Radionuclides linked to a CD74 antibody as therapeutic agents for B-cell lymphoma: Comparison of auger electron emitters with β-particle emitters

S. V. Govindan, D. M. Goldenberg, S. E. Elsamra, G. L. Griffiths, Lin Ong Gaik Lin Ong, M. W. Brechbiel, J. Burton, G. Sgouros, M. J. Mattes

Research output: Contribution to journalArticlepeer-review

Abstract

We demonstrated previously that human B-cell lymphomas were effectively and specifically killed in vitro by an antibody to CD74 (LL1) linked to 111In or other Auger electron emitters. This study was intended to more accurately compare the potency and specificity of 3 Auger electron emitters, 111In, 67Ga, and 125I, and to evaluate β-particle emitters, 131I and 90Y. The unique property of LL1 is its high level of intracellular uptake. Methods: Raji B-lymphoma cells were incubated with serial dilutions of the radiolabeled Abs for 2 d and then monitored for cell growth by 2 assays: a cell counting assay and a clonogenic assay. The uptake of radioactivity per cell was monitored at vadous time points, and the radiation dose was calculated using published S values for radioactivity located in the cytoplasm. Both specific and nonspecific toxicity were evaluated. Results: The β-particle emitters had considerably higher levels of nonspecific toxicity than the Auger electron emitters, but both 131I and 90Y, and particularly 131I, still had high levels of specificity. Both of these results were consistent with dosimetry calculations. Relative to the delivered disintegrations per cell, 131I and 67Ga were the most potent of the radionuclides tested, with 125I and 111In being significantly weaker and 90Y being intermediate. The high potency of 67Ga, together with its low nonspecific toxicity, caused this radionuclide to have the highest specificity index. Conclusion: When delivered by Ab LL1, both Auger electron and β-particle emitters can produce specific and effective toxicity. The choice of the optimal radionuclide for therapy may depend on the ease and efficiency of labeling, the specific activity obtained, the nature of the tumor being targeted, and other factors, but the high specificity indices of the Auger electron emitters may be an advantage.

Original languageEnglish (US)
Pages (from-to)2089-2097
Number of pages9
JournalJournal of Nuclear Medicine
Volume41
Issue number12
StatePublished - 2000
Externally publishedYes

Keywords

  • AntiCD74 antibody
  • B-cell lymphoma
  • In vitro cytotoxicity
  • Radiolabeled Abs

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'Radionuclides linked to a CD74 antibody as therapeutic agents for B-cell lymphoma: Comparison of auger electron emitters with β-particle emitters'. Together they form a unique fingerprint.

Cite this