RCY

This study describes the synthesis, radiofluorination and purification of an anionic amphiphilic teroligomer developed as a stabilizer for siRNA-loaded calcium phosphate nanoparticles (CaP-NPs). As the stabilizing amphiphile accumulates on nanoparticle surfaces, the fluorine-18-labeled polymer should enable to track the distribution of the CaP-NPs in brain tumors by positron emission tomography after application by convection-enhanced delivery. At first, an unmodified teroligomer was synthesized with a number average molecular weight of 4550 ± 20 Da by free radical polymerization of a defined composition of methoxy-PEG-monomethacrylate, tetradecyl acrylate and maleic anhydride...

(-)-Epigallocatechin gallate (EGCG), a key component of green tea, exerts therapeutic anticancer and antiallergic properties through its binding to the 67 kDa laminin receptor. The functionalization of EGCG is a promising strategy for creating new drug candidates and chemical probes. In our study, we developed a method for effectively modifying the A ring of EGCG through an electrophilic aromatic substitution with amidomethyl 2-alkynylbenzoates initiated with a gold complex. The 2-alkynylbenzoates treated with (Ph3 P)AuOTf under neutral conditions yielded N -acylimines...

BACKGROUND: The [177 Lu]Lu-DOTA-TATE mediated peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs) is sometimes leading to treatment resistance and disease recurrence. An interesting alternative could be the somatostatin antagonist, [177 Lu]Lu-DOTA-JR11, that demonstrated better biodistribution profile and higher tumor uptake than [177 Lu]Lu-DOTA-TATE. Furthermore, treatment with alpha emitters showed improvement of the therapeutic index of PRRT due to the high LET offered by the alpha particles compared to beta emitters...

Radiochemical yields (RCYs) of isotope exchange-based 18 F-fluorination of non-carbon-centered substrates in water are rationally enhanced by adding surfactants, which increases both the rate constant k and local reactant concentrations. Among 12 surfactants, the cationic surfactant cetrimonium bromide (CTAB) and two nonionic surfactants (Tween 20 and Tween 80) were selected for their superior catalytic effects, namely, electrostatic effects or solubilization effects. For a model substrate, bis(4-methoxyphenyl)phosphinic fluoride, the 18 F-fluorination rate constant ( k ) increased up to 7-fold, while its saturation concentration rose up to 15-fold due to micelle formation, encapsulating 70-94% of the substrate...

Objective  The incidence of inoperable hepatocellular carcinoma (HCC) with/without malignant portal vein thrombosis (PVT) is increasing in India for the last decade; thus, Bhabha Atomic Research Centre (BARC), Mumbai, India, developed diethydithiocarbamate (DEDC), a new transarterial radionuclide therapy (TART) agent. 188 Re-N-DEDC lipiodol is an emerging radiotherapeutic agent for inoperable HCC treatment due to its simple and onsite labeling procedure, cost-effectiveness, and least radiation-induced side effects...

BACKGROUND: [18 F]AlF-NOTA-octreotide is an 18 F-labeled somatostatin analogue which is a good clinical alternative for 68 Ga-labeled somatostatin analogues. However, radiolabeled somatostatin receptor (SSTR) antagonists might outperform agonists regarding imaging sensitivity of neuroendocrine tumors (NETs). No direct comparison between the antagonist [18 F]AlF-NOTA-JR11 and the agonist [18 F]AlF-NOTA-octreotide as SSTR PET probes is available. Herein, we present the radiosynthesis of [18 F]AlF-NOTA-JR11 and compare its NETs imaging properties directly with the established agonist radioligand [18 F]AlF-NOTA-octreotide preclinically...

Clinical studies have demonstrated that the γ-aminobutyric acid type A (GABAA ) receptor complex plays a central role in the modulation of anxiety. Conditioned fear and anxiety-like behaviors have many similarities at the neuroanatomical and pharmacological levels. The radioactive GABA/BZR receptor antagonist, fluorine-18-labeled flumazenil, [18 F]flumazenil, behaves as a potential PET imaging agent for the evaluation of cortical damage of the brain in stroke, alcoholism, and for Alzheimer disease investigation...

