Microdosimetric analysis of α-particle-emitting targeted radiotherapeutics using histological images

Gamal Akabani, Stephen Kennel, Michael R. Zalutsky

Research output: Contribution to journalArticle

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Abstract

The purpose of this study was to evaluate the therapeutic efficacy and limitations of α-particle-emitting radiolabeled compounds by means of 2-dimensional histological images and distribution of activity on a microscopic level. Methods: A microdosimetric approach based on histological images is used to analyze the therapeutic effectiveness of α-particle-emitting 211At and 213Bi conjugated to 201B monoclonal antibody (mAb), which is reactive with murine lung blood vessels for the treatment of EMT-6 lung tumor colonies in nude mice. Autoradiography images were used to define the tissue morphology and activity distribution within lung tissues. Two animal groups were studied: Group A consisted of animals bearing small tumors (<130 μm) and group B consisted of larger tumors (<600 μm). Probability density functions (pdr) described the variability in average absorbed dose and survival probability among normal and tumor target cells and, in turn, were used to assess the survival fraction of tumor and normal tissue. Results: The average absorbed dose to tumor cells per unit cumulated activity concentration for animals in group A was 1.10 × 10-3 and 1.37 × 10-3 Gy g MBq-1 s-1 for 211At and 213Bi, respectively, and for animals in group B was 3.8 × 10-4 and 5.6 × 10-4 Gy g MBq -1 s-1 for 211At and 213Bi, respectively. The fraction of tumor cells that received a zero absorbed dose for animals in group A was 0.04% for 213Bi and 0.2% for 211At and for animals in group B was 25% for 213Bi and 31% for 211At. Both 213Bi- and 211At-labeled 201B mAb were effective therapies for animals with small tumors, where predicted therapeutic effectiveness was consistent with experimental findings; however, they were ineffective for animals with larger tumors. Conclusion: Microdosimetric methods based on knowledge of tissue morphology and activity distribution on a small-scale level can be a useful tool for evaluating a priori the therapeutic efficacy and limitations of targeted α-particle endoradiotherapeutic strategies.

Original languageEnglish (US)
Pages (from-to)792-805
Number of pages14
JournalJournal of Nuclear Medicine
Volume44
Issue number5
StatePublished - May 1 2003

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Neoplasms
Lung
Monoclonal Antibodies
Therapeutics
Autoradiography
Nude Mice
Blood Vessels

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging

Cite this

Microdosimetric analysis of α-particle-emitting targeted radiotherapeutics using histological images. / Akabani, Gamal; Kennel, Stephen; Zalutsky, Michael R.

In: Journal of Nuclear Medicine, Vol. 44, No. 5, 01.05.2003, p. 792-805.

Research output: Contribution to journalArticle

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abstract = "The purpose of this study was to evaluate the therapeutic efficacy and limitations of α-particle-emitting radiolabeled compounds by means of 2-dimensional histological images and distribution of activity on a microscopic level. Methods: A microdosimetric approach based on histological images is used to analyze the therapeutic effectiveness of α-particle-emitting 211At and 213Bi conjugated to 201B monoclonal antibody (mAb), which is reactive with murine lung blood vessels for the treatment of EMT-6 lung tumor colonies in nude mice. Autoradiography images were used to define the tissue morphology and activity distribution within lung tissues. Two animal groups were studied: Group A consisted of animals bearing small tumors (<130 μm) and group B consisted of larger tumors (<600 μm). Probability density functions (pdr) described the variability in average absorbed dose and survival probability among normal and tumor target cells and, in turn, were used to assess the survival fraction of tumor and normal tissue. Results: The average absorbed dose to tumor cells per unit cumulated activity concentration for animals in group A was 1.10 × 10-3 and 1.37 × 10-3 Gy g MBq-1 s-1 for 211At and 213Bi, respectively, and for animals in group B was 3.8 × 10-4 and 5.6 × 10-4 Gy g MBq -1 s-1 for 211At and 213Bi, respectively. The fraction of tumor cells that received a zero absorbed dose for animals in group A was 0.04{\%} for 213Bi and 0.2{\%} for 211At and for animals in group B was 25{\%} for 213Bi and 31{\%} for 211At. Both 213Bi- and 211At-labeled 201B mAb were effective therapies for animals with small tumors, where predicted therapeutic effectiveness was consistent with experimental findings; however, they were ineffective for animals with larger tumors. Conclusion: Microdosimetric methods based on knowledge of tissue morphology and activity distribution on a small-scale level can be a useful tool for evaluating a priori the therapeutic efficacy and limitations of targeted α-particle endoradiotherapeutic strategies.",
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