Journal of Nuclear Science, Engineering and Technology (JONSAT)
In cooperation with the Iranian Nuclear Society

Radiolabeling Quality Control and Biodistribution Study of Anti-CD20 Antibody by 67Ga

Document Type : Research Paper

Authors

A.R Jalilian
L Mirsadeghi
A Khorrami
S Moradkhani
B Naserian
S Daneshvari
N Shadanpour
H Ghahreman
R Haji-Hosseini
Abstract
Nowadays, anti-CD20 antibodies are being used in the therapy of lymphomas in free or radiolabeled form. Conjugation process was performed using native antibody and DOTA-NHS compound, synthesized in our laboratory. Thin layer chromatography and gel filtration were used to control the reaction progress as well as purification of the final antibody conjugate. 67GaCl3 produced at AMIRS was used to label the immunoconjugate and the reaction conditions were optimized for time, temperature and reactant concentrations. Quality control of the radioimmunoconjugate was performed using RTLC and gel filtration. The radiochemical purity was shown to be over 95%. The radioimmunoconjugate was used in the biodistribution studies up to 28 h and it was shown that after 24h most of the activity was accumulated in reticuloendothelial system consisting liver and spleen.

Highlights

  1. 1.    T.E. Witzig, C.A. White, G.A. Wiseman, L.I. Gordon, C. Emmanouilides, A. Raubitschek, N. Janakiraman, J. Gutheil, R.J. Schilder, S. Spies, D.H. Silverman, E. Parker, A.J. Grillo-Lopez, “Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin's lymphoma,” J. Clin. Oncol. 17, 3793–3803 (1999).

 

  1. 2.    J.F. Eary, O.W. Press, C.C. Badger, L.D. Durack, K.Y. Richter, S.J. Addison, K.A. Krohn, D.R. Fisher, B.A. Porter, D.L. Williams DL, et al, “Imaging and treatment of B-cell lymphoma,” J. Nucl. Med. 31, 1257–1268 (1990).

 

  1. 3.    S.J. Knox, R. Levy, R.A. Miller, W. Uhland, J. Schiele, W. Ruehl, R. Finston, P. Day-Lollini, M.L. Goris, “Determinants of the antitumor effect of radiolabeled monoclonal antibodies,” Cancer Res. 50, 4935-4940 (1990).

 

  1. 4.    R.A. Kyle, M.A. Gertz, P.R. Greipp, T.E. Witzig, J.A. Lust, M.Q. Lacy, T.M. Therneau, “Long-term survival (10 years or more) in 30 patients with primary amyloidosis,” Blood, 93(3), 1062-1066 (1999).

 

  1. 5.    M. Dietlein, H. Pels, H. Schulz, O. Staak, P. Borchmann, K. Schomäcker, T. Fischer, W. Eschner, E.P. von Strandmann, H. Schicha, A. Engert, R. Schnell, “Imaging of central nervous system lymphomas with iodine-123 labeled rituximab,” Eur. J. Haematol. 74, 348-352 (2005).

 

  1. 6.    J. Hoffend, W. Mier, J. Schuhmacher, K. Schmidt, A. Dimitrakopoulou-Strauss, L.G. Strauss, M.E.R. Kinscherf, U. Haberkorna, “Gallium-68-DOTA-albumin as a PET blood-pool marker: experimental evaluation in vivo,” Nucl. Med. Biol. 32, 287–292 (2005).

 

  1. 7.    O. Ugur, P.J. Kothari, R.D. Finn, P. Zanzonico, S. Ruan, I. Guenther, H.R. Maecke, S.M. Larson, “Ga-66 labeled somatostatin analogue DOTA-DPhe1-Tyr3-octreotide as a potential agent for positron emission tomography imaging and receptor mediated internal radiotherapy of somatostatin receptor positive tumors,” Nucl. Med. Biol. 29, 147–157 (2002).

 

  1. 8.    M.R. McDevitt, D.Ma,J. Simon, R.K. Frank, D.A. Scheinberg, “Design and synthesis of 225Ac radioimmun opharmaceuticals,”  Applied Radiat. Isot. 57, 841–847 (2002).
  2. 9.    C.J. Smith, H. Gali, G.L. Sieckman, D.L. Hayes, N.K. Owen, D.G. Mazuru, W.A. Volkert, T.J. Hoffman, “Radiochemical investigations of 177Lu-DOTA-8-Aoc-BBN[7-14] NH2: an in vitro/in vivo assessment of the targeting ability of this new radiopharmaceutical for PC-3 human prostate cancer cells,” Nucl. Med. Biol. 30, 101–109 (2003).

