title: 99mTc-HYNIC-spermine for imaging polyamine transport system-positive tumours: preclinical evaluation.
abstract: OBJECTIVE
  F14512 exploiting the polyamine transport system (PTS) for tumour cell delivery has been described as a potent antitumour agent. The optimal use of this compound will require a probe to identify tumour cells expressing a highly active PTS that might be more sensitive to the treatment. The aim of this study was to design and characterize a scintigraphic probe to evaluate its uptake in cancer cells expressing the PTS.
  
  
  METHODS
  Three polyamines coupled to a hydrazinonicotinamide (HYNIC) moiety were synthesized and labelled with 99mTc. Their radiochemical purity was determined by HPLC. The plasma stability of the 99mTc-HYNIC-spermine probe and its capacity to accumulate into PTS-active cells were also evaluated. In vitro internalization was tested using murine melanoma B16/F10 cells and human lung carcinoma A549 cells. Biodistribution was determined in healthy mice and tumour uptake was studied in B16/F10 tumour-bearing mice. A HL-60-Luc human leukaemia model was used to confront single photon emission computed tomography (SPECT) images obtained with the 99mTc-labelled probe with those obtained by bioluminescence.
  
  
  RESULTS
  The 99mTc-HYNIC-spermine probe was selected for its capacity to accumulate into PTS-active cells and its stability in plasma. In vitro studies demonstrated that the probe was internalized in the cells via the PTS. In vivo measurements indicated a tumour to muscle scintigraphic ratio of 7.9±2.8. The combined bioluminescence and scintigraphic analyses with the leukaemia model demonstrated that the spermine conjugate accumulates into the tumour cells.
  
  
  CONCLUSIONS
  The 99mTc-HYNIC-spermine scintigraphic probe is potentially useful to characterize the PTS activity of tumours. Additional work is needed to determine if this novel conjugate may be useful to analyse the PTS status of patients with solid tumours.
authors.affiliation: Centre de Recherche en Oncologie Expérimentale, Institut de Recherche Pierre Fabre, Toulouse, France, sabrina.pesnel@cnrs-orleans.fr
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pesnel
authors.forename: Yves
authors.initials: Y
authors.lastname: Guminski
authors.forename: Arnaud
authors.initials: A
authors.lastname: Pillon
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lerondel
authors.forename: Thierry
authors.initials: T
authors.lastname: Imbert
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guilbaud
authors.forename: Anna
authors.initials: A
authors.lastname: Kruczynski
authors.forename: Christian
authors.initials: C
authors.lastname: Bailly
authors.forename: Alain
authors.initials: A
authors.lastname: Le Pape
mesh_terms: D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004355:Drug Stability; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D011854:Radiochemistry; D013096:Spermine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D002352:Carrier Proteins; D006834:Hydrazines; D015609:Organotechnetium Compounds; C117288:hydrazino nicotinamide; C569025:technetium 99m HYNIC-spermine; D009536:Niacinamide; D013096:Spermine