Comparative cellular catabolism and retention of astatine-, bismuth-, and lead-radiolabeled internalizing monoclonal antibody

Z. Yao, K. Garmestani, K. J. Wong, L. S. Park, E. Dadachova, A. Yordanov, T. A. Waldmann, W. C. Eckelman, C. H. Paik, J. A. Carrasquillo

Research output: Contribution to journalArticle

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Abstract

Monoclonal antibodies (mAbs) labeled with α-emitting radionuclides such as 211At, 212Bi, 213Bi, and 212Pb (which decays by β-emission to its α-emitting daughter, 212Bi) are being evaluated for their potential applications for cancer therapy. The fate of these radionuclides after cells are targeted with mAbs is important in terms of dosimetry and tumor detection. Methods: In this study, we attached various radionuclides that result in α-emissions to T101, a rapidly internalizing anti-CD5 mAb. We then evaluated the catabolism and cellular retention and compared them with those of 125I- and 111In-labeled T101. T101 was labeled with 211At, 125I, 205,6Bi, 111In, and 203Pb. CD5 antigen-positive cells, peripheral blood mononuclear cells (PBMNC), and MOLT-4 leukemia cells were used. The labeled T101 was incubated with the cells for 1 h at 4°C for surface labeling. Unbound activity was removed and 1 mL medium added, The cells were then incubated at 37°C for 0, 1, 2, 4, 8, and 24 h. The activity on the cell surface that internalized and the activity on the cell surface remaining in the supernatant were determined. The protein in the supernatant was further precipitated by methanol for determining protein-bound and non-protein-bound radioactivity, Sites of internal cellular localization of radioactivity were determined by Percoll gradient centrifugation. Results: All radiolabeled antibodies bound to the cells were internalized rapidly. After internalization, 205,6Bi, 203Pb, and 111In radiolabels were retained in the cell, with little decrease of cell-associated radioactivity. However, 211At and 125I were released from cells rapidly (211At<125I) and most of the radioactivity in the supernatant was in a non-protein-bound form. Intracellular distribution of radioactivity revealed a transit of the radiolabel from the cell surface to the lysosome. The catabolism patterns of MOLT-4 cells and PBMNC were similar, Conclusion: 211At catabolism and release from cells were somewhat similar to that of 125I, whereas 205,6Bi and 203Pb showed prolonged cell retention similar to that of 111In. These catabolism differences may be important in the selection of α-radionuclides for radioimmunotherapy.

Original languageEnglish (US)
Pages (from-to)1538-1544
Number of pages7
JournalJournal of Nuclear Medicine
Volume42
Issue number10
StatePublished - 2001
Externally publishedYes

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Astatine
Monoclonal Antibodies
Radioactivity
Radioisotopes
bismuth lead
Blood Cells
CD5 Antigens
Radioimmunotherapy

Keywords

  • α-emitter
  • Cellular retention
  • Internalization
  • Monoclonal antibody

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Yao, Z., Garmestani, K., Wong, K. J., Park, L. S., Dadachova, E., Yordanov, A., ... Carrasquillo, J. A. (2001). Comparative cellular catabolism and retention of astatine-, bismuth-, and lead-radiolabeled internalizing monoclonal antibody. Journal of Nuclear Medicine, 42(10), 1538-1544.

Comparative cellular catabolism and retention of astatine-, bismuth-, and lead-radiolabeled internalizing monoclonal antibody. / Yao, Z.; Garmestani, K.; Wong, K. J.; Park, L. S.; Dadachova, E.; Yordanov, A.; Waldmann, T. A.; Eckelman, W. C.; Paik, C. H.; Carrasquillo, J. A.

In: Journal of Nuclear Medicine, Vol. 42, No. 10, 2001, p. 1538-1544.

