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Nuclear medicine is defined as the use of radionuclides for diagnostic and therapeutic applications. The imaging modalities positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are based on γ-emissions of specific energies. The therapeutic technologies are based on β􏰀 -particle-, α-particle-, and Auger electron emitters. In oncology, PET and SPECT are used to detect cancer lesions, to determine dosimetry, and to monitor therapy effectiveness. In contrast, radiotherapy is designed to irreparably damage tumor cells in order to eradicate or control the disease‘s progression. Radiometals are being explored for the development of diagnostic and therapeutic radiopharmaceuticals. Strategies that combine both modalities (diagnostic and therapeutic), referred to as theranostics, are promising candidates for clinical applications. This review provides an overview of the basic concepts behind therapeutic and diagnostic radiopharmaceuticals and their significance in contemporary oncology. Select radiometals that significantly impact current and upcoming cancer treatment strategies are grouped as clinically suitable theranostics pairs. The most important physical and chemical properties are discussed. Standard production methods and current radionuclide availability are provided to indicate whether a cost-efficient use in a clinical routine is feasible. Recent preclinical and clinical developments and outline perspectives for the radiometals are highlighted in each section.

Targeted radiopharmaceuticals offer the possibility of improved imaging with reduced side effects. Up to now, a variety of biological receptors such as aptamers have been successfully radiolabeled and applied to diagnostic imaging of cancers. The concept of using radio-labeled aptamers for binding to their targets has stimulated an immense body of research in diagnostic nuclear medicine. These biological recognition elements are single-stranded oligonucleotides that interact with their target molecules with high affinity and specificity in unique three-dimensional structures. Because of their high affinity and specificity, the receptor-binding aptamers labeled with gamma emitters such as 99mTc, 64Cu, 111In, 18F and 67Ga can facilitate the visualization of receptor-expressing tissues noninvasively. Compared to the antibody-based radiopharmaceuticals, the radiolabeled aptamers provide a number of advantages for clinical diagnostics including high stability, low cost, and ease of production and modification, low immunogenicity and, especially, superior tissue penetration because of their smaller size. In this review, we present recent progresses and challenges in aptamer-based diagnostic radiopharmaceuticals and highlight some representative applications of aptamers in nuclear medicine.

Background Biological specimens from patients who have received radiopharmaceuticals are often collected for diagnostic testing and sent to clinical laboratories. Residual radiation has long been assumed to be minimal. However, literature is sparse and may not represent the specimen volumes or spectrum of radionuclides currently seen at National Cancer Institute (NCI)–designated cancer centers. This study examined the radiopharmaceuticals associated with patient specimens received in the hospital core laboratory and assessed the potential risk of external radiation exposure to laboratory personnel. Methods The types and amounts of radiopharmaceuticals administered in a large metropolitan hospital system were retrospectively examined over a 20-month study period. The associated biological specimens sent to the largest core laboratory in the system for testing were evaluated. In addition, manual survey meter assessment of random clinical specimens and weekly wipe tests were performed for 44 weeks, and wearable and environmental dosimeters were placed for 6 months. Results Over 11 000 specimens, collected within 5 physical half-lives of radiopharmaceutical administration, were processed by our laboratory. Manual survey meter assessment of random clinical specimens routinely identified radioactive specimens. If held in a closed palm for >2 min, many samples could potentially deliver a 0.02 mSv effective dose of radiation. Conclusions The laboratory regularly receives radioactive patient specimens without radioactive labels. Although the vast majority of these are blood specimens associated with low-dose diagnostic radiopharmaceuticals, some samples may be capable of delivering a significant amount of radiation. Recommendations for laboratories associated with NCI cancer centers are given.

