Lactate supports cell-autonomous ECM production to sustain metastatic behavior in prostate cancer.

Extracellular matrix (ECM) is a major component of the tumor environment, promoting the establishment of a pro-invasive behavior. Such environment is supported by both tumor- and stromal-derived metabolites, particularly lactate. In prostate cancer (PCa), cancer-associated fibroblasts (CAFs) are major contributors of secreted lactate, able to impact on metabolic and transcriptional regulation in cancer cells.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board.

Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development.

Main Body: This selection of highlights provides commentary on 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals.

Conclusion: Trends in radiochemistry and radiopharmacy are highlighted.

The DOTA macrocyclic cavity in metallic radiopharmaceuticals: Mythology or reality?

Background: The hypothetical concept of 'macrocyclic cavity' is largely employed as useful model to interpret the affinity of metal ions for the macrocyclic chelating ligand 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (HDOTA). It Is hypothesized that a close matching between the size of the macrocyclic cavity and that of the metallic ion is a key parameter to ensure the high-yield formation of stable coordination metal-DOTA complex. This approach has become popular in the design of radiopharmaceuticals containing radiometals and HDOTA as chelating group.

Fundamentals of Rhenium-188 Radiopharmaceutical Chemistry.

The β emitter, rhenium-188 (Re), has long been recognized as an attractive candidate for targeted cancer radionuclide therapy (TRNT). This transition metal shares chemical similarities with its congener element technetium, whose nuclear isomer technetium-99m (Tc) is the current workhorse of diagnostic nuclear medicine. The differences between these two elements have a significant impact on the radiolabelling methods and should always receive critical attention.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board.

Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development.

Main Body: This commentary of highlights has resulted in 21 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals.

Conclusion: Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field in various topics including new PET-labelling methods, FAPI-tracers and imaging, and radionuclide therapy being the scope of EJNMMI Radiopharmacy and Chemistry.

IAEA Contribution to Nanosized Targeted Radiopharmaceuticals for Drug Delivery.

The rapidly growing interest in the application of nanoscience in the future design of radiopharmaceuticals and the development of nanosized radiopharmaceuticals in the late 2000's, resulted in the creation of a Coordinated Research Project (CRP) by the International Atomic Energy Agency (IAEA) in 2014. This CRP entitled ' involved a team of expert scientist from various member states. This team of scientists worked on a number of cutting-edge areas of nanoscience with a focus on developing well-defined, highly effective and site-specific delivery systems of radiopharmaceuticals.

Synthesis and Characterization of Manganese Dithiocarbamate Complexes: New Evidence of Dioxygen Activation.

(1) Background: Metal dithiocarbamate compounds have long been the subject of research due to their ease of formation, excellent properties and potential applications. However, manganese complexes with dithiocarbamates, to our knowledge, have never been used for medical imaging applications. With the aim of developing a new class of mononuclear manganese(II)-based agents for molecular imaging applications, we performed a specific investigation into the synthesis of mononuclear bis-substituted Mn(II) complexes with dithiocarbamate ligands.

Highly Efficient Micro-Scale Liquid-Liquid In-Flow Extraction of Tc from Molybdenum.

The trend to achieve even more compact-sized systems is leading to the development of micro-scale reactors (lab-on-chip) in the field of radiochemical separation and radiopharmaceutical production. Technetium-99m extraction from both high and low specific activity molybdenum could be simply performed by MEK-driven solvent extraction if it were not for unpractical automation. The aim of this work is to develop a solvent extraction and separation process of technetium from molybdenum in a micro-scale in-flow chemistry regime with the aid of a capillary loop and a membrane-based separator, respectively.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board.

Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biyearly highlight commentary to update the readership on trends in the field of radiopharmaceutical development.

Results: This commentary of highlights has resulted in 23 different topics selected by each member of the Editorial Board addressing a variety of aspects ranging from novel radiochemistry to first in man application of novel radiopharmaceuticals.

Conclusion: Trends in radiochemistry and radiopharmacy are highlighted demonstrating the progress in the research field being the scope of EJNMMI Radiopharmacy and Chemistry.

IAEA contribution to the development of 64Cu radiopharmaceuticals for theranostic applications.

Copper-64 is a very attractive radioisotope with unique nuclear properties that allow using it as both a diagnostic and therapeutic agent, thus providing an almost ideal example of a theranostic radionuclide. A characteristic of Cu-64 stems from the intrinsic biological nature of copper ions that play a fundamental role in a large number of cellular processes. Cu-64 is a radionuclide that reflects the natural biochemical pathways of Cu-64 ions, therefore, can be exploited for the detection and therapy of certain malignancies and metabolic diseases.

The emerging value of 64Cu for molecular imaging and therapy.

Along with other novel metallic radionuclides, copper-64 (Cu) is currently being investigated as an alternative option to the gallium-68 (Ga) and lutetium-177 (Lu) radiopharmaceuticals widely used for targeting somatostatin receptors, expressed by neuroendocrine tumors (NETs), and recently prostate specific membrane antigen (PSMA), expressed by prostate cancer cells. This interest is mostly driven by the peculiar nuclear properties of Cu that make it an almost ideal example of theranostic radionuclide. In fact, Cu emits both low-energy positrons, β particles and a swarm of Auger electrons.

Review on Tc radiopharmaceuticals with emphasis on new advancements.