Research output: Contribution to journalArticle

Yao, Z, Garmestani, K, Wong, KJ, Park, LS, Dadachova, E, Yordanov, A, Waldmann, TA, Eckelman, WC, Paik, CH & Carrasquillo, JA 2001, 'Comparative cellular catabolism and retention of astatine-, bismuth-, and lead-radiolabeled internalizing monoclonal antibody', Journal of Nuclear Medicine, vol. 42, no. 10, pp. 1538-1544.
Yao, Z. ; Garmestani, K. ; Wong, K. J. ; Park, L. S. ; Dadachova, E. ; Yordanov, A. ; Waldmann, T. A. ; Eckelman, W. C. ; Paik, C. H. ; Carrasquillo, J. A. / Comparative cellular catabolism and retention of astatine-, bismuth-, and lead-radiolabeled internalizing monoclonal antibody. In: Journal of Nuclear Medicine. 2001 ; Vol. 42, No. 10. pp. 1538-1544.
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abstract = "Monoclonal antibodies (mAbs) labeled with α-emitting radionuclides such as 211At, 212Bi, 213Bi, and 212Pb (which decays by β-emission to its α-emitting daughter, 212Bi) are being evaluated for their potential applications for cancer therapy. The fate of these radionuclides after cells are targeted with mAbs is important in terms of dosimetry and tumor detection. Methods: In this study, we attached various radionuclides that result in α-emissions to T101, a rapidly internalizing anti-CD5 mAb. We then evaluated the catabolism and cellular retention and compared them with those of 125I- and 111In-labeled T101. T101 was labeled with 211At, 125I, 205,6Bi, 111In, and 203Pb. CD5 antigen-positive cells, peripheral blood mononuclear cells (PBMNC), and MOLT-4 leukemia cells were used. The labeled T101 was incubated with the cells for 1 h at 4°C for surface labeling. Unbound activity was removed and 1 mL medium added, The cells were then incubated at 37°C for 0, 1, 2, 4, 8, and 24 h. The activity on the cell surface that internalized and the activity on the cell surface remaining in the supernatant were determined. The protein in the supernatant was further precipitated by methanol for determining protein-bound and non-protein-bound radioactivity, Sites of internal cellular localization of radioactivity were determined by Percoll gradient centrifugation. Results: All radiolabeled antibodies bound to the cells were internalized rapidly. After internalization, 205,6Bi, 203Pb, and 111In radiolabels were retained in the cell, with little decrease of cell-associated radioactivity. However, 211At and 125I were released from cells rapidly (211At<125I) and most of the radioactivity in the supernatant was in a non-protein-bound form. Intracellular distribution of radioactivity revealed a transit of the radiolabel from the cell surface to the lysosome. The catabolism patterns of MOLT-4 cells and PBMNC were similar, Conclusion: 211At catabolism and release from cells were somewhat similar to that of 125I, whereas 205,6Bi and 203Pb showed prolonged cell retention similar to that of 111In. These catabolism differences may be important in the selection of α-radionuclides for radioimmunotherapy.",
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AU - Garmestani, K.

AU - Wong, K. J.

AU - Park, L. S.

AU - Dadachova, E.

AU - Yordanov, A.

AU - Waldmann, T. A.

AU - Eckelman, W. C.

AU - Paik, C. H.

AU - Carrasquillo, J. A.

PY - 2001

Y1 - 2001

N2 - Monoclonal antibodies (mAbs) labeled with α-emitting radionuclides such as 211At, 212Bi, 213Bi, and 212Pb (which decays by β-emission to its α-emitting daughter, 212Bi) are being evaluated for their potential applications for cancer therapy. The fate of these radionuclides after cells are targeted with mAbs is important in terms of dosimetry and tumor detection. Methods: In this study, we attached various radionuclides that result in α-emissions to T101, a rapidly internalizing anti-CD5 mAb. We then evaluated the catabolism and cellular retention and compared them with those of 125I- and 111In-labeled T101. T101 was labeled with 211At, 125I, 205,6Bi, 111In, and 203Pb. CD5 antigen-positive cells, peripheral blood mononuclear cells (PBMNC), and MOLT-4 leukemia cells were used. The labeled T101 was incubated with the cells for 1 h at 4°C for surface labeling. Unbound activity was removed and 1 mL medium added, The cells were then incubated at 37°C for 0, 1, 2, 4, 8, and 24 h. The activity on the cell surface that internalized and the activity on the cell surface remaining in the supernatant were determined. The protein in the supernatant was further precipitated by methanol for determining protein-bound and non-protein-bound radioactivity, Sites of internal cellular localization of radioactivity were determined by Percoll gradient centrifugation. Results: All radiolabeled antibodies bound to the cells were internalized rapidly. After internalization, 205,6Bi, 203Pb, and 111In radiolabels were retained in the cell, with little decrease of cell-associated radioactivity. However, 211At and 125I were released from cells rapidly (211At<125I) and most of the radioactivity in the supernatant was in a non-protein-bound form. Intracellular distribution of radioactivity revealed a transit of the radiolabel from the cell surface to the lysosome. The catabolism patterns of MOLT-4 cells and PBMNC were similar, Conclusion: 211At catabolism and release from cells were somewhat similar to that of 125I, whereas 205,6Bi and 203Pb showed prolonged cell retention similar to that of 111In. These catabolism differences may be important in the selection of α-radionuclides for radioimmunotherapy.

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KW - α-emitter

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