, mood disorders, and addictions has been a driving force that challenges the ingenuity of radiopharmaceutical scientists. In fact, the pursuit of new ligands and reaction methods to address longstanding challenges has often been pioneered in the context of dopamine imaging. From this viewpoint, we highlight the unique history of imaging the dopaminergic pathway with PET, and present our interpretation of how this worldwide effort shaped and continues to drive the field of molecular imaging.

Discovery of rhenium and masurium (technetium) by Ida Noddack-Tacke and Walter Noddack. Forgotten heroes of nuclear medicine.

The history of the early identification of elements and their designation to the Mendeleev Table of the Elements was an important chapter in German science in which Ida (1896-1978) and Walter (1893-1960) Noddack played an important role in the first identification of rhenium (element 75, 1925) and technetium (element 43, 1933). In 1934 Ida Noddack was also the first to predict fission of uranium into smaller atoms. Although the Noddacks did not for some time later receive the recognition for the first identification of technetium-99m, their efforts have appropriately more recently been recognized. The discoveries of these early pioneers are even more astounding in light of the limited technologies and resources which were available during this period. The Noddack discoveries of elements 43 and 75 are related to the subsequent use of rhenium-188 (beta/gamma emitter) and technetium-99m (gamma emitter) in nuclear medicine. In particular, the theranostic relationship between these two generator-derived radioisotopes has been demonstrated and offers new opportunities in the current era of personalized medicine.

Nuclear medicine procedures in the diagnosis of NET: a historical perspective.

Novel diagnostic tools and therapies have emerged as a result of the continuous endeavors relating to neuroendocrine tumors (NETs). Nuclear medicine plays a pivotal role in the imaging and treatment of NETs. Somatostatin receptor analogues and metaiodobenzylguanidine remain front-line single-photon emission computed tomography (SPECT) radiotracers in the imaging of NET; their utility has been augmented by the increasing availability of SPECT/CT. Positron emission tomography has been growing rapidly in the imaging of NETs, paralleled by great efforts toward the development of new tracers. Hybrid imaging will play an important role in the future of NETs.

Historic images in nuclear medicine: 1976: the first issue of clinical nuclear medicine and the first human FDG study.

In 1976, 2 major molecular imaging events coincidentally took place: Clinical Nuclear Medicine was first published in June, and in August researchers at the Hospital of the University of Pennsylvania created the first images in humans with F-FDG. FDG was initially developed as part of an evolution set in motion by fundamental research studies with positron-emitting tracers in the 1950s by Michel Ter-Pegossian and coworkers at the Washington University. Today, Clinical Nuclear Medicine is a valued scientific contributor to the molecular imaging community, and FDG PET is considered the backbone of this evolving and exciting discipline.

Radiolabeled COX-2 inhibitors for non-invasive visualization of COX-2 expression and activity--a critical update.

Cyclooxygenase-2 (COX-2) is a key player in inflammation. Its overexpression is directly associated with various inflammatory diseases and, additionally, with several processes of carcinogenesis. The development of new selective COX-2 inhibitors (COXIBs) for use in cancer treatment is in the focus of the medicinal chemistry research field. For this purpose, a set of methods is available to determine COX-2 expression and activity in vitro and ex vivo but it is still a problem to functionally characterize COX-2 in vivo. This review focusses on imaging agents targeting COX-2 which have been developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT) since 2005. The literature reveals that different radiochemical methods are available to synthesize COXIBs radiolabeled with fluorine-18, carbon-11, and isotopes of radioiodine. Unfortunately, most of the compounds tested did not show sufficient stability in vivo due to de[¹8F]fluorination or de[¹¹C]methylation or they failed to bind specifically in the target region. So, suitable stability in vivo, matching lipophilicity for the target compartment and both high affinity and selectivity for COX-2 were identified as prominent criteria for radiotracer development. Up to now, it is not clear what approach and which model is the most suited to evaluate COX-2 targeting imaging agents in vivo. However, for proof of principle it has been shown that some radiolabeled compounds can bind specifically in COX-2 overexpressing tissue which gives hope for future work in this field.

A historical perspective on the specific activity of radiopharmaceuticals: what have we learned in the 35 years of the ISRC?

Specific activity (SA), defined as the amount of radioactivity per unit mass of a compound, is arguably one of the most important parameters in radiopharmaceutical development, particularly in quality control of carbon-11- and fluorine-18-labeled compounds. This review article will outline the progression of improvements in SA over the last few decades. The International Symposium of Radiopharmaceutical Chemistry abstracts were an excellent source of materials for this review and will be referenced throughout.

Rubin H. Flocks and colloidal gold treatments for prostate cancer.

In the early 1950s, Rubin H. Flocks of the University of Iowa began to treat prostate cancer patients with colloidal gold (Au(198)) therapy, evolving his technique over nearly 25 years in 1515 patients. We reviewed the long-term outcomes of Flocks' prostate cancer patients as compared to those patients treated by other methods at the University of Iowa before Flocks' chairmanship. We reviewed archived patient records, Flocks' published data, and long-term survival data from the Iowa Tumor Registry to determine short- and long-term outcomes of Flocks' work with colloidal gold. We also reviewed the literature of Flocks' time to compare his outcomes against those of his contemporaries. The use of colloidal gold, either as primary or adjunctive therapy, provided short- and long-term survival benefit for the majority of Flocks' patients as compared to historical treatment options (p < 0.001). Flocks' use of colloidal gold for the treatment of locally advanced prostate cancer offered short- and long-term survival benefits compared to other contemporary treatments.

The legal standards for the radioactive or non radioactive drugs research and approval in the European Community and in Germany after the thalidomide catastrophe.

The drug thalidomide was contained in the blockbuster Contergan, which has been used as a non- prescription sedative drug and a potent treatment for occurring morning sickness in pregnant women during the 1950s and the early 1960s. This therapeutic use has led to one of the most prominent disasters in the history of drug development due to peripheral neuritis and malformations, e.g. phocomelia, in babies whose mothers had taken thalidomide within their pregnancies. Moreover, this catastrophe initiated a change of paradigm in Germany as well as in Europe with regard to drug safety and the regulatory setting. This article describes the history of the use of thalidomide and the regulatory framework of drug approval at that time as well as changes after the Contergan disaster including considerations to radiopharmaceuticals. Additionally, aspects of drug safety in the different development phases of pharmaceuticals as well as radiopharmaceuticals, i.e. pre-clinical and clinical phases, are characterised. However, many drugs have been withdrawn from the market after approval due to changes with regard of their risk-benefit balance after the occurrence of adverse drug reactions. Thus, pharmacovigilance activities are also mentioned in this review article. Last, obstacles and future perspectives in the arena of drug research and development also considering the use of radiopharmaceuticals are delineated.