Molecular Imaging and Biology

, Volume 14, Issue 6, pp 725–734 | Cite as

In Vivo pH Imaging with 99mTc-pHLIP

  • Sven Macholl
  • Matthew S. Morrison
  • Peter Iveson
  • Bente E. Arbo
  • Oleg A. Andreev
  • Yana K. Reshetnyak
  • Donald M. Engelman
  • Edvin Johannesen
Research Article
First Online:

Abstract

Purpose

A novel molecular imaging agent has been developed recently, which stains tissues of low extracellular pH [pH (low) insertion peptide, pHLIP®]. A pH-dependent process of peptide folding and insertion into cell membranes has been found in vitro. Targeting of acidic solid tumours has been demonstrated in vivo using fluorescence and PET labels. Here, we present proof of feasibility studies of pHLIP with a single-photon emission computed tomography (SPECT) label, 99mTc-AH114567, with focus on preclinical efficacy and imageability.

Procedures

Lewis lung carcinoma, lymph node carcinoma of the prostate and prostate adenocarcinoma tumour xenografts were grown in mice and characterised by the angiogenesis marker 99mTc-NC100692 and by extracellular pH measurements with 31P-MRS of 3-aminopropyl phosphonate. Biodistribution was assessed and CT/SPECT imaging performed. Oral administration of bicarbonate served as control.

Results and Conclusion

Tc-AH114567 can be obtained via a robust synthesis with good radiolabelling profile and improved formulation. The tracer retains the pH-dependent ability to insert into membranes and to target tumours with similar pharmacokinetics and efficacy that had been demonstrated earlier for pHLIP with optical or 64Cu PET labels. Despite the inherent challenges of SPECT compared to optical and PET imaging, e.g., in terms of lower sensitivity, 99mTc-AH114567 shows adequate image quality and contrast. The main development need for transitioning SPECT labelled pHLIP into the clinic is more rapid background signal reduction, which will be the focus of a subsequent optimisation study.

Key words

Molecular imaging pHLIP Tc-99m SPECT Extracellular pH AH114567 3-APP Maraciclatide Preclinical 
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Notes

Acknowledgements

We thank Willy Gsell, David Herlihy, Magdy Mohamed Khalil, Jordi Lopez-Tremoleda and Marzena Wylezinska-Arridge (Biological Imaging Centre at Imperial College, London) for excellent imaging support and colleagues at GEHC for their technical support and fruitful discussions. Thanks to Clifford Smith (GEHC) for suggesting and supporting this project.

Conflict of Interest Disclosure

S.M., P.I., M.S.M., B.E.A., and E.J. are paid employees of GE Healthcare. O.A.A., Y.K.R. and D.M.E. are consultants for GE Healthcare.

Supplementary material

11307_2012_549_MOESM1_ESM.pdf (201 kb)
ESM 1 (PDF 201 kb)

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Copyright information

© World Molecular Imaging Society 2012

Authors and Affiliations

  • Sven Macholl
    • 1
  • Matthew S. Morrison
    • 1
  • Peter Iveson
    • 1
  • Bente E. Arbo
    • 2
  • Oleg A. Andreev
    • 3
  • Yana K. Reshetnyak
    • 3
  • Donald M. Engelman
    • 4
  • Edvin Johannesen
    • 2
  1. 1.Medical Diagnostics, The Grove CentreGE HealthcareAmershamUK
  2. 2.Medical DiagnosticsGE HealthcareOsloNorway
  3. 3.Physics DepartmentUniversity of Rhode IslandKingstonUSA
  4. 4.Department of Molecular Biophysics and BiochemistryNew HavenUSA

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