Rapid imaging acquisition, high spatial resolution and sensitivity, powered by advancements in solid-state detector technology, are significantly changing the perspective of single photon emission tomography (SPECT). In particular, this evolutionary step is fueling a rediscovery of technetium-99m, a still unique radionuclide within the nuclear medicine scenario because of its ideal nuclear properties and easy preparation of its radiopharmaceuticals that does not require a costly infrastructure and complex procedures. Scope of this review is to show that the arsenal of technetium-99m radiopharmaceuticals is already equipped with imaging agents that may complement and integrate the role played by analogous tracers developed for positron emission tomography (PET).

LARAMED: A Laboratory for Radioisotopes of Medical Interest.

The widespread availability of novel radioactive isotopes showing nuclear characteristics suitable for diagnostic and therapeutic applications in nuclear medicine (NM) has experienced a great development in the last years, particularly as a result of key advancements of cyclotron-based radioisotope production technologies. At Legnaro National Laboratories of the National Institute of Nuclear Physics (LNL-INFN), Italy, a 70-MeV high current cyclotron has been recently installed. This cyclotron will be dedicated not only to pursuing fundamental nuclear physics studies, but also to research related to other scientific fields with an emphasis on medical applications.

Radioisotopic purity and imaging properties of cyclotron-produced Tc using direct Mo(p,2n) reaction.

Evaluation of the radioisotopic purity of technetium-99m (Tc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (Mo) metallic targets at low proton energies (i.e. within 15-20 MeV) is conducted.

Technetium Complexes and Radiopharmaceuticals with Scorpionate Ligands.

Scorpionate ligands have played a crucial role in the development of technetium chemistry and, recently, they have also fueled important advancements in the discovery of novel diagnostic imaging agents based on the γ-emitting radionuclide technetium-99m. The purpose of this short review is to provide an illustration of the most general and relevant results in this field, however without being concerned with the details of the analytical features of the various compounds. Thus, emphasis will be given to the description of the general features of technetium complexes with scorpionate ligands including coordination modes, structural properties and an elementary bonding description.

14 MeV Neutrons for Mo/Tc Production: Experiments, Simulations and Perspectives.

Background: the gamma-emitting radionuclide Technetium-99m (Tc) is still the workhorse of Single Photon Emission Computed Tomography (SPECT) as it is used worldwide for the diagnosis of a variety of phatological conditions. Tc is obtained from Mo/Tc generators as pertechnetate ion, which is the ubiquitous starting material for the preparation of Tc radiopharmaceuticals. Mo in such generators is currently produced in nuclear fission reactors as a by-product of U fission.

Design and Synthesis of TcN-Labeled Dextran-Mannose Derivatives for Sentinel Lymph Node Detection.

Background: New approaches based on the receptor-targeted molecular interaction have been recently developed with the aim to investigate specific probes for sentinel lymph nodes. In particular, the mannose receptors expressed by lymph node macrophages became an attractive target and different multifunctional mannose derivate ligands for the labeling with Tc have been developed. In this study, we report the synthesis of a specific class of dextran-based, macromolecular, multifunctional ligands specially designed for labeling with the highly stable [Tc≡N] core.

In-house cyclotron production of high-purity Tc-99m and Tc-99m radiopharmaceuticals.

In the last years, the technology for producing the important medical radionuclide technetium-99m by cyclotrons has become sufficiently mature to justify its introduction as an alternative source of the starting precursor [Tc][TcO] ubiquitously employed for the production of Tc-radiopharmaceuticals in hospitals. These technologies make use almost exclusively of the nuclear reaction Mo(p,2n)Tc that allows direct production of Tc-99m. In this study, it is conjectured that this alternative production route will not replace the current supply chain based on the distribution of Mo/Tc generators, but could become a convenient emergency source of Tc-99m only for in-house hospitals equipped with a conventional, low-energy, medical cyclotron.

The emerging role of copper-64 radiopharmaceuticals as cancer theranostics.

Copper radionuclides are rapidly emerging as potential diagnostic and therapeutic tools in oncology, particularly Cu-radiopharmaceuticals for targeting neuroendocrine, prostate, and hypoxic tumors. Unexpectedly, experimental results are also revealing the impressive biological behavior of simple [Cu] ions. For example, it has been demonstrated that administration of ionic [Cu] in physiological solution allows the selective targeting of a variety of malignancies.

Comparison of 99mTc-UBI 29-41, 99mTc-ciprofloxacin, 99mTc-ciprofloxacin dithiocarbamate and 111In-biotin for targeting experimental Staphylococcus aureus and Escherichia coli foreign-body infections: an ex-vivo study.

Background: Diagnosis of implant-associated infection is challenging. Several radiopharmaceuticals have been described but direct comparisons are limited. Here we compared in vitro and in an animal model 99mTc-UBI, 99mTc-ciprofloxacin, 99mTcN-CiproCS2 and 111In-DTPA-biotin for targeting E.

A solvent-extraction module for cyclotron production of high-purity technetium-99m.

The design and fabrication of a fully-automated, remotely controlled module for the extraction and purification of technetium-99m (Tc-99m), produced by proton bombardment of enriched Mo-100 molybdenum metallic targets in a low-energy medical cyclotron, is here described. After dissolution of the irradiated solid target in hydrogen peroxide, Tc-99m was obtained under the chemical form of TcO, in high radionuclidic and radiochemical purity, by solvent extraction with methyl ethyl ketone (MEK). The extraction process was accomplished inside a glass column-shaped vial especially designed to allow for an easy automation of the whole procedure.