Position paper to facilitate patient access to radiopharmaceuticals: considerations for a suitable pharmaceutical regulatory framework.

Background: Nuclear medicine has made enormous progress in the past decades. However, there are still significant inequalities in patient access among different countries, which could be mitigated by improving access to and availability of radiopharmaceuticals.

Main Body: This paper summarises major considerations for a suitable pharmaceutical regulatory framework to facilitate patient access to radiopharmaceuticals.

Gold-Enhanced Brachytherapy by a Nanoparticle-Releasing Hydrogel and 3D-Printed Subcutaneous Radioactive Implant Approach.

Brachytherapy (BT) is a widely used clinical procedure for localized cervical cancer treatment. In addition, gold nanoparticles (AuNPs) have been demonstrated as powerful radiosensitizers in BT procedures. Prior to irradiation by a BT device, their delivery to tumors can enhance the radiation effect by generating low-energy photons and electrons, leading to reactive oxygen species (ROS) production, lethal to cells.

A Three-Dimensional Printable Hydrogel Formulation for the Local Delivery of Therapeutic Nanoparticles to Cervical Cancer.

Cervical cancer is the fourth most common malignancy among women. Compared to other types of cancer, therapeutic agents can be administrated locally at the mucosal vaginal membrane. Thermosensitive gels have been developed over the years for contraception or for the treatment of bacterial, fungal, and sexually transmitted infections.

Messenger RNA of and Genes as Monitoring Markers of Clear Cell Renal Adenocarcinoma (a Pilot Study).

Unlabelled: was to assess the capabilities of mRNA genes encoding CD16a () and CD16b () in tumor samples from patients with renal cancer, and characterize the tumor process in relation to clinical and morphological factors.

Materials And Methods: We used 125 tumor samples from patients with a histologically confirmed diagnosis of renal cancer TNM. A method described by Chomczynski and Sacchi was used to isolate nucleic acids.

Fifty Years of Radiopharmaceuticals.

To celebrate the 50th anniversary of the founding of the SNMMI Technologist Section in 1970, the Radiopharmaceutical Sciences Council board of directors is pleased to contribute to this celebratory supplement of the with a perspective highlighting major developments in the radiopharmaceutical sciences that have occurred in the last 50 years.

Serum Protein Corona Abolishes Changes in the Expression of Proinflammatory Genes Induced by Quantum Dots in Human Blood Mononuclear Cell.

We studied changes in the transcription of genes encoding cytokines (TNF, IL-6, IL-10, and IL-32), cell activation markers (ICAM1, CD38, Fas, and FCGRIII), ROS production catalyst (NOX2), autophagy (Beclin 1, LC3B, and p62) and apoptosis (BAX, BCL2) regulators in peripheral blood mononuclear cells upon contact with quantum dots CdSe/ZnS-MPA and CdSe/CdSeZnS/ZnS-PTVP. Up-regulation of TNF, ICAM1, Fas, p62 mRNA and down-regulation of the FCGRIII and NOX2 mRNA in response to the presence of quantum dots were revealed. The formation of serum protein corona on the surface of quantum dots abolished this effect.

Robust high-yield ~1 TBq production of cyclotron based sodium [Tc]pertechnetate.

Unlabelled: This paper presents the irradiation and processing of high-current Mo targets at the University of Alberta (UofA) in a GMP compliant setting. For purpose of comparison with a second production facility, additional studies at Centre Hospitalier Universitaire de Sherbrooke (CHUS) are also described.

Introduction: More than 70% of today's diagnostic radiopharmaceuticals are based on Tc, however the conventional supply chain for obtaining Tc is fragile.

Clinical Trial with Sodium Tc-Pertechnetate Produced by a Medium-Energy Cyclotron: Biodistribution and Safety Assessment in Patients with Abnormal Thyroid Function.

