Lu-Labeled Iron Oxide Nanoparticles Functionalized with Doxorubicin and Bevacizumab as Nanobrachytherapy Agents against Breast Cancer.

The use of conventional methods for the treatment of cancer, such as chemotherapy or radiotherapy, and approaches such as brachytherapy in conjunction with the unique properties of nanoparticles could enable the development of novel theranostic agents. The aim of our current study was to evaluate the potential of iron oxide nanoparticles, coated with alginic acid and polyethylene glycol, functionalized with the chemotherapeutic agent doxorubicin and the monoclonal antibody bevacizumab, to serve as a nanoradiopharmaceutical agent against breast cancer. Direct radiolabeling with the therapeutic isotope Lutetium-177 (Lu) resulted in an additional therapeutic effect.

New Imaging Modality of COVID-19 Pneumonia Developed on the Basis of Alzheimer's Disease Research.

Viral pneumonia caused by highly infectious SARS-CoV-2 poses a higher risk to older people and those who have underlying health conditions, including Alzheimer's disease. In this work we present newly designed tacrine-based radioconjugates with physicochemical and biological properties that are crucial for the potential application as diagnostic radiopharmaceuticals. A set of ten tacrine derivatives was synthesized, labelled with gallium-68 and fully characterized in the context of their physicochemical properties.

In Vitro Biological Evaluation of Aprepitant Based Lu-Radioconjugates.

Currently, the search for promising NK1R-positive tumor-targeting radiopharmaceuticals based on the structure of small molecular antagonists of neurokinin-1 receptor can be observed. Following this trend, we continued our evaluation of aprepitant-based Lu-radioconjugates in terms of future oncological applications. For this purpose, three novel aprepitant homologues were synthesized to broaden the previously obtained derivative portfolio, functionalized with the DOTA chelator and labeled with Ga and Lu.

Novel NK1R-Targeted Ga-/Lu-Radioconjugates with Potential Application against Glioblastoma Multiforme: Preliminary Exploration of Structure-Activity Relationships.

Locoregionally administered, NK1 receptor (NK1R) targeted radionuclide therapy is a promising strategy for the treatment of glioblastoma multiforme. So far, the radiopharmaceuticals used in this approach have been based on the endogenous agonist of NK1R, Substance P or on its close analogues. Herein, we used a well-known, small molecular NK1R antagonist, L732,138, as the basis for the radiopharmaceutical vector.

Physicochemical and Biological Study of Tc and Ga Radiolabelled Ciprofloxacin and Evaluation of [Tc]Tc-CIP as Potential Diagnostic Radiopharmaceutical for Diabetic Foot Syndrome Imaging.

This paper presents the application of ciprofloxacin as a biologically active molecule (vector) for delivering diagnostic radiopharmaceuticals to the sites of bacterial infection. Ciprofloxacin-based radioconjugates containing technetium-99m or gallium-68 radionuclides were synthesised, and their physicochemical (stability, lipophilicity) and biological (binding study to and ) properties were investigated. Both the tested radiopreparations met the requirements for radiopharmaceuticals, and technetium-99m-labelled ciprofloxacin turned out to be a good radiotracer for the tomography of diabetic foot syndrome using SPECT.

Common Shortcomings in Study on Radiopharmaceutical Design Research: A Case Study of Tc-Labelled Methotrexate.

The aim of the work carried out was to draw attention to shortcomings that often appear at the stage of designing new radiopharmaceuticals. Based on a case study of Tc-labelled methotrexate, this article describes frequent mistakes or misconceptions present not only in the referenced studies, but also in numerous radiopharmaceutical studies. The recommendations provided in this article highlight fundamental aspects of the credibility of radiopharmaceutical scientific research leading to the reliable results.

Synthesis and In Vitro Evaluation of Gold Nanoparticles Functionalized with Thiol Ligands for Robust Radiolabeling with Tc.