Abstract:: The field of nuclear medicine is rapidly evolving due to the high demand of radiopharmaceuticals for diagnostic and therapeutic applications. The availability of a vast array of radioisotopes, improvement in radiolabeling strategies, and advancements in detection systems have also contributed to the progress in this field. Radiopharmaceuticals are mainly classified based on their application as diagnostic or therapeutic radiopharmaceuticals. These are available either as ready to use preparations or prepared at hospital radiopharmacy either using automated synthesis modules or by using freeze-dried cold kit formulations. Availability of freeze-dried cold kits for preparation of varied radiopharmaceuticals for targeting various organs and tissues played an essential role in the extensive use of 99mTc radiopharmaceuticals for diagnostic imaging by single-photon emission computed tomography (SPECT) imaging. Cold kits are especially suitable for the preparation of radiopharmaceuticals labeled with isotopes like 177Lu with relatively long half-life or radionuclides produced by radioisotope generators. A simplified procedure for the preparation of positron emission tomography (PET) radiopharmaceuticals is also desired to achieve images with higher resolution and sensitivity offered by PET. Robust kit formulations will simplify the preparation of PET radiopharmaceuticals and will contribute to extensive applications of positron emitters such as 68Ga. Several therapeutic radiopharmaceuticals are also being made using cold kits of the ligands. This review provides an update on diagnostic and therapeutic radiopharmaceuticals prepared using cold kits.

Radiopharmaceuticals are used in the diagnosis and management of various diseases. There are several reports of adverse reactions related to the use of radiopharmaceuticals, though it is not as common as conventional drugs. Adverse reactions related to radiopharmaceuticals have been not widely reported and documented. In this review, we have tried to summarize the adverse reactions associated with some of the commonly used radiopharmaceuticals.

The Code of Federal Regulations is a single-source repository of all rules and regulations promulgated by federal departments and agencies. In Title 10, Chapter 1, Part 35, Subpart D, §§35.100 to 35.290 detail regulations for the use of unsealed by product material not requiring a written directive (ie, diagnostic radiopharmaceuticals), and in Subpart E, §§35.300 to 35.396 detail regulations for the use of unsealed by product material requiring a written directive (ie, therapeutic radionuclides). Currently proposed changes for both Subparts D and E could have profound effects on patient care, public safety, and the practice of nuclear medicine, diagnostic radiology, and radiation oncology. This article details those proposed changes and actions under way to prevent promulgation of proposals that could negatively affect patient care and public safety.

Rhenium, the third-row congener of technetium, is often used to develop the macroscopic chemistry of potential 99mTc diagnostic radiopharmaceuticals. The rhenium analogues to 99mTc-furifosmin are being developed for potential radiotherapy of multidrug-resistant tumors. Complexes of the form trans-[MIII(PR3)2(N2O2-Schiff base)]+ are of interest for the potential imaging and treatment of multidrug-resistant tumors. Reaction of the tetradentate Schiff ligand 4,4′-[(1E,1′E)-[ethane-1,2-diylbis(azanylylidene)]bis(methanylylidene)]bis(2,2,5,5-tetramethyl-2,5-dihydrofuran-3-ol) (tmf2enH2) with the M(V) starting materials (nBu4N)[TcOCl4] and (nBu4N)[ReOCl4] gave the monomeric products trans-[TcOCl(tmf2en)] and trans-[ReOCl(tmf2en)], respectively. Reduction of in situ formed trans-[ReOCl(tmf2en)] by various tertiary phosphines yielded disubstitued Re(III) products of the general type trans-[ReIII(PR3)2(tmf2en)]+. The rhenium(III) compounds were found to be water-soluble and stable in aqueous solution. Reversible R...

This pharmacovigilance-based survey was aimed at determining the prevalence of, and association between, radiopharmaceuticals and adverse reactions to radiopharmaceuticals from 1975 to 2017 in Japan. The Subcommittee for Safety Issues of Radiopharmaceuticals of the Japan Radioisotope Association’s Medical Science and Pharmaceutical Committee mailed a form for reporting adverse reactions to radiopharmaceuticals to all institutes performing nuclear medicine examinations in Japan. This investigation included adverse reactions to diagnostic radiopharmaceuticals labeled with both single-photon- and positron-emitting radionuclides and therapeutic sodium iodide labeled with 131I. Each institute returned the reporting form to the subcommittee each time an adverse reaction occurred. Replies were obtained from 75% of the institutions. In total, 1099 adverse reactions were reported from 46,645,580 radiopharmaceutical administrations, giving a prevalence of 2.4 adverse reactions per 100,000 administrations (95% confidence interval 2.2–2.5). Adverse reactions were most frequently observed for 131I-iodomethylnorcholesterol (230.1/105 administrations), followed by 131I-HSA (76.3/105 administrations), 131I-sodium iodohippurate (31.2/105 administrations), and 99mTc-DTPA (12.0/105 administrations). Comparison of adverse reactions between before and after 1997 revealed that prevalence dropped from 3.7/105 administrations (95% confidence interval 3.5–4.1) to 1.5/105 administrations (95% confidence interval 1.4–1.6). During the study period, vasovagal reactions accounted for 50.3% of adverse reactions, fever for 7.5%, allergic reactions for 25.7%, and other for 16.5%; 3.7% of all adverse reactions were considered severe but none were lethal. A definite, probable, possible, less likely, and uncertain causal relationship with radiopharmaceuticals was observed in 13.1%, 33.7%, 39.9%, 6.2%, and 7.1% of adverse reactions, respectively. These results suggest that nuclear medicine staff must be aware of the possibility of adverse reactions from radiopharmaceuticals, despite their rarity.

