title: Preparation and first biological evaluation of novel Re-188/Tc-99m peptide conjugates with substance-P.
abstract: BACKGROUND
  New (188)Re and (99m)Tc peptide conjugates with substance- P (SP) were prepared and biologically evaluated. The radiopharmaceuticals have been labelled with the [M≡N](2+) (M=(99m)Tc, (188)Re) core using a combination of π-donor tridentate and π-acceptor monodentate ancillary ligands.
  
  
  METHODS
  The new radiopharmaceuticals have been prepared through a two-step reaction by simultaneous addition of the tridentate and monodentate ligands to a vial containing a preformed [M≡N](2+) core. The tridentate ligand was formed by linking two cysteine residues to the terminal arginine of the undecapeptide SP, whereas the monodentate ligand was a tertiary phosphine. The preparation of the corresponding Re-188 derivative required developing a more complex chemical procedure to obtain the [Re≡N](2+) core in satisfactory yields. Characterization of the resulting products was obtained by chromatographic methods. Biological evaluation was performed for both Tc-99m and Re-188 derivatives by in-vitro studies on isolated cells expressing NK1-receptors. In-vivo imaging in mice was carried out using a small-animal YAP(S)PET tomograph.
  
  
  CONCLUSIONS
  New Tc-99m and Re-188 peptide radiopharmaceuticals with SP have been prepared in high-yield and with high-specific activity. Both Tc-99m and Re-188 peptide radioconjugates exhibit high affinity for NK1 receptors, thus giving further evidence to the empirical rule that structurally related Tc-99m and Re-188 radiopharmaceuticals exhibit identical biological properties.
authors: Faculty of Medical Sciences, University 'Goce Delcev', Stip, Macedonia.
authors: Katarina
authors: K
authors: Smilkov
authors: Faculty of Medical Sciences, University 'Goce Delcev', Stip, Macedonia.
authors: Emilija
authors: E
authors: Janevik
authors: Department of Chemical and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, Italy.
authors: Remo
authors: R
authors: Guerrini
authors: Laboratory of Nuclear Medicine, Department of Experimental Medicine, University of Ferrara, Via L. Borsari, 46, 44121 Ferrara, Italy.
authors: Micol
authors: M
authors: Pasquali
authors: Laboratory of Nuclear Medicine, Department of Experimental Medicine, University of Ferrara, Via L. Borsari, 46, 44121 Ferrara, Italy.
authors: Alessandra
authors: A
authors: Boschi
authors: Laboratory of Nuclear Medicine, Department of Experimental Medicine, University of Ferrara, Via L. Borsari, 46, 44121 Ferrara, Italy.
authors: Licia
authors: L
authors: Uccelli
authors: Faculty of Medical Sciences, University 'Goce Delcev', Stip, Macedonia; Department of Chemical and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, Italy; Laboratory of Nuclear Medicine, Department of Experimental Medicine, University of Ferrara, Via L. Borsari, 46, 44121 Ferrara, Italy.
authors: Giovanni
authors: G
authors: Di Domenico
authors: Laboratory of Nuclear Medicine, Department of Experimental Medicine, University of Ferrara, Via L. Borsari, 46, 44121 Ferrara, Italy. Electronic address: adriano.duatti@unife.it.
authors: Adriano
authors: A
authors: Duatti
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004355:Drug Stability; D007553:Isotope Labeling / Q000379:methods; D008657:Metabolic Clearance Rate; D051379:Mice; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism*; D009928:Organ Specificity; D011868:Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D012211:Rhenium / Q000737:chemistry* / Q000493:pharmacokinetics*; D013373:Substance P / Q000737:chemistry / Q000493:pharmacokinetics*; D013667:Technetium / Q000737:chemistry* / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; D013373:Substance P; D012211:Rhenium; D013667:Technetium
keywords: Metal nitrido radiopharmaceuticals; Peptide radiopharmaceuticals; Rhenium-188; Substance-P; Technetium-99m