Characterization of a radiolabeled small molecule targeting leukocyte function-associated antigen-1 expression in lymphoma and leukemia

Rahul B. Poria, Jeffrey P. Norenberg, Tamara L. Anderson, Jack Erion, Carston R. Wagner, Jeffrey B. Arterburn, Richard S. Larson

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Objective: Leukocyte function-associated antigen-1 (LFA-1) is constitutively expressed on leukocytes, including overexpression on lymphomas and leukemias. We have developed a derivative of BIRT 377, an allosteric inhibitor of LFA-1, which may be chemically tagged without affecting binding. In this study, we modified this derivative, (R)-1-(4-aminobutyl)-5-(4-bromobenzyl) -3-(3,5-dichlorophenyl)-5-methylimidazolidine-2,4-dione (butylamino-NorBIRT), and demonstrated its potential as a noninvasive imaging agent. Methods: Specific binding of fluorescein-labeled butylamino-NorBIRT to both human and murine cells was demonstrated using equilibrium binding and dissociation techniques. A radiometal, lutetium-177 (Lu-177), was incorporated into the butylamino-NorBIRT through 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA) as a chelator. Results: Equilibrium-binding experiments demonstrated that fluorescein-labeled butylamino-NorBIRT specifically binds human and murine LFA-1 with affinity constants of 135 and 186 nM, respectively. Dissociation kinetic experiments demonstrated an off-rate of 0.168/second -1 on murine cells, consistent with the observed affinity constant. Lutetium-177 was used for labeling, with ≥99.99% radiochemical purity and incorporation yield. This radiolabeled derivative exhibited high stability in fetal bovine serum (FBS) at 37°C over 72 hours. 177Lu-DOTA- butylamino-NorBIRT showed a binding affinity of 235 nM to human LFA-1 for equilibrium binding and competitive binding experiments. Conclusions: The radiolabeled DOTA-butylamino-NorBIRT may have potential as a noninvasive imaging or therapeutic agent in both human and mouse models.

Original languageEnglish (US)
Pages (from-to)418-426
Number of pages9
JournalCancer Biotherapy and Radiopharmaceuticals
Issue number5
StatePublished - 2006


  • Butylamino-NorBIRT
  • Leukocyte function-associated antigen-1
  • Lutetium-177
  • Lymphoma
  • Radionuclide imaging


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