Until recently, it has been challenging to engage Wall Street and large pharmaceutical companies in radiopharmaceutical opportunities. The modest economic prospects of most diagnostic radiopharmaceuticals have not attracted keen interest from the broader business community, despite the rapid advancement of diagnostic imaging capabilities and their increasingly crucial role in the therapeutic process. Similarly, compelling science supporting select radiopharmaceutical therapies in oncology has been overshadowed by the unique challenges posed by this class of drugs and historical commercial failures that serve as sobering reminders of risk. Fortunately, a few notable successes in the targeted radioligand therapeutic space are changing this dynamic, fueling a new flow of investor capital into these technologies and inciting increased merger and acquisition activity that has yielded significant value creation for investors. If the nuclear medicine industry is able to continue to effectively manage historical challenges, then there is significant opportunity for a new and promising wave of radioligand therapies to significantly change the oncology treatment paradigm and elevate the profile of the entire nuclear medicine sector.

New peptide-based diagnostic and therapeutic approaches hold promise for highly selective targeting of cancer leading to more precise and effective diagnostic and therapeutic modalities. An important feature of these approaches is to reach the tumor tissue while limiting or minimizing the dose to normal organs. In this context, efforts to design and engineer materials with optimal in vivo targeting and clearance properties are important. This Data In Brief article reports on biodistribution and radiation absorbed dose profile of a novel high affinity radiopeptide specific for bone marrow-derived tumor vasculature. Background information on the design, preparation, and in vivo characterization of this peptide-based targeted radiodiagnostic is described in the article “Synthesis and comparative evaluation of novel 64Cu-labeled high affinity cell-specific peptides for positron emission tomography of tumor vasculature” (Merrill et al., 2016) [1]. Here we report biodistribution measurements in mice and calculate the radiation absorbed doses to normal organs using a modified Medical Internal Radiation Dosimetry (MIRD) methodology that accounts for physical and geometric factors and cross-organ beta doses. Keywords: Molecular imaging, Tumor angiogenesis, Radiation absorbed dose, Diagnostic radiopharmaceuticals

The purpose of this article is to reconsider the manner in which the U.S. Food and Drug Administration (FDA) reviews diagnostic radiopharmaceuticals. Mass characteristics of several common nonradioactive drugs and several diagnostic radiopharmaceuticals are considered. A history of the regulation of radiopharmaceuticals is presented. The Society of Nuclear Medicine and Molecular Imaging and the American College of Nuclear Medicine should choose the membership of a radiopharmaceutical advisory committee, and the FDA should contract with them to do so. Members of the radiopharmaceutical advisory committee should decide on the data to be presented by the manufacturer or the compounder and review those data, and the FDA should honor their decision. In this way, requirements would be radiopharmaceutical-specific, and much information of questionable usefulness would be foregone.

