Yttrium-86-labelled human serum albumin microspheres: relation of surface structure with in vivo stability

Schiller, Eik; Bergmann, Ralf; Pietzsch, Jens; Noll, Bernhard; Sterger, Antje; Johannsen, Bernd; Wunderlich, Gerd; Pietzsch, Hans-Jürgen

doi:10.1016/j.nucmedbio.2007.10.008

« Previous Next »Nuclear Medicine and Biology
Volume 35, Issue 2 , Pages 227-232, February 2008

Yttrium-86-labelled human serum albumin microspheres: relation of surface structure with in vivo stability

Eik Schiller
- ROTOP Pharmaka AG, Bautzner Landstraße 45, 01454 Radeberg, Germany
- Corresponding author. Tel.: +493512603461; fax: +493512603232.
Ralf Bergmann
- Forschungszentrum Dresden-Rossendorf, Institute of Radiopharmacy, P.O. Box 510119, 01314 Dresden, Germany
Jens Pietzsch
- Forschungszentrum Dresden-Rossendorf, Institute of Radiopharmacy, P.O. Box 510119, 01314 Dresden, Germany
Bernhard Noll
- Forschungszentrum Dresden-Rossendorf, Institute of Radiopharmacy, P.O. Box 510119, 01314 Dresden, Germany
Antje Sterger
- ROTOP Pharmaka AG, Bautzner Landstraße 45, 01454 Radeberg, Germany
Bernd Johannsen
- ROTOP Pharmaka AG, Bautzner Landstraße 45, 01454 Radeberg, Germany
Gerd Wunderlich
- Department of Nuclear Medicine, University Hospital, Fetscherstraße 74, 01307 Dresden, Germany
Hans-Jürgen Pietzsch
- Forschungszentrum Dresden-Rossendorf, Institute of Radiopharmacy, P.O. Box 510119, 01314 Dresden, Germany

Received 12 September 2007; received in revised form 12 October 2007; accepted 22 October 2007. published online 17 December 2007.

Abstract

Introduction

Radiolabelled particles are an attractive tool in the therapy of malignancies of the liver. We consider particles manufactured from denatured human serum albumin (HSA) as useful carriers of therapeutic radionuclides. Covalent attachment of suitable chelators onto the surface of the spheres promises an easy access to radiolabelled HSA microspheres.

Methods

We synthesized 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA) bearing smooth, medium-rough and rough surfaced HSA microspheres (mean diameter: 25 μm). In vitro stability of ⁸⁶Y-labelled particles was determined after incubation in human plasma and in a DTPA challenge experiment. In vivo stability of ⁸⁶Y DOTA-HSA microspheres was determined after single intravenous application in rats. Subsequently, the particles were completely trapped in the lung microvasculature. Thus, the lung serves in our experiments as target organ.

Results

DOTA-HSA microspheres were ⁸⁶Y labelled in reproducible high yields (>95%). No differences between smooth and rough surfaced spheres were found for both DOTA coupling and ⁸⁶Y labelling. Labelled microspheres showed high in vitro stability in human plasma and in DTPA solution with only 8±1% and 2±0% loss of radioactivity from the surface, respectively, 48 h postinjection (pi). The three batches (smooth, medium-rough and rough surfaced microspheres) differed considerably in their radioactivity recovery in the lungs of rats 48 h pi. Smooth particles showed the highest in vivo stability of the radiolabel on the surface of the spheres, presumably because of slower proteolytic degradation.

Conclusion

We found that for the preparation of HSA-derived microspheres for radiotherapeutic application, smooth surfaced spheres are superior to rough spheres due to their higher in vivo stability of the radionuclide fixation.

Keywords: Human serum albumin microspheres, Yttrium-86, In vivo stability, Radiolabelled particles, Radiotherapy