Availability of PET imaging radiotracers targeting α-synuclein aggregates is important for early diagnosis of Parkinson's disease and related α-synucleinopathies, as well as for the development of new therapeutics. Derived from a pyrazole backbone, 11 C-labelled derivatives of anle138b (3-(1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1 H -pyrazole)-an inhibitor of α-synuclein and prion protein oligomerization-are currently in active development as the candidates for PET imaging α-syn aggregates...

We have developed a diphosphine (DP) platform for radiolabeling peptides with 99m Tc and 64 Cu for molecular SPECT and PET imaging, respectively. Two diphosphines, 2,3-bis(diphenylphosphino)maleic anhydride (DPPh ) and 2,3-bis(di- p -tolylphosphino)maleic anhydride (DPTol ), were each reacted with a Prostate Specific Membrane Antigen-targeted dipeptide (PSMAt) to yield the bioconjugates DPPh -PSMAt and DPTol -PSMAt, as well as an integrin-targeted cyclic peptide, RGD, to yield the bioconjugates DPPh -RGD and DPTol -RGD...

Recently, retinoid actions on the central nervous system (CNS) have attracted considerable attention from the perspectives of brain disease diagnosis and drug development. Firstly, we successfully synthesized [11 C]peretinoin esters (methyl, ethyl, and benzyl) using a Pd(0)-mediated rapid C-[11 C]methylation of the corresponding stannyl precursors without geometrical isomerization in 82%, 66%, and 57% radiochemical yields (RCYs). Subsequent hydrolysis of the 11 C-labeled ester produced [11 C]peretinoin in 13 ± 8% RCY (n = 3)...

Background: CXCR3 is a chemokine receptor and is expressed on innate and adaptive immune cells. It promotes the recruitment of T-lymphocytes and other immune cells to the inflammatory site in response to the binding of cognate chemokines. Upregulation of CXCR3 and its chemokines has been found during atherosclerotic lesion formation. Therefore, the detection of CXCR3 by positron emission tomography (PET) radiotracer may be a useful tool to detect atherosclerosis development noninvasively. Herein, we report the synthesis, radiosynthesis, and characterization of a novel fluorine-18 (F-18, 18 F) labeled small-molecule radiotracer for the imaging of the CXCR3 receptor in mouse models of atherosclerosis...

INTRODUCTION: Thorium-226 is a promising radioisotope for radioimmunotherapy. Here, we have prepared two "in-house" 230Pa/230U/226Th tandem generators consisting of an anion exchanger AG 1x8 and extraction chromatographic sorbent TEVA resin. METHOD: Developed "direct" generators resulted in the production of 226Th with high yield and purity as required for biomedical applications. Next, we prepared Nimotuzumab radioimmunoconjugates with thorium-234, a long-living analog of 226Th, using bifunctional chelating agents (BFCAs) p-SCN-Bn-DTPA and p-SCN-Bn-DOTA...

[18 F]FTC-146 was introduced as a very potent and selective sigma-1 receptor radioligand, which has shown promising application as an imaging agent for neuropathic pain with positron emission tomography. In line with a multi-laboratory project on animal welfare, we chose this radioligand to investigate its potential for detecting neuropathic pain and tissue damage in tumor-bearing animals. However, the radiochemical yield (RCY) of around 4-7% was not satisfactory to us and efforts were made to improve it. Herein, we describe an improved approach for the radiosynthesis of [18 F]FTC-146 resulting in a RCY, which is 7-fold higher than that previously reported...