This study sought to answer the calls that have been made for the European Association of Nuclear Medicine to restore its surveys of reported adverse reactions. We assessed all reports of adverse reactions to radiopharmaceuticals that were submitted to the British Nuclear Medicine Society (BNMS) online database (Radiopharmaceutical Adverse Events and Product Defects) from January 2007 to December 2016. Methods: This investigation was a pharmacovigilance-based, nonexperimental, cross-sectional study aimed at finding the prevalence of, and association between, radiopharmaceuticals and adverse reactions. Results: During the study period, there were 204 reports of radiopharmaceutical adverse reactions, of which 13 were considered invalid, primarily because of incomplete entries or because a causal relationship between the radiopharmaceutical and the adverse reaction could not be determined. Tetrofosmin (34 reports) and oxidronate (32 reports) had the highest prevalence, followed by medronate (21 reports) and then sestamibi and nanocolloid (14 reports each). Rash (84 reports), itching (46 reports), and vomiting (30 reports) were the 3 most frequently occurring adverse reactions. Most reports (96.8%) were for diagnostic radiopharmaceuticals. Conclusion: The prevalence of adverse reactions to radiopharmaceuticals reported in the BNMS database remains low, with a frequency of 3.1 reports per 100,000 administrations in 2013 and 2.5 per 100,000 administrations in 2015. In our review spanning 10 years, we did not find any particular concern about the use of radiopharmaceuticals.

See the associated article on page [868][1]. This article provides readers with some background on concerns raised by Dr. Marcus about the evaluation of radiopharmaceuticals in this issue of The Journal of Nuclear Medicine ([1][2]). In 1975, the U.S. Food and Drug Administration (FDA) removed the

The EU regulation 536/2014 aims to facilitate the experimental use of diagnostic radiopharmaceuticals in particular for GMP requirements and needs to be applied in EU countries. As definitely clarified by this survey, the application is still far from being completed due to national restrictions that are conflicting with the content of the above EU regulation. Although the nuclear medicine centers are obliged to be compliant with national regulatory, national authorities have to be required to work towards full application of the regulation. On the other hand, an update of 536/2014 that includes therapeutic radiopharmaceuticals would also be beneficial to a rational and safe advance of nuclear medicine.

The literature on metal complexes with ethylenediaminedicarboxylic acids and their derivatives as promising pharmacological and diagnostic agents was reviewed. Complexes of platinum-group metals are promising anticancer agents. Bactericidal and fungicidal properties were found for several Pt(IV) and Pd(II) complexes. Complexes of Zn(II) and VO(IV) with ethylenediamine-N,N'-dicarboxylic acids were viewed as hypoglycemic (insulin-mimetic) agents. Complexes of radionuclides (99mTc, 111In, 67Ga) were described as diagnostic radiopharmaceuticals.

This chapter presents information on the clinical uses of diagnostic radiopharmaceuticals in nuclear medicine. The presentation is based on individual organs and common diseases. For each organ, a brief description of anatomy, different radiopharmaceuticals, and techniques employed for imaging is included. For tumors and tissue-specific diseases, the pathophysiology of the disease, radiopharmaceuticals, and imaging techniques used for their detection are given. PET/CT and SPECT/CT are commonly used for imaging and their pros and cons discussed. The mechanism of radiotracer uptake in the organ and tissues is elucidated. Wherever appropriate, relevant data are presented in tables. Appropriate illustrations of images depicting normal and/or disease states in humans are provided in support of the contents in the text. Pertinent questions and references related to the chapter are added at the end.

The safety and efficacy expectations for U.S. Food and Drug Administration (FDA) approval of diagnostic radiopharmaceuticals (DRs) are described in laws that broadly apply to all prescription drugs and biologic products. These laws also outline efficacy expectations that are unique for DRs. The FDA regulations and guidance documents elaborate on DR efficacy expectations for clinical uses of the drugs, such as the delineation of anatomy, the characterization of a physiologic process, or the diagnosis of disease. As described in the FDA regulations, the approval of a DR necessitates that the imaging drug has the ability to provide clinically useful information. Here we cite approved DRs to illustrate how the imaging performance of the drugs was characterized in clinical studies and the clinical usefulness of the imaging information described in drug labels.