A single-site prospective open-label clinical study with cyclotron-produced sodium Tc-pertechnetate (Tc-NaTcO) was performed in patients with indications for a thyroid scan to demonstrate the clinical safety and diagnostic efficacy of the drug and to confirm its equivalence with conventional Tc-NaTcO eluted from a generator. Tc-NaTcO was produced from enriched Mo (99.815%) with a cyclotron (24 MeV; 2 h of irradiation) or supplied by a commercial manufacturer (bulk vial eluted from a generator).

[ANTIOXIDANT THERAPY FOR INFERTILE COUPLES].

This study presents results of 113 infertile couples treated with supplements speroton and pregnoton containing folic acid, L-carnitine, vitamin E, zinc, and other vitamins and minerals. Infertility in couples was due to both the pathology of spermatogenesis, and female genital diseases. It has been demonstrated that intake of Speroton restores impaired motility in the ejaculate of patients with several forms of pathospermia, and Pregnoton ensure its preservation in vaginal secretions.

Radioisotopic Purity of Sodium Pertechnetate 99mTc Produced with a Medium-Energy Cyclotron: Implications for Internal Radiation Dose, Image Quality, and Release Specifications.

Unlabelled: Cyclotron production of 99mTc is a promising route to supply 99mTc radiopharmaceuticals. Higher 99mTc yields can be obtained with medium-energy cyclotrons in comparison to those dedicated to PET isotope production. To take advantage of this capability, evaluation of the radioisotopic purity of 99mTc produced at medium energy (20-24 MeV) and its impact on image quality and dosimetry was required.

Synthesis and pharmacological evaluation of ¹¹C-labeled piperazine derivative as a PET probe for sigma-2 receptor imaging.

Introduction: Both subtypes of sigma (σ) receptors, σ₁ and σ₂, are over-expressed in many cancers with σ₂ proposed as a biomarker of tumor proliferation. We are interested in developing a high affinity selective σ₂ radioligand for in vivo monitoring of proliferative status of solid tumors and response to anti-cancer therapies. 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) represents one of the lead candidates in the development of σ receptor ligands for therapeutic and diagnostic applications.

In vitro and in vivo evaluation of N-{2-[4-(3-Cyanopyridin-2-yl)piperazin-1-yl]ethyl}-3-[(11) C]methoxybenz-amide, a positron emission tomography (PET) radioligand for dopamine D4 receptors, in rodents.

The D4 dopamine receptor belongs to the D2 -like family of dopamine receptors, and its exact regional distribution in the central nervous system is still a matter of considerable debate. The availability of a selective radioligand for the D4 receptor with suitable properties for positron emission tomography (PET) would help resolve issues of D4 receptor localization in the brain, and the presumed diurnal change of expressed protein in the eye and pineal gland. We report here on in vitro and in vivo characteristics of the high-affinity D4 receptor-selective ligand N-{2-[4-(3-cyanopyridin-2-yl)piperazin-1-yl]ethyl}-3-[(11) C]methoxybenzamide ([(11) C]2) in rat.

[Efficiency of spematon in male infertility].

The article presents the results of the application of spematon in 39 men from infertile couples with different forms of pathospermia (asthenozoospermia, oligozoospermia, teratozoospermia). It is shown that the effect in the first 3 months of use of spematon is mainly associated with normalization of acrosome reaction of sperm cells. It was established that spematon, due to content of L-carnitine content, zinc, vitamin E, contributes restoration of induction of acrosome reaction.

Gene expression levels of matrix metalloproteinases in human atherosclerotic plaques and evaluation of radiolabeled inhibitors as imaging agents for plaque vulnerability.

Introduction: Atherosclerotic plaque rupture is the primary cause for myocardial infarction and stroke. During plaque progression macrophages and mast cells secrete matrix-degrading proteolytic enzymes, such as matrix metalloproteinases (MMPs). We studied levels of MMPs and tissue inhibitor of metalloproteinases-3 (TIMP-3) in relation to the characteristics of carotid plaques.

Synthesis and biological evaluation of ¹⁸F-labeled fluoropropyl tryptophan analogs as potential PET probes for tumor imaging.