 

  1. 10.              L.L. Chappell, E. Dadachova, D.E. Milenic, K. Garmestani, C.Wu, M.W. Brechbiel, “Synthesis, Characterization, and Evaluation of a Novel Bifunctional Chelating Agent for the Lead Isotopes 203Pb and 212Pb,” Nucl. Med. & Biol. 27, 93–100 (2000).

 

11. S. Banerjee, T. Das, S. Chakraborty, G. Samuel, A. Korde, S. Srivastava, M. Venkatesha, M.R.A. Pillai, “177Lu-DOTA-lanreotide: A novel tracer as a targeted agent for tumor therapy,” Nucl. Med. Biol. 31, 753–759 (2004).

 

12. W. Mier, J. Hoffend, S. Kramer, J. Schuhmacher, W.E. Hull, M. Eisenhut,  “Conjugation of DOTA using isolated phenolic active esters: The labeling and biodistribution of albumin as a blood-pool marker,” Bioconjug. Chem. 16, 237–240 (2005).

 

13. U. Pandey, A. Mukherjee, H.D. Sarma, T. Das, M.R.A. Pillai, M. Venkatesh, “Evaluation of 90Y-DTPA and 90Y-DOTA for potential application in intra-vascular radionuclide therapy,” Appl. Rad. Isot. 57, 313-318 (2002).

 

  1. 14.              P. Goethals, M. Coene, G. Slegers, D. Vogelaers, J. Everaert, I. Lemahieu, F. Colardyn, G.R. Heyndrickx, “Production of carrier-free 66Ga and labeling of antimyosin antibody for positron imaging of acute myocardial infarction,” Eur. J. Nucl. Med. 16, 237-240 (1990).

 

  1. 15.              J. Kowalski, M. Henze, J. Schuhmacher, H.R. Macke, M. Hofmann, U. Haberkorn. “Evaluation of positron emission tomography imaging using [68Ga]-DOTA-D Phe(1)-Tyr(3)-Octreotide in comparison to [111In]-DTPAOC SPECT. First results in patients with neuroendocrine tumors,” Mol. Imaging Biol. 5(1), 42-48 (2003).

 

16. U.K. Laemmli, “Cleavage of structural proteins during assembly of the head of the bacteriophage T4,” Nature (London),227, 680–685 (1970).

Keywords

Anti-CD20
DOTA
67Ga
Rituximab
Cyclotron
Quality Control
Biodistribution
Labeling
Radioisotope Production
  1. 1.    T.E. Witzig, C.A. White, G.A. Wiseman, L.I. Gordon, C. Emmanouilides, A. Raubitschek, N. Janakiraman, J. Gutheil, R.J. Schilder, S. Spies, D.H. Silverman, E. Parker, A.J. Grillo-Lopez, “Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin's lymphoma,” J. Clin. Oncol. 17, 3793–3803 (1999).

 

  1. 2.    J.F. Eary, O.W. Press, C.C. Badger, L.D. Durack, K.Y. Richter, S.J. Addison, K.A. Krohn, D.R. Fisher, B.A. Porter, D.L. Williams DL, et al, “Imaging and treatment of B-cell lymphoma,” J. Nucl. Med. 31, 1257–1268 (1990).

 

  1. 3.    S.J. Knox, R. Levy, R.A. Miller, W. Uhland, J. Schiele, W. Ruehl, R. Finston, P. Day-Lollini, M.L. Goris, “Determinants of the antitumor effect of radiolabeled monoclonal antibodies,” Cancer Res. 50, 4935-4940 (1990).

 

  1. 4.    R.A. Kyle, M.A. Gertz, P.R. Greipp, T.E. Witzig, J.A. Lust, M.Q. Lacy, T.M. Therneau, “Long-term survival (10 years or more) in 30 patients with primary amyloidosis,” Blood, 93(3), 1062-1066 (1999).