This paper presents a systematic analysis of the inherent uncertainty in internal dose calculations for radiopharmaceuticals. A generic equation for internal dose is presented, and the uncertainty in each of the individual terms is analyzed, with the relative uncertainty of all terms compared. The combined uncertainties in most radiopharmaceutical dose estimates will be typically at least a factor of 2 and may be considerably greater. In therapy applications, if patient-individualized absorbed doses are calculated, with attention being paid to accurate data gathering and analysis and measurement of individual organ volumes, many of the model-based uncertainties can be removed, and the total uncertainty in an individual dose estimate can be reduced to a value of perhaps +/-10%-20%. Radiation dose estimates for different diagnostic radiopharmaceuticals should be appreciated and considered, but small differences in dose estimates between radiopharmaceuticals should not be given too much importance when one is choosing radiopharmaceuticals for general clinical use. Diagnostic accuracy, ease of use, image quality, patient comfort, and other similar factors should predominate in the evaluation, with radiation dose being another issue considered while balancing risks and benefits appropriately.

Originally, nuclear medicine focused on radiopharmaceuticals trapped in organ structures, based on their function, and the presence of disease was seen by the absence of radioactivity. More recently, target-specific radiopharmaceuticals have been developed to visualize and/or treat oncological diseases. Since radiopharmaceuticals have historically a leading position in the search for “molecular imaging”, it would be a waste not to learn from the pitfalls and opportunities that have been and are found during the development of radiopharmaceuticals. This knowledge can be used in the improvement of contrast agents for other imaging modalities like MRI and CT. In this article the aspects that are needed for the use of current and future therapeutic and diagnostic radiopharmaceuticals are described. Especially the production and development of therapeutic and imageable radiopharmaceuticals are demonstrated. MRI or CT can sometimes also image stable isotopes of elements that contain useful radionuclides. This can result in real multimodality imaging. Combining imaging modalities and imaging agents will result in better patient care and can only be advantageous if all departments and institutes will collaborate on their research work. The combination of approaches together with the fast progress in developments in the medical imaging world will result in a bright future for imaging driven therapy of cancer.

Background: Radiopharmaceuticals are regarded as safe by the nuclear medicine community, but up to now, no survey has been conducted with from the perspective of pharmacovigilance. Objective: To describe the adverse reactions to radiopharmaceuticals (ARRPs) reported to the French Pharmacovigilance Database (FPVD). Methods: We selected and described all reports encompassing at least one radiopharmaceutical in the FPVD. The annual incidence of reported ARRPs used in diagnosis was also estimated. Results: From 1989 to 2013, 304 reports of ARRPs were identified (43.0% serious, 12 deaths) in 54.6% women and 45.4% men; the median age was 58 years. Five therapeutic radiopharmaceuticals (131I-sodium iodide, 131I-lipiodol, 89Sr-chloride, 153Sm-lexidronam, and 90Y-ibritumomab-tiuxetan) were involved in 48 reports (97 adverse reactions: 86.6% serious, 9 deaths). Pulmonary disorders represented 44.3% of ARRPs used for therapy, mainly related to 131I-lipiodol. There were 34 diagnostic radiopharmaceuticals involved in 256 reports (451 adverse reactions: 38.1% serious, 3 deaths); 8 diagnostic products (99mTc-oxidronate, 18F-fluorodeoxyglucose, 99mTc-tin pyrophosphate, 99mTc-tetrofosmin, 99mTc-dimercaptosuccinic acid, 201Tl-chloride, 99mTc-sestamibi, and 111In-pentetate) accounted for two-thirds of ARRPs. The most frequent adverse reactions were skin (34.4%), general (18.2%), nervous (9.0%), and gastrointestinal disorders (7.0%). There were 25 cases of altered images and 10 medication errors. The annual incidence of reported adverse reactions ranged from 1.2 × 10−5 to 3.4 × 10−5 diagnostic administrations. Conclusions: Reported ARRPs occurred rarely and were more serious in the therapeutic than in the diagnostic field. The notification of ARRPs was able to provide new guidance for safe use, as was the case for 131I-lipiodol. Therefore, it is important to report ARRPs to a pharmacovigilance system.

