Evaluation of 177Lu[Lu]-CHX-A″-DTPA-6A10 Fab as a radioimmunotherapy agent targeting carbonic anhydrase XII

Nucl Med Biol. 2018 May;60:55-62. doi: 10.1016/j.nucmedbio.2018.02.004. Epub 2018 Mar 4.


Introduction: Due to their infiltrative growth behavior, gliomas have, even after surgical resection, a high recurrence tendency. The approach of intracavitary radioimmunotherapy (RIT) is aimed at inhibiting tumor re-growth by directly administering drugs into the resection cavity (RC). Direct application of the radioconjugate into the RC has the advantage of bypassing the blood-brain barrier, which allows the administration of higher radiation doses than systemic application. Carbonic anhydrase XII (CA XII) is highly expressed on glioma cells while being absent from normal brain and thus an attractive target molecule for RIT. We evaluated a CA XII-specific 6A10 Fab (fragment antigen binding) labelled with 177Lu as an agent for RIT.

Methods: 6A10 Fab fragment was modified and radiolabelled with 177Lu and characterized by MALDI-TOF, flow cytometry and radio-TLC. In vitro stability was determined under physiological conditions. Biodistribution studies, autoradiography tumor examinations and planar scintigraphy imaging were performed on SCID-mice bearing human glioma xenografts.

Results: The in vitro CA XII binding capacity of the modified Fab was confirmed. Radiochemical purity was determined to be >90% after 72 h of incubation under physiological conditions. Autoradiography experiments proved the specific binding of the Fab to CA XII on tumor cells. Biodistribution studies revealed a tumor uptake of 3.0%ID/g after 6 h and no detectable brain uptake. The tumor-to-contralateral ratio of 10/1 was confirmed by quantitative planar scintigraphy.

Conclusion: The radiochemical stability in combination with a successful in vivo tumor uptake shows the potential suitability for future RIT applications with the 6A10 Fab.

Keywords: (177)Lu; Carbonic anhydrase XII; Fab; Glioblastoma; Radioimmunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Carbonic Anhydrases / metabolism*
  • Female
  • Humans
  • Immunoconjugates / chemistry
  • Immunoconjugates / pharmacokinetics
  • Immunoconjugates / therapeutic use
  • Immunoglobulin Fab Fragments / chemistry*
  • Immunoglobulin Fab Fragments / metabolism
  • Immunoglobulin Fab Fragments / therapeutic use*
  • Lutetium*
  • Mice
  • Pentetic Acid / chemistry*
  • Radiochemistry
  • Radioimmunotherapy / methods*
  • Radioisotopes*
  • Tissue Distribution


  • Immunoconjugates
  • Immunoglobulin Fab Fragments
  • Radioisotopes
  • Lutetium
  • Pentetic Acid
  • Lutetium-177
  • Carbonic Anhydrases
  • carbonic anhydrase XII