Molecular imaging of microbiota-gut-brain axis: searching for the right targeted probe for the right target and disease.

The highly bidirectional dialogue between the gut and the brain is markedly stimulated and influenced by the microbiome through integrated neuroendocrine, neurological and immunological processes. Gut microbiota itself communicate with the host producing hormonal intermediates, metabolites, proteins, and toxins responsible for a variety of biochemical and functional inputs, thereby shaping host homeostasis. Indeed, a dysregulated microbiota-gut-brain axis might be the origin of many neuroimmune-mediated disorders, e.

Biokinetic and dosimetric studies of 188Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma.

Unlabelled: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical.

Biodistribution imaging of a paclitaxel-hyaluronan bioconjugate.

Introduction: Gamma-ray detectors represent sensitive and noninvasive instruments to evaluate in vivo the metabolic trapping of radiopharmaceuticals. This study aimed to assess the imaging biodistribution of a [(99m)Tc]-radiolabelled new prototype bioconjugate composed of paclitaxel linked to hyaluronan (ONCOFID-P).

Methods: A small gamma camera providing high-resolution images was employed.

Detection of sites of infection in mice using 99mTc-labeled PN(2)S-PEG conjugated to UBI and 99mTc-UBI: a comparative biodistribution study.

Unlabelled: The antimicrobial peptide ubiquicidin (UBI) directly labeled with technetium-99m ((99m)Tc) has recently been shown to be specifically taken up at sites of infection; however, its chemical structure is not well defined. To address this problem, the aim of the present study was to label UBI using poly(ethyleneglycol)-N-(N-(3-diphenylphosphinopropionyl)glycyl)-S-tritylcysteine ligand (PEG-PN(2)S) in order to compare its ability to detect infection sites with that of (99m)Tc-UBI.

Methods: The PN(2)S-PEG-UBI conjugate was prepared and labeled with (99m)Tc, and its radiochemical purity was subsequently assessed.

A paclitaxel-hyaluronan bioconjugate targeting ovarian cancer affords a potent in vivo therapeutic activity.

Purpose: This study was designed to evaluate the pharmacologic and biological properties of a paclitaxel-hyaluronan bioconjugate (ONCOFID-P) against IGROV-1 and OVCAR-3 human ovarian cancer xenografts following i.p. administration.

Tris(1,2-dimethyl-3-hydroxy-4(1H)-pyridone)oxotantalum(v): a new water-soluble tantalum complex containing the [Ta=O]3+ core.

The synthesis, the characterization and the X-ray crystal structure of a novel tantalum(v) complex tris(1,2-dimethyl-3-hydroxy-4(1H)-pyridone)oxotantalum(v) [TaO(C7H8O2N)3] 1 is reported. Starting from the tantalum pentaethoxide a two-step reaction was carried out observing rigorous anhydrous conditions in methanol in the first step, while the insertion of the oxo group was achieved using water as oxygen donor in the second step. X-Ray diffraction analysis of a crystal of 1 obtained upon evaporation of an aqueous solution shows a seven-coordinate monomeric complex containing the [Ta=O]3+ core in the triclinic space group P1, a = 7.

Highly efficient technetium-99m labeling procedure based on the conjugation of N-[N-(3-diphenylphosphinopropionyl)glycyl]cysteine ligand with poly(ethylene glycol).

The PN(2)S N-(N-(3-diphenylphosphinopropionyl)glycyl)cysteine ligand was conjugated to methoxy-poly(ethylene glycol)-amino (mPEG-NH(2)) 5 and 20 kDa to yield PN(2)S(Trt)-PEG(5000) 1 and PN(2)S(Trt)-PEG(20000) 2, and then detritylated to PN(2)S-PEG(5000) 4 and PN(2)S-PEG(20000) 5. When an acidic solution of (99m)TcO(4)(-) is added to 4 or 5 in solid form, a quantitative yield in a single labeled species, (99m)Tc-labeled PN(2)S-PEG(5000) 9 and (99m)Tc-labeled PN(2)S-PEG(20000) 10, respectively, is obtained. The reaction occurs in less than 15 min at room temperature for 4 and 35 degrees C for 5.

Inhibition of hepatocellular carcinomas in vitro and hepatic metastases in vivo in mice by the histone deacetylase inhibitor HA-But.