Background Errors in medicine are being increasingly highlighted. There is potential for harm in nuclear medicine. Aim To evaluate the frequency, type, causes and adverse effects of nuclear medicine radiopharmaceutical maladministrations reported to the New South Wales Environment Protection Authority. Methods We reviewed reports received by the New South Wales Environment Protection Authority over a 5-year period. The number and type of maladministrations, contributing factors and any adverse effects were recorded. Comparison was made with the total number of medicare-paid diagnostic and therapeutic nuclear medicine services undertaken in New South Wales for the same period. Results Fifty-seven maladministrations were reported to the New South Wales Environment Protection Authority. There were 666179 nuclear medicine procedures recorded in New South Wales for the same period. Of the 57 reported maladministrations, the majority (n=34; 61%) were a result of incorrect radiopharmaceutical dispensing. Incorrect reading of labels attached to the syringe (n=8; 14%) and incorrect patient identification (n=7; 12%) accounted for most of the rest of the accidents. Most (n=48; 84%) involved 9 9 m Tc-based radiopharmaceuticals for diagnostic use, with three cases involving 1 3 1 I for therapeutic use. In 96% of cases - those which involved diagnostic radiopharmaceuticals - there were no immediate adverse clinical outcomes. However, one subject developed unintended hypothyroidism as a result of the maladministration of 1 3 1 I for therapy. Conclusion Nuclear medicine maladministrations in New South Wales are uncommon, with approximately 8-9 incidents per 100000 procedures. Most maladministrations are the consequence of incorrect radiopharmaceutical dispensing. All those which involved diagnostic radiopharmaceuticals resulted in no immediate adverse effects from the radiation exposure.

In the article on drugs in breastfeeding,1 I was dismayed at the inclusion of ‘radiopharmaceuticals’ in the table of drugs contraindicated in breastfeeding. There was little elaboration within the article as to the reason for this. The other drugs listed have sufficient evidence of the potential for serious adverse effects to the infant. This evidence simply does not exist for diagnostic radiopharmaceuticals.

Diagnostic radiopharmaceuticals should reflect in vivo biochemistry. Therapeutic radiopharmaceuticals should kill tumor cells while sparing healthy cells. As the understanding of a biological process increases, synthetic chemists must be ever poised to improve the design of new radiotracers to reflect the in vivo scenario in an accurate and precise fashion. However, it is somewhat ironic that, due to genetic variability, there is an inverse relationship between the specificity of the radiotracer and the number of individuals who will eventually be helped by these discoveries. Regardless of the beauty of the science that underpins radiopharmaceutical development, the availability of financial resources will direct the overall progress in the field.

The progress in diagnostic nuclear medicine over the years since the discovery of 99m Tc is indeed phenomenal. Over 80% of the radiopharmaceuticals currently being used make use of this short-lived, metastable radionuclide, which has reigned as the workhorse of diagnostic nuclear medicine. The preeminence of 99m Tc is attributable to its optimal nuclear properties of a short half-life and a gamma photon emission of 140 keV, which is suitable for high-efficiency detection and which results in low radiation exposure to the patient. 99m TcO 4 − , which is readily available as a column eluate from a 99 Mo/ 99m Tc generator, is reduced in the presence of chelating agents. The versatile chemistry of technetium emerging from the 8 possible oxidation states, along with a proper understanding of the structure-biologic activity relationship, has been exploited to yield a plethora of products meant for morphologic and functional imaging of different organs. This article reviews the evolution of 99m Tc dating back to its discovery, the development of 99 Mo/ 99m Tc generators, and the efforts to exploit the diverse chemistry of the element to explore a spectrum of compounds for diagnostic imaging, planar, and single photon emission computed tomography. A brief outline of the 99m Tc radiopharmaceuticals currently being used has been categorically presented according to the organs being imaged. Newer methods of labeling involving bifunctional chelating agents (which encompass the "3+1" ligand system, Tc(CO) 3 +1 -containing chelates, hydrazinonicotinamide, water-soluble phosphines, and other Tc-carrying moieties) have added a new dimension for the preparation of novel technetium compounds. These developments in technetium chemistry have opened new avenues in the field of diagnostic imaging. These include fundamental aspects in the design and development of target-specific agents, including antibodies, peptides, steroids, and other small molecules that have specific receptor affinity.

