Preclinical evaluation of technetium 99m-labeled P1827DS for infection imaging and comparison with technetium 99m IL-8

Krause, Sabine; Rennen, Huub J.; Boerman, Otto C.; Baumann, Sabine; Cyr, John E.; Manchanda, Rajesh; Lister-James, John; Corstens, Frans C.; Dinkelborg, Ludger M.

doi:10.1016/j.nucmedbio.2007.07.016

« Previous Next »Nuclear Medicine and Biology
Volume 34, Issue 8 , Pages 925-932, November 2007

Preclinical evaluation of technetium 99m-labeled P1827DS for infection imaging and comparison with technetium 99m IL-8

Sabine Krause
- Bayer Schering Pharma AG, Global Drug Discovery, D-13342 Berlin, Germany
- Corresponding author. Tel.: +49 30 468 11476; fax: +49 30 468 91476.
Huub J. Rennen
- Radboud University, Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
Otto C. Boerman
- Radboud University, Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
Sabine Baumann
- Bayer Schering Pharma AG, Global Drug Discovery, D-13342 Berlin, Germany
John E. Cyr
- Bayer Schering Pharma AG, Global Drug Discovery, D-13342 Berlin, Germany
Rajesh Manchanda
- Bayer Schering Pharma AG, Global Drug Discovery, D-13342 Berlin, Germany
- Avid Radiopharmaceuticals, Philadelphia, PA, USA.
John Lister-James
- Bayer Schering Pharma AG, Global Drug Discovery, D-13342 Berlin, Germany
Frans C. Corstens
- Radboud University, Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
Ludger M. Dinkelborg
- Bayer Schering Pharma AG, Global Drug Discovery, D-13342 Berlin, Germany

Received 16 January 2007; received in revised form 31 May 2007; accepted 25 July 2007.

Abstract

Background

The technetium 99 m (^99mTc)-radiolabeled, leukocyte-avid peptide–glycoseaminoglycan complex, [^99mTc]P1827DS, has been synthesized as an improved infection/inflammation imaging agent to [^99mTc]P483H (LeukoTect, Diatide). In a phase I/II clinical trail, [^99mTc]P483H images were equivalent to those obtained with ¹¹¹In ex vivo labeled leukocytes. However, there was physiologic accumulation of radioactivity in the body that could hamper interpretation of the images. In this study, the potential of [^99mTc]P1827DS for infection imaging was assessed in comparison with [^99mTc]P483H and the well-described imaging agent [^99mTc] hydrazinonicotinamide (HYNIC)–interleukin 8 (IL-8).

Methods

The binding of [^99mTc]P1827DS to human blood cell was studied in vitro. A rabbit Escherichia coli infection model was used to perform the biodistribution and imaging studies with [^99mTc]P1827DS, [^99mTc]P483H and [^99mTc]HYNIC–IL-8.

Results

[^99mTc]P1827DS binds to leukocytes but not to erythrocytes. The leukocyte binding was not saturable up to an investigated concentration of 10 μM. The accumulation of [^99mTc]P1827/DS at the infection site strongly depends on the P1827/DS ratio and was optimal at a molar ratio of 10:1. [^99mTc]P1827DS shows improved biodistribution over [^99mTc]P483H with similar uptake at the infection site. Abscess uptake of [^99mTc]HYNIC–IL-8 was approximately three times higher than that of [^99mTc]P1827DS. [^99mTc]HYNIC–IL-8 showed high accumulation in the kidneys, whereas [^99mTc]P1827DS showed high lung uptake and slightly higher accumulation in the liver and spleen.

Conclusion

[^99mTc]P1827DS is a potential new inflammation imaging agent, which clearly visualized the abscess in the rabbit E. coli infection model and showed improved biodistribution compared to [^99mTc]P483H. However, the infection uptake and biodistribution of [^99mTc]P1827DS is not superior to that of [^99mTc]HYNIC–IL-8 in this animal model.

Keywords: Peptide, SPECT, Imaging, Infection, Inflammation, Technetium-99m