Radiolabeled gold nanoparticles (AuNPs) have been widely used for cancer diagnosis and therapy over recent decades. In this study, we focused on the development and in vitro evaluation of four new Au nanoconjugates radiolabeled with technetium-99m (Tc) via thiol-bearing ligands attached to the NP surface. More specifically, AuNPs of two different sizes (2 nm and 20 nm, referred to as Au and Au, respectively) were functionalized with two bifunctional thiol ligands (referred to as LH and LH).

Perspectives of Methotrexate-Based Radioagents for Application in Nuclear Medicine.

Methotrexate is a gold standard among disease modifying antirheumatic drugs and is also extensively used clinically in combination with oncological therapies. Thus, it is not surprising that nuclear medicine found an interest in methotrexate in the search for diagnostic and therapeutic solutions. Numerous folate-related radiopharmaceuticals have been proposed for nuclear medicine purposes; however, methotrexate radioagents represent only a minority.

Radiochemical Synthesis and Evaluation of Novel Radioconjugates of Neurokinin 1 Receptor Antagonist Aprepitant Dedicated for NK1R-Positive Tumors.

Aprepitant, a lipophilic and small molecular representative of neurokinin 1 receptor antagonists, is known for its anti-proliferative activity on numerous cancer cell lines that are sensitive to Substance P mitogen action. In the presented research, we developed two novel structural modifications of aprepitant to create aprepitant conjugates with different radionuclide chelators. All of them were radiolabeled with Ga and Lu radionuclides and evaluated in terms of their lipophilicity and stability in human serum.

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers.

Methotrexate, a structural analogue of folic acid, is one of the most effective and extensively used drugs for treating many kinds of cancer or severe and resistant forms of autoimmune diseases. In this paper, we take an overview of the present state of knowledge with regards to complex mechanisms of methotrexate action and its applications as immunosuppressive drug or chemotherapeutic agent in oncological combination therapy. In addition, the issue of the potential benefits of methotrexate in the development of neurological disorders in Alzheimer's disease or myasthenia gravis will be discussed.

Synthesis, physicochemical and biological evaluation of tacrine derivative labeled with technetium-99m and gallium-68 as a prospective diagnostic tool for early diagnosis of Alzheimer's disease.

Design, physicochemical and biological studies of novel radioconjugates for the early diagnosis of Alzheimer's disease, based on the newly synthesized tacrine derivatives were performed. Novel tacrine analogues were labeled with technetium-99m and gallium-68. For all obtained radioconjugates ([Tc]Tc-Hynic-(tricine)NH(CH)tacrine and [Ga]Ga-DOTA-NH(CH)tacrine, where n = 2-9 denotes the number of methylene groups CH) the studies of physicochemical properties (lipophilicity, stability in the presence of an excess of standard amino acids cysteine or histidine, human serum and in cerebrospinal fluid) were performed.

Application of Neurokinin-1 Receptor in Targeted Strategies for Glioma Treatment. Part I: Synthesis and Evaluation of Substance P Fragments Labeled with Tc and Lu as Potential Receptor Radiopharmaceuticals.

Gliomas, particularly WHO grade IV glioblastoma multiforme, are one of the most common and aggressive primary tumors of the central nervous system. The neuropeptide, substance P (SP), is the physiological ligand of the neurokinin-1 (NK-1) receptor that is consistently overexpressed in glioblastoma cells. The aim of this work was to study physico-chemical and biological properties of different SP analogues labeled with technetium-99m and lutetium-177 radionuclides.

Nanozeolite bioconjugates labeled with Ra for targeted alpha therapy.

Introduction: Alpha particle emitting isotopes are of considerable interest for radionuclide therapy because of their high cytotoxicity and short path length. Among the many α emitters, Ra exhibits very attractive nuclear properties for application in radionuclide therapy. The decay of this radioisotope and its daughters is accompanied by the emission of four α-particles, releasing 27.

Synthesis, physicochemical and biological studies of technetium-99m labeled tacrine derivative as a diagnostic tool for evaluation of cholinesterase level.

In the present work the synthesis and physicochemical investigations of new tacrine analogues labeled with technetium-99m are reported. All obtained novel radioconjugates showed high stability in the presence of an excess of standard amino acids cysteine or histidine, as well as in human serum. Lipophilicity (LogD values) of these compounds is within the range from 0.