 

  1. 5.    M. Dietlein, H. Pels, H. Schulz, O. Staak, P. Borchmann, K. Schomäcker, T. Fischer, W. Eschner, E.P. von Strandmann, H. Schicha, A. Engert, R. Schnell, “Imaging of central nervous system lymphomas with iodine-123 labeled rituximab,” Eur. J. Haematol. 74, 348-352 (2005).

 

  1. 6.    J. Hoffend, W. Mier, J. Schuhmacher, K. Schmidt, A. Dimitrakopoulou-Strauss, L.G. Strauss, M.E.R. Kinscherf, U. Haberkorna, “Gallium-68-DOTA-albumin as a PET blood-pool marker: experimental evaluation in vivo,” Nucl. Med. Biol. 32, 287–292 (2005).

 

  1. 7.    O. Ugur, P.J. Kothari, R.D. Finn, P. Zanzonico, S. Ruan, I. Guenther, H.R. Maecke, S.M. Larson, “Ga-66 labeled somatostatin analogue DOTA-DPhe1-Tyr3-octreotide as a potential agent for positron emission tomography imaging and receptor mediated internal radiotherapy of somatostatin receptor positive tumors,” Nucl. Med. Biol. 29, 147–157 (2002).

 

  1. 8.    M.R. McDevitt, D.Ma,J. Simon, R.K. Frank, D.A. Scheinberg, “Design and synthesis of 225Ac radioimmun opharmaceuticals,”  Applied Radiat. Isot. 57, 841–847 (2002).
  2. 9.    C.J. Smith, H. Gali, G.L. Sieckman, D.L. Hayes, N.K. Owen, D.G. Mazuru, W.A. Volkert, T.J. Hoffman, “Radiochemical investigations of 177Lu-DOTA-8-Aoc-BBN[7-14] NH2: an in vitro/in vivo assessment of the targeting ability of this new radiopharmaceutical for PC-3 human prostate cancer cells,” Nucl. Med. Biol. 30, 101–109 (2003).

 

  1. 10.              L.L. Chappell, E. Dadachova, D.E. Milenic, K. Garmestani, C.Wu, M.W. Brechbiel, “Synthesis, Characterization, and Evaluation of a Novel Bifunctional Chelating Agent for the Lead Isotopes 203Pb and 212Pb,” Nucl. Med. & Biol. 27, 93–100 (2000).

 

11. S. Banerjee, T. Das, S. Chakraborty, G. Samuel, A. Korde, S. Srivastava, M. Venkatesha, M.R.A. Pillai, “177Lu-DOTA-lanreotide: A novel tracer as a targeted agent for tumor therapy,” Nucl. Med. Biol. 31, 753–759 (2004).

 

12. W. Mier, J. Hoffend, S. Kramer, J. Schuhmacher, W.E. Hull, M. Eisenhut,  “Conjugation of DOTA using isolated phenolic active esters: The labeling and biodistribution of albumin as a blood-pool marker,” Bioconjug. Chem. 16, 237–240 (2005).

 

13. U. Pandey, A. Mukherjee, H.D. Sarma, T. Das, M.R.A. Pillai, M. Venkatesh, “Evaluation of 90Y-DTPA and 90Y-DOTA for potential application in intra-vascular radionuclide therapy,” Appl. Rad. Isot. 57, 313-318 (2002).

 

  1. 14.              P. Goethals, M. Coene, G. Slegers, D. Vogelaers, J. Everaert, I. Lemahieu, F. Colardyn, G.R. Heyndrickx, “Production of carrier-free 66Ga and labeling of antimyosin antibody for positron imaging of acute myocardial infarction,” Eur. J. Nucl. Med. 16, 237-240 (1990).

 

  1. 15.              J. Kowalski, M. Henze, J. Schuhmacher, H.R. Macke, M. Hofmann, U. Haberkorn. “Evaluation of positron emission tomography imaging using [68Ga]-DOTA-D Phe(1)-Tyr(3)-Octreotide in comparison to [111In]-DTPAOC SPECT. First results in patients with neuroendocrine tumors,” Mol. Imaging Biol. 5(1), 42-48 (2003).

 

16. U.K. Laemmli, “Cleavage of structural proteins during assembly of the head of the bacteriophage T4,” Nature (London),227, 680–685 (1970).

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