This work aims to complete the dosimetric information available in the report No. 19-2001 of the French Society of Medical Physics (FSMP). This work is designed to help nuclear medicine professionals in the assessment of patient dose during diagnostic examinations in nuclear medicine. It takes into account a number of recent developments in France, such as the emergence of PET scanners and hybrid SPECT/CT cameras in nuclear medicine departments. In order to remain consistent with the FSMP report No. 19-2001, the effective dose was calculated according to the methodology applied in ICRP publication 60 (1991). A new reference system for performing dosimetric calculations has been introduced in ICRP publication 103 (2007) but the data necessary for nuclear medicine applications are not yet validated on a large scale. Therefore, this work focused on updating dosimetric data from the latest ICRP publications (106, 128) or from the literature, especially in the case of PET tracers. The radiation dose assessments for the neonate and fetus were updated for fluorine-18. Breastfeeding recommendations were revised: the working group adopted a new method to estimate the exposure of newborn by internal contamination in breast milk and by external radiation during periods of contact. The working group also collected the administered doses in common nuclear medicine examinations from guidelines of several learned societies (SFMN, EANM) and from French regulations (diagnostic reference levels, marketing authorization). Through this document, the working group wished to encourage nuclear medicine professionals to follow existing recommendations on administered doses, especially in pediatric and PET examinations. Finally, CT radiation dose from hybrid imaging systems was addressed by giving some examples of dose assessment in the limited context of anatomical localization and attenuation correction.

For almost 100 years, radioactivity has been one of the major tools in medicine. Therapeutic applications that began with 226Ra and 222Rn implants have rapidly grown to include about 20 radionuclides with radiations specifically chosen to treat at different depths in tissue — ranging from a few millimeters for intravascular therapy to a few centimeters in the case of large solid tumors. Systemic treatments with radiopharmaceuticals have grown from the traditional 131I to more than ten candidate nuclides which are to be labeled to tumor-specific radiopharmaceuticals. Diagnostic radiopharmaceuticals are used in over 13 million procedures in the United States annually. About 40 nuclides are under investigation for these applications including single photon emitters for SPECT (single photon emission computed tomography) and positron emitters for PET (positron emission tomography). In addition to the mainstays of therapeutic and diagnostic radiology, radionuclides are widely used for in vitro tracers in the life sciences and represent one of the main tools in the field of molecular biology.

One of the radiopharmaceuticals that were used for diagnostic is conducted by using Technetium-99m (99mTc), which could be obtained from Molybdenum-99 (99Mo) separation. This research was conducted to determine the adsorbent polymer variation effect at two zirconium chromatography systems to obtain 99mTc yield more than 80%. Polymers were used zirconium-TEOS as adsorbents in the first system while the second system used Zirconium-TEOS-methanol. The same method was conducted for both systems. The preparation was done by adding 99Mo on both polymers and heated at 90 °C temperature for three hours. Elution process of 99Mo and 99mTc was conducted by using column chromatographic system, in which the column filled with Alumina is connected to the Zirconium polymer column. The elution process was conducted on the next day until 10th fractions. Both of the systems showed the 99mTc radionuclides were highest eluted at the 3rd fraction then they decline to constant at the 10th fraction. The 99mTc yield in the system 1 was 58% and the system 2 was 96.23%. The elution from the system 1 was not analyzed by Atomic Absorption Spectrometer (AAS) because the 99mTc yield was less than 80%. Analysis results using AAS on the system 2 found out that the system 2 contained Si 1.11 ppm, and no other elements (Mo and Zr) was obtained. Based on Lethal Dose 50 (LD50), it is showed that the elution of system 2 is below the threshold (Mo = 4000 mg /kg, Zr = 489 mg /kg and Si = 22.5mg /kg), therefore it was safe to be used for diagnostic radiopharmaceuticals.

A real-time automatic dose dispenser (RADD) has been designed and fabricated for automatic withdrawal and calibration of diagnostic radiopharmaceuticals such as those labelled with (99m)Tc. This system enhances the accuracy and precision of activity measurements and reduces personal radiation exposure. The structure, function, user-friendliness and performance of this device are described and examined for diagnostic activities of (99m)Tc ranging from 50 to 650 MBq. The results show that the RADD minimises the likelihood of miscalibration of radiopharmaceuticals due to human error and results in significantly reduced variability (i.e. higher precision) in dispensed activities of radiopharmaceuticals.