Synthesis, physicochemical and biological evaluation of technetium-99m labeled lapatinib as a novel potential tumor imaging agent of Her-2 positive breast cancer.

Tumors that are Her-2-positive tend to grow and spread more quickly than other types of breast cancer. Overexpression of Her-2 can be a predictive biomarker for stratification of patients for therapy with Herceptin (containing humanized IgG1 monoclonal antibody trastuzumab) or Tykerb (containing lapatinib di-p-toluenesulfonate) drug. Usually, Her-2 status is determined by immunohistochemical (IHC) as well as fluorescent or chromogenic in situ hybridisation (FISH or CISH) analysis of biopsy material.

Synthesis and in vitro/in vivo evaluation of novel mono- and trivalent technetium-99m labeled ghrelin peptide complexes as potential diagnostic radiopharmaceuticals.

Introduction: Ghrelin is an endogenous hormone present in blood. It is released from the oxyntic cells (X/A-like cells) of the stomach and fundus and can exist in two forms: as an acylated and des-acylated ghrelin. Ghrelin is an endogenous ligand of the growth hormone receptor (growth hormone secretagogue receptor, GHS-R).

99mTc-labeled vasopressin peptide as a radiopharmaceutical for small-cell lung cancer (SCLC) diagnosis.

The 99mTc-labeled conjugates of the vasopressin (AVP) peptide and of its analogue d(CH2)5[D-Tyr(Et2)-Ile4-Eda9]AVP (AVP(an)) have been synthesized using the technetium complexes with tetradentate tripodal chelator (the tris(2-mercaptoethyl)amine (NS3)) and the monodentate isocyanide ligand (CN-peptide). The conjugates exhibit high stability in the presence of 100 times the molar excess of standard amino acids cysteine or histidine and also satisfactory stability in human serum. The 99mTc(NS3)(CN-AVP) and 99mTc(NS3)(CN-AVP(an)) ability of binding to small-cell lung cancer (SCLC) cell line H69 was studied in vitro.

Impact of functionalized coligands on the pharmacokinetics of 99mTcIII '4+1' mixed-ligand complexes conjugated to bombesin.

Bombesins (BN) containing (99m)Tc '4+1' complexes may be useful to detect tumors expressing the gastrin-releasing peptide receptor (GRPR). Derivatives of the formula [(99m)Tc(NS(3)R)(L2-BN(st))] were synthesized, in which Tc(III) is coordinated by an isocyanide L2-BN(st) bearing the peptide (BN(st)=βAla-βAla-Gln-Trp-Ala-Val-Gly-His-Cha-Nle-NH(2)) and a tetradentate chelator NS(3)R. NS(3)R consists of 2,2',2″-nitrilotriethanethiol (NS(3)) bearing a crown ether (NS(3)crown), an aliphatic amine (NS(3)en) and a tricarboxylic acid (NS(3)(COOH)(3)).

'2+1' tricarbonyltechnetium(I)/tricarbonylrhenium(I) mixed-ligand complexes with methyl thiosalicylate and isocyanide ligands as potential precursors of radiopharmaceuticals.

The complexes of [(99m)Tc]-tricarbonyltechnetium(I) and [(188)Re]-tricarbonylrhenium(I), of the '2+1' type, with methyl thiosalicylate as an anionic bidentate ligand and with either tert-butyl 3-isocyanopropionate or glycine-glycine-tyrosine 4-isocyanobutyrate as monodentate ligands, have been prepared on the n.c.a.

Batch-injection stripping voltammetry (tube-less flow-injection analysis) of trace metals with on-line sample pretreatment.

The most essential limitation of batch-injection analysis (BIA) methodology compared to other flow methods (CFA, FIA, SIA) is the lack of possibility of on-line sample processing in the measuring system. Some procedures of on-line sample pretreatment in BIA are possible by changing the plastic tip of the automatic micropipette used for sample injection into a flow-through reactor, e.g.