EVALUATION OF DESFERAL AS A BIFUNCTIONAL CHELATING AGENT FOR LABELING ANTIBODIES WITH ZR-89

Zirconium-desferal was prepared and analysed by TLC, NMR and u.v.-spectroscopy. The stoichiometry of the complex was found to be 1:1. Chelation of desferal, coupled to resin, with Zr-88 appeared to be fast and almost quantitative in various buffer systems in a broad pH-range (4-7). A high in vitro stability of the zirconium-desferal complex was observed; less than 0.2% zirconium was lost within 24 h in plasma-solutions

Zirconium-labeled monoclonal antibodies and their distribution in tumor-bearing nude mice

A method to label monoclonal antibodies (MAbs) with Zr-88 and Zr-89 has been developed and tested on the MAbs 323/A3 and E48. Methods: The bifunctional chelating agent desferal (Df) was linked through a thioether bond to the Mabs. Labeling was accomplished by addition of the premodified antibodies to isolated Zr. The retention of the in vivo behavior of the MAbs was determined by comparing the biodistribution of Zr-88-labeled MAbs with those of I-123 and Tc-99m in mice bearing tumor xenografts. Results: The labeling was simple and the yields were high (above 90%). The obtained conjugates retained their immunoreactivity (>80). The blood clearance and biodistribution of Zr-labeled MAbs resembled those of the reference conjugates. The Zr-Df-MAb conjugates showed a specific tumor accumulation. Zirconium-89-labeled 323/A3 could be visualized with a PET camera. The absence of large amounts of Zr present in the bane pointed to a good in vivo stability of the Zr-Df-MAb conjugates. Conclusion: This method is well suited for labeling MAbs with Zr isotopes. Using Zr-89, the biodistribution of the radioimmunoconjugate can easily be visualized with a PET camera

PRODUCTION OF HIGHLY PURE NO-CARRIER ADDED ZR-89 FOR THE LABELING OF ANTIBODIES WITH A POSITRON EMITTER

Zr-89 was produced in high amounts (130 mCi/h) via a (p,n) reaction on Y-89. The Zr-89-isotope was purified using a hydroxamate column. More than 95% of the Zr was eluted with 1 mt of 1 M oxalic acid. The radionuclidic purity was over 99.99%. The isolated Zr-89 quantitatively formed complexes with the chelating agent desferal at low concentrations (10-100 mu M)

A facile method for the labeling of proteins with zirconium isotopes

To label proteins with positron emitters with a half life in the order of days, a method has been developed to label proteins with zirconium (Zr) isotopes. Therefore, the bifunctional chelating agent desferal (Df) was coupled to albumins via a thioether bond. Labeling of the premodified proteins was easily performed by addition of these proteins to freeze dried Zr-oxalate. This labeling was efficient (> 90%) and accomplished in several minutes. The conjugates showed a high in vitro stability. Biodistribution studies were performed with Zr-88-citrate, Zr-88-Df, and Zr-88-labeled mouse serum albumin (Zr-88,Df-MSA), modified with different amounts of chelating groups. Whereas Zr citrate was found to accumulate in bone, Zr Df was cleared very fast by glomerular filtration. The Zr-88-Df-MSA showed similar blood clearance as did I-123-labeled MSA. The biodistribution pattern of Zr-88-Df-MSA differed only from I-123-MSA in that a higher accumulation of Zr in liver, kidney, and spleen was found. The absence of large amounts of Zr-88 in bone indicated that in vivo the conjugates are also reasonably stable

Unconventional Nuclides for Radiopharmaceuticals

Rapid and widespread growth in the use of nuclear medicine for both diagnosis and therapy of disease has been the driving force behind burgeoning research interests in the design of novel radiopharmaceuticals. Until recently, the majority of clinical and basic science research has focused on the development of 11 C-, 13 N-, 15 O-, and 18 F-radiopharmaceuticals for use with positron emission tomography (PET) and 99m Tc-labeled agents for use with single-photon emission computed tomography (SPECT). With the increased availability of small, low-energy cyclotrons and improvements in both cyclotron targetry and purification chemistries, the use of “nonstandard” radionuclides is becoming more prevalent. This brief review describes the physical characteristics of 60 radionuclides, including β + , β −− , γ-ray, and α-particle emitters, which have the potential for use in the design and synthesis of the next generation of diagnostic and/or radiotherapeutic drugs. As the decay processes of many of the radionuclides described herein involve emission of high-energy γ-rays, relevant shielding and radiation safety issues are also considered. In particular, the properties and safety considerations associated with the increasingly prevalent PET nuclides 64 Cu, 68 Ga, 86 Y, 89 Zr, and 124 I are discussed