Preparation and evaluation of (89)Zr-Zevalin for monitoring of (90)Y-Zevalin biodistribution with positron emission tomography.
OBJECTIVE
To evaluate whether (89)Zr can be used as a PET surrogate label for quantification of (90)Y-ibritumomab tiuxetan ((90)Y-Zevalin) biodistribution and dosimetry before myeloablative radioimmunotherapy.


METHODS
Zevalin was labelled with (89)Zr by introducing N-succinyldesferal (N-sucDf) as a second chelate. For comparison of the in vitro stability of (89)Zr-Zevalin and (88)Y-Zevalin (as a substitute for (90)Y), samples were incubated in human serum at 37 degrees C up to 6 days. Biodistribution of (89)Zr-Zevalin and (88)Y-Zevalin was assessed at 24, 48, 72 and 144 h p.i. by co-injection in nude mice bearing the non-Hodgkin's lymphoma (NHL) xenograft line Ramos. The clinical performance of (89)Zr-Zevalin-PET was evaluated via a pilot imaging study in a patient with NHL, who had undergone [(18)F]FDG-PET 2 weeks previously.


RESULTS
Modification of Zevalin with N-sucDf resulted in an N-sucDf-to-antibody molar ratio of 0.83+/-0.04. After radiolabelling and purification, the radiochemical purity and immunoreactivity of (89)Zr-Zevalin always exceeded 95% and 80%, respectively. (89)Zr-Zevalin showed the same stability in serum as (88)Y-Zevalin, with a radiochemical purity >95% during a period of 6 days. The co-injected (89)Zr-Zevalin and (88)Y-Zevalin conjugates showed a very similar biodistribution, except for liver and bone accumulation at 72 and 144 h p.i., which was significantly higher for (89)Zr than for (88)Y. PET images obtained after injection of (89)Zr-Zevalin showed clear targeting of all known tumour lesions.


CONCLUSIONS
(89)Zr-Zevalin and (88)Y-Zevalin showed a very similar biodistribution in mice, implying that (89)Zr-Zevalin-PET might be well suited for prediction of (90)Y-Zevalin biodistribution in a myeloablative setting.
Perk
Lars R
LR
Department of Otolaryngology/Head and Neck Surgery, VU University Medical Centre, De Boelelaan 1117, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands.
Visser
Otto J
OJ
Stigter-van Walsum
M
M
Vosjan
Maria J W D
MJ
Visser
Gerard W M
GW
Zijlstra
Josée M
JM
Huijgens
Peter C
PC
van Dongen
Guus A M S
GA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D011868:Radioisotopes / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D014018:Tissue Distribution; D014915:Whole-Body Counting / Q000379:methods*; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015040:Zirconium / Q000493:pharmacokinetics*
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D015021:Yttrium Radioisotopes; C422802:ibritumomab tiuxetan; D015040:Zirconium