⁸⁶Y-labelled human serum albumin microspheres (DOTA-HSAM): In vivo stability depends on surface structure of the spheres

Introduction:

Radiolabelled particles are an attractive tool in the therapy of malignancies of the liver. We consider particles manufactured from denatured human serum albumin (HSAM) as useful carriers of therapeutic radionuclides, e.g. Y-90.

Experimental:

Two batches of HSAM (ROTOP Pharmaka GmbH; diameter: 20 – 30 μm) with smooth or rough surface, as determined by REM, were used for our studies. HSAM were functionalized by coupling DOTA via its isothiocyanate derivative in aqueous solution at pH 8.5 to lysine ε-amino groups on the surface of the spheres. Stability of Y-86 labelled DOTA-HSAM was investigated both in vitro (DTPA challenge) and in vivo (i. v. injection into the tail vein of healthy Wistar rats).

Results and Discussion:

Approximately 25 DOTA molecules per molecule HSA could be attached as estimated from elemental analysis of DOTA-HSAM. Y-86 labelling was performed under optimized conditions in 96 ± 1 % yield. No significant differences between smooth- and rough-surfaced HSAM were found for both, DOTA coupling and Y-86-labelling. In DTPA challenge experiments 98 ± 0 % of the radioactivity were still particle-associated after 24 hours incubation at 37 °C. In the in vivo experiments radiolabelled smooth and rough microspheres were completely trapped in the lungs. After 48 h the two batches differed significantly in their biodistribution pattern. For the clearance of radioactivity from the lungs decay-corrected half-lives of 85 h (rough microspheres) and 187 h (smooth microspheres) were calculated.

Conclusion:

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.