In the search for an efficient, fluorine-18 labeled amino acid based radiotracer for tumor imaging with positron emission tomography (PET), two new tryptophan analogs were synthesized and characterized in vitro and in vivo. Both are tryptophan alkyl-derivatives, namely 2-(3-[(18)F]fluoropropyl)-DL-tryptophan ([(18)F]2-FPTRP) and 5-(3-[(18)F]fluoro-propyl)-DL-tryptophan ([(18)F]5-FPTRP). Standard reference compounds and precursors were prepared by multi step approaches.

Development of 3,4-dihydroisoquinolin-1(2H)-one derivatives for the Positron Emission Tomography (PET) imaging of σ₂ receptors.

σ₂ Receptors are promising biomarkers for cancer diagnosis given the relationship between the proliferative status of tumors and their density. With the aim of contributing to the research of σ₂ receptor Positron Emission Tomography (PET) probes, we developed 2-[3-[6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl]propyl]-3,4-dihydroisoquinolin-1(2H)-one (3), with optimal σ₂ pharmacological properties and appropriate lipophilicity. Hence, 3 served as the lead compound for the development of a series of dihydroisoquinolinones amenable to radiolabeling.

Studies toward the development of new silicon-containing building blocks for the direct (18)F-labeling of peptides.

Silicon-containing prosthetic groups have been conjugated to peptides to allow for a single-step labeling with (18)F radioisotope. The fairly lipophilic di-tert-butylphenylsilane building block contributes unfavorably to the pharmacokinetic profile of bombesin conjugates. In this article, theoretical and experimental studies toward the development of more hydrophilic silicon-based building blocks are presented.

Design, synthesis, and initial evaluation of a high affinity positron emission tomography probe for imaging matrix metalloproteinases 2 and 9.

The activity of matrix metalloproteinases (MMPs) is elevated locally under many pathological conditions. Gelatinases MMP2 and MMP9 are of particular interest because of their implication in angiogenesis, cancer cell proliferation and metastasis, and atherosclerotic plaque rupture. The aim of this study was to identify and develop a selective gelatinase inhibitor for imaging active MMP2/MMP9 in vivo.

Synthesis and evaluation of biphenyl compounds as kinesin spindle protein inhibitors.

Kinesin spindle protein (KSP), an ATP-dependent motor protein, plays an essential role in bipolar spindle formation during the mitotic phase (M phase) of the normal cell cycle. KSP has emerged as a novel target for antimitotic anticancer drug development. In this work, we synthesized a range of new biphenyl compounds and investigated their properties in vitro as potential antimitotic agents targeting KSP expression.

[To question about integrated prevention of diabetes taking into account the technogenic factors of environment (experimental results)].

Experimental conditions shown that formaldehyde decreased course of diabetes. Adding to meal the powder of plant's rhizome Curcuma longa contributes to the restoration of the morphological structure of the liver, kidney, the normalization of water-salt and carbohydrate metabolism, this can be used in programs for integrated prevention of diabetes in areas of technological risk.

Single-step radiofluorination of peptides using continuous flow microreactor.

18F radiolabelling of peptides bearing two different prosthetic groups was successfully conducted in a continuous flow microfluidic device for the first time. Radiochemical yields were dependent on precursor concentration, reaction temperature and flow rate. The choice of leaving group had a dramatic influence on the reaction outcome.

Radiofluorinated histamine H₃ receptor antagonist as a potential probe for in vivo PET imaging: radiosynthesis and pharmacological evaluation.

The histamine H(3) receptor (H(3)R) plays a role in cognition and memory processes and is implicated in different neurological disorders, including Alzheimer's disease, schizophrenia, and narcolepsy. In vivo studies of the H(3)R occupancy using a radiolabeled PET tracer would be very useful for CNS drug discovery and development. We report here the radiosynthesis, in vitro and in vivo evaluation of a novel (18)F-labeled high-affinity H(3)R antagonist (18)F-ST889.

The synthesis and properties of new 2-pyrrolylthiones as chelating agents for transition metals and technetium.

A series of new 2-pyrrolylthiones was synthesized and found to be good chelating agents for transition metals and technetium.