Purpose: The purpose is to evaluate the CD44-mediated cellular targeting of HA-But, a hyaluronic acid esterified with butyric acid (But) residues, to hepatocellular carcinoma cell lines in vitro and to hepatic tumor metastases in vivo.

Experimental Design: In vitro, the CD44-dependent cytotoxicity in two human hepatocellular carcinoma cell lines (HepB3 and HepG2) with high and low CD44 expression was investigated; in vivo, the effect on liver metastases originating from intrasplenic implants of Lewis lung carcinoma (LL3) or B16-F10 melanoma in mice was compared with the pharmacokinetics of organ and tissue distribution using different routes of administration.

Results: HepB3 and HepG2 cell lines showed different expression of CD44 (78 and 18%, respectively), which resulted in a CD44-dependent HA-But inhibitory effect as demonstrated also by the uptake analysis performed using radiolabeled HA-But ((99m)Tc-HA-But).

Technetium-99m labeling of N-[N-(3-diphenylphosphino propionyl)glycyl]cysteine (PN2S-OH) and its methyl ester derivative (PN2S-OMe).

N-[N-(3-diphenylphosphinopropionyl)glycyl]cysteine and its methyl ester derivative were labeled with (99m)Tc at neutral pH, leading to a single species in high yield (>95%) in 30 min. RP-HPLC comparison with the analogue Re(V)-oxo complexes identified the labeled compounds as the anti isomers of pentacoordinated (99m)TcO[PN(2)S]-OH and (99m)TcO[PN(2)S]-OMe complexes. The compounds are stable from pH 7 to pH 9 when (99m)TcO[PN(2)S]-OH interconverts to related syn isomer, while (99m)TcO[PN(2)S]-OMe undergoes both saponification and interconversion.

Synthesis and characterization of rhenium(V) oxo complexes with N-[N-(3-diphenylphosphinopropionyl)glycyl]cysteine methyl ester. X-ray crystal structure of (ReO[Ph(2)P(CH(2))(2)C(O)-Gly-Cys-OMe(P,N,N,S)]).

The PN(2)S chelate N-[N-(3-diphenylphosphinopropionyl)glycyl]-S-tritylcysteine methyl ester [PN(2)S(Trt)-OMe] was synthesized and reacted with ReOCl(3)(PPh(3))(2) and Ph(4)P[ReOCl(4)]. The reactions of both tritylated and detritylated ligands with Re(V)O precursors gave two diastereomers, 9a and 9b, of the ReO(PN(2)S-OMe) complex. The two isomers, produced in a 1:1 molar ratio, are stable and do not interconvert.

CCK8 peptide derivatized with diphenylphosphine for rhenium labelling: synthesis and molecular mechanics calculations.

A novel CCK8 derivative bearing a chelating agent at its N- end and its oxo-rhenium(V) complex have been synthesized and characterized. The chelating agent N-[N-13-(diphenylphosphino)propionyl]glycyl]cysteine (PN2S) ligand, the coordination set of which is made by the phosphorus atom of phosphine, the nitrogen atoms of the two amido groups and the sulphur atom of cysteine, has been used due to its high affinity towards the oxo-rhenium(V) moiety. Molecular modelling studies indicate that the CCK8 peptide adopts the right conformation for cholecystokinin receptor binding, and that modifications on the N-terminal side of CCK8 obtained by introducing chelating agents and its metal complexes should not affect the interaction with CCK(A) receptor.

Radiochemical and biological characteristics of 99mTc-UBI 29-41 for imaging of bacterial infections.

A technetium-99m-labeled peptide derived from ubiquicidine, further referred to as 99mTc-UBI 29-41, targets bacterial and fungal infections, but not sterile inflammatory processes, in experimental animals. This paper reports on the radiochemical and biological features of this radioactive agent and the importance of the amino acid sequence of UBI 29-41 for imaging of infections. Radiochemical analyses of 99mTc-UBI 29-41 and a radiolabeled scrambled version of this peptide, i.

Technetium-99m labelled fluconazole and antimicrobial peptides for imaging of Candida albicans and Aspergillus fumigatus infections.

The aim of this study was to investigate whether technetium-99m labelled fluconazole can distinguish fungal from bacterial infections. Fluconazole was labelled with (99m)Tc and radiochemical analysis showed less than 5% impurities. The labelling solution was injected into animals with experimental infections.