Comparison of the stability of Y-90-, Lu-177- and Ga-68- labeled human serum albumin microspheres (DOTA-HSAM).
BACKGROUND
Microparticles derived from denatured human serum albumin (DOTA-derivatized human serum albumin microspheres, or DOTA-HSAM) are attractive carriers of radionuclides for both therapeutic and diagnostic purposes. In this article, we describe a labeling procedure for diagnostic (Ga-68) and therapeutic (Y-90, Lu-177) radionuclides and report on the results of stability studies of these products.


METHODS
DOTA-HSAM was labeled in 0.5 M ammonium acetate buffer, pH 5.0, containing 0.02 mg/ml detergent. After adding the radionuclide, the mixture was shaken for 15 min at 90°C. Labeling yields and in vitro stability were determined by thin-layer chromatography. For determination of the in vivo stability of Ga-68 and Y-90 DOTA-HSAM, the particles were injected intravenously in Wistar rats.


RESULTS
Labeling yields up to 95% in the case of Ga-68 and Lu-177 were achieved. Ga-68-labeled DOTA-HSAM showed high in vitro and in vivo stability. The amount of particle-bound radioactivity of Lu-177 DOTA-HSAM declines slowly in a linear manner to approximately 72% after 13 days. For Y-90, the labeling yield decreased with increasing radioactivity level. We presume radiolysis as the reason for these findings.


CONCLUSIONS
The labeling of DOTA-HSAM with different radionuclides is easy to perform. The radiation-induced cleavage of the labeled chelator together with the rather short half-life of radioactivity fixation in vivo (3.7 days) is, in our opinion, opposed to therapeutic applications of DOTA-HSAM. On the other hand, the high stability of Ga-68 DOTA-HSAM makes them an attractive candidate for the measurement of regional perfusion by PET.
Department of Nuclear Medicine, University Hospital, 01307 Dresden, Germany.
Gerd
G
Wunderlich
Eik
E
Schiller
Ralf
R
Bergmann
Hans-Jürgen
HJ
Pietzsch
D000818:Animals; D004355:Drug Stability; D005710:Gallium Radioisotopes / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D007700:Kinetics; D008187:Lutetium / Q000737:chemistry* / Q000627:therapeutic use; D008297:Male; D008863:Microspheres; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000737:chemistry* / Q000493:pharmacokinetics; D015021:Yttrium Radioisotopes / Q000737:chemistry* / Q000627:therapeutic use
D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D012709:Serum Albumin; D015021:Yttrium Radioisotopes; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D008187:Lutetium