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Microdosimetric analysis of alpha-particle-emitting targeted radiotherapeutics using histological images.

Publication ,  Journal Article
Akabani, G; Kennel, SJ; Zalutsky, MR
Published in: J Nucl Med
May 2003

UNLABELLED: The purpose of this study was to evaluate the therapeutic efficacy and limitations of alpha-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 alpha-particle-emitting (211)At and (213)Bi 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 micro m) and group B consisted of larger tumors (<600 micro m). Probability density functions (pdf) 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 x 10(-3) and 1.37 x 10(-3) Gy g MBq(-1) s(-1) for (211)At and (213)Bi, respectively, and for animals in group B was 3.8 x 10(-4) and 5.6 x 10(-4) Gy g MBq(-1) s(-1) for (211)At and (213)Bi, respectively. The fraction of tumor cells that received a zero absorbed dose for animals in group A was 0.04% for (213)Bi and 0.2% for (211)At and for animals in group B was 25% for (213)Bi and 31% for (211)At. Both (213)Bi- and (211)At-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 alpha-particle endoradiotherapeutic strategies.

Duke Scholars

Published In

J Nucl Med

ISSN

0161-5505

Publication Date

May 2003

Volume

44

Issue

5

Start / End Page

792 / 805

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Radiotherapy Dosage
  • Radiometry
  • Radioisotopes
  • Radioimmunotherapy
  • Nuclear Medicine & Medical Imaging
  • Mice, Inbred BALB C
  • Mice
  • Mammary Neoplasms, Experimental
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Akabani, G., Kennel, S. J., & Zalutsky, M. R. (2003). Microdosimetric analysis of alpha-particle-emitting targeted radiotherapeutics using histological images. J Nucl Med, 44(5), 792–805.
Akabani, Gamal, Stephen J. Kennel, and Michael R. Zalutsky. “Microdosimetric analysis of alpha-particle-emitting targeted radiotherapeutics using histological images.J Nucl Med 44, no. 5 (May 2003): 792–805.
Akabani G, Kennel SJ, Zalutsky MR. Microdosimetric analysis of alpha-particle-emitting targeted radiotherapeutics using histological images. J Nucl Med. 2003 May;44(5):792–805.
Akabani, Gamal, et al. “Microdosimetric analysis of alpha-particle-emitting targeted radiotherapeutics using histological images.J Nucl Med, vol. 44, no. 5, May 2003, pp. 792–805.
Akabani G, Kennel SJ, Zalutsky MR. Microdosimetric analysis of alpha-particle-emitting targeted radiotherapeutics using histological images. J Nucl Med. 2003 May;44(5):792–805.

Published In

J Nucl Med

ISSN

0161-5505

Publication Date

May 2003

Volume

44

Issue

5

Start / End Page

792 / 805

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Radiotherapy Dosage
  • Radiometry
  • Radioisotopes
  • Radioimmunotherapy
  • Nuclear Medicine & Medical Imaging
  • Mice, Inbred BALB C
  • Mice
  • Mammary Neoplasms, Experimental
  • Female