Literature DB >> 16741316

Log normal distribution of cellular uptake of radioactivity: implications for biologic responses to radiopharmaceuticals.

Prasad V S