Overexpression of the NLRP3 inflammasome has been attributed to the progressive worsening of a multitude of cardiovascular inflammatory diseases such as myocardial infarction, pulmonary arterial hypertension, and atherosclerosis. The recently discovered potent and selective NLRP3 inhibitor MCC950 has shown promise in hindering disease progression, but NLRP3-selective cardiovascular positron emission tomography (PET) imaging has not yet been demonstrated. We synthesized [11 C]MCC950 with no-carrier-added [11 C]CO2 fixation chemistry using an iminophosphorane precursor (RCY 45 ± 4%, >99% RCP, 27 ± 2 GBq/μmol, 23 ± 3 min, n = 6) and determined its distribution both in vivo and ex vivo in C57BL/6 and atherogenic ApoE -/- mice...

[18 F]F-DOPA is widely used in PET diagnostics. Diseases diagnosed with this tracer are schizophrenia, Parkinson's disease, gliomas, neuroendocrine tumors, pheochromocytomas, and pancreatic adenocarcinoma. It should be noted that the [18 F]F-DOPA tracer has been known for over 30 years. However, the methods of radiosynthesis applied in the past did not allow its clinical use due to low efficiency and purity. Currently, in the market, one encounters different types of radiosynthesis using the fluorine 18 F isotope and variants of the same method...

Positron emission tomography (PET) is a highly valuable imaging technique with many clinical applications. The possibility to study physiological and biochemical processes in vivo also makes PET an important tool in drug discovery. Of importance is the possibility of labelling the compound of interest with a positron-emitting radionuclide, such as carbon-11. Carbonylation reactions with [11 C]carbon monoxide ([11 C]CO) has been used to label a number of molecules containing a carbonyl derivative, such as amides and esters, with carbon-11...

Integrins are cell surface receptors involved in multiple functions vital for cellular proliferation. Various tumor cells overexpress αβ-integrins, making them ideal biomarkers for diagnostic imaging and tumor-targeted drug delivery. LXY30 is a peptide that can specifically recognize and interact with the integrin α3 β1 , a molecule overexpressed in breast, ovarian and colorectal cancer. Hepatitis E virus nanoparticles (HEVNPs) are virus-like particles that have been investigated as drug delivery agents for the targeted delivery of nucleic acids and small proteins...

BACKGROUND: Radiopharmaceuticals are considered as regular medicinal products and therefore the same regulations as for non-radioactive medicinal products apply. However, specific aspects should be considered due to the radiochemical properties. Radiopharmaceutical dedicated monographs are developed in the European Pharmacopoeia to address this. Currently, different quality control methods for non-registered radiopharmaceuticals are utilized, often focusing on radio-TLC only, which has its limitations...

Epidermal growth factor receptors (EGFR) of tyrosine kinase (TK) have shown high expression levels in most cancers and are considered a promising target for cancer diagnosis and therapy. Expanding the investigation for novel targeted radiopharmaceuticals, an EGFR inhibitor such as 4-aminoquinazoline derivatives along with a radionuclide such as technetium-99m (99m Tc) could be ideal. Thus, we report herein the synthesis, characterization, and biological evaluation of new "4 + 1" mixed-ligand ReIII - and 99m TcIII -complexes of the general formula [99m Tc][Tc(NS3 )(CN-R)] bearing tris(2-mercaptoethyl)-amine (NS3 ) as the tetradentate tripodal ligand and a series of isocyanide derivatives (CN-R) of tyrosine kinase inhibitor (3-bromophenyl)quinazoline-4,6-diamine as the monodentate ligand...

BACKGROUND: Manganese porphyrins have several therapeutic/imaging applications, including their use as radioprotectants (in clinical trials) and as paramagnetic MRI contrast agents. The affinity of porphyrins for lipid bilayers also makes them candidates for cell/liposome labelling. We hypothesised that metalation with the positron emission tomography (PET) radionuclide 52 Mn (t1/2  = 5.6 d) would allow long-term in vivo biodistribution studies of Mn-porphyrins, as well as a method to label and track cells/liposomes, but methods for fast and efficient radiolabelling are lacking...