Purpose The impact on patients’ health of radiopharmaceuticals in nuclear medicine diagnostics has not until now been evaluated systematically in a European context. Therefore, as part of the EU-funded Project PEDDOSE.NET (www.peddose.net), we review and summarize the current knowledge on biokinetics and dosimetry of commonly used diagnostic radiopharmaceuticals. Methods A detailed literature search on published biokinetic and dosimetric data was performed mostly via PubMed (www.ncbi.nlm.nih.gov/pubmed). In principle the criteria for inclusion of data followed the EANM Dosimetry Committee guidance document on good clinical reporting. Results Data on dosimetry and biokinetics can be difficult to find, are scattered in various journals and, especially in paediatric nuclear medicine, are very scarce. The data collection and calculation methods vary with respect to the time-points, bladder voiding, dose assessment after the last data point and the way the effective dose was calculated. In many studies the number of subjects included for obtaining biokinetic and dosimetry data was fewer than ten, and some of the biokinetic data were acquired more than 20 years ago. Conclusion It would be of interest to generate new data on biokinetics and dosimetry in diagnostic nuclear medicine using state-of-the-art equipment and more uniform dosimetry protocols. For easier public access to dosimetry data for diagnostic radiopharmaceuticals, a database containing these data should be created and maintained. Electronic supplementary material The online version of this article (doi:10.1007/s00259-011-1904-z) contains supplementary material, which is available to authorized users.

Molecular imaging combines non-invasive imaging methods with tools of molecular and cellular biology. Traditional imaging approaches in nuclear medicine were solely based on the detection of anatomical and structural features. Complementary to these conventional methods, advances in biology made it possible to visualize cellular and biochemical processes. Until the event of PET imaging, the spectrum of nuclides used for tracers was largely restricted to iodine isotopes and 99 m-technetium. Today, several PET nuclides have largely extended the possibilities of tracer design. The uptake of several archetypical diagnostic radiopharmaceuticals is illustrated in Figs. 18.1–18.3. Yet most of the commonly used tracers are derivatives of natural products. At present, the main effort in the field of radiotracer development is the identification of specific probes for targeting cellular structures, e g. tumour-associated receptors. These new ligands can be used for diagnosis as well as for treatment, a concept known as theranostics. Further, non-invasive imaging paradigms studied in small animals are currently being translated into the clinics. In the future, molecular imaging will provide new ways in the diagnosis of cancer and monitoring treatment response in oncology. For instance, studies using PET-based imaging of reporter genes have already been described in gene therapy approaches.

The annual per caput effective dose and the genetically significant dose to the Australian population, arising from the practice of nuclear medicine, were estimated from the results of a survey of all major hospitals. The survey was conducted for a 4-wk time period during June-July 1991. Patients were characterized by age and gender. The use of diagnostic radiopharmaceuticals resulted in values of 64 microSv and 26 microSv per caput for effective dose and the genetically significant dose, respectively. The effective dose has shown a marked increase in the last decade. These values may be compared to the estimated 2 mSv from natural background radiation.

Selective, tailored chelators are of importance in medicine for the treatment of metal intoxication, or to stabilise metal cations in diagnostic radiopharmaceuticals and paramagnetic contrast agents. In this report, the co-ordination chemistry of polyamines, polyalcohols, and polyamino-polyalcohols is examined and some general prerequisites for a successful design of tailored chelators are summarised. The metal binding properties of 1,3,5-triamino-1,3,5-trideoxy-cis-inositol (taci), a rigid, cyclohexane-based polyamino-polyalcohol, are reviewed. Concepts for the design of selective chelators which are based on the taci structure are presented, and the potential of such ligands for medical applications is briefly discussed.

The twenty years old cyclotron U‐120M was upgraded for R&D and Production of Radiopharmaceuticals. R&D on short‐lived Radiopharmaceuticals production is done at this accelerator. These Radiopharmaceuticals are eventually delivered to nearby hospitals. Development of new diagnostic radiopharmaceuticals is also pursued at the facility. your paper.

A drug administered to humans is likely to elicit some adverse reactions, so radiopharmaceuticals, when administered in vivo, also are expected to have some adverse reactions. Diagnostic radiopharmaceuticals are normally less toxic than therapeutic agents. In this chapter, the adverse reactions induced in humans by common radiopharmaceuticals are presented in a table. Also in vivo biodistribution of radiopharmaceuticals may be altered by interaction with the drugs or chemicals which the patient is taking. These drug interactions are shown in a table.