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99mTc-HYNIC-spermine for imaging polyamine transport system-positive tumours: preclinical evaluation

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Abstract

Purpose

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.

Conclusion

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.

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Authors and Affiliations

  1. Centre de Recherche en Oncologie Expérimentale, Institut de Recherche Pierre Fabre, Toulouse, France

    Sabrina Pesnel, Arnaud Pillon, Nicolas Guilbaud, Anna Kruczynski & Christian Bailly

  2. Division de Chimie Médicinale III, Institut de Recherche Pierre Fabre, Castres, France

    Yves Guminski & Thierry Imbert

  3. UPS n°44 TAAM – CIPA, CNRS, 3B rue de la Férollerie, 45071, Orléans, France

    Sabrina Pesnel, Stéphanie Lerondel & Alain Le Pape

  4. Université François Rabelais, INSERM U618, Tours, France

    Alain Le Pape

Authors
  1. Sabrina Pesnel
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  2. Yves Guminski
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  3. Arnaud Pillon
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  4. Stéphanie Lerondel
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  5. Thierry Imbert
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  6. Nicolas Guilbaud
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  7. Anna Kruczynski
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  8. Christian Bailly
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  9. Alain Le Pape
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Correspondence to Alain Le Pape.

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Pesnel, S., Guminski, Y., Pillon, A. et al. 99mTc-HYNIC-spermine for imaging polyamine transport system-positive tumours: preclinical evaluation. Eur J Nucl Med Mol Imaging 38, 1832–1841 (2011). https://doi.org/10.1007/s00259-011-1857-2

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  • DOI: https://doi.org/10.1007/s00259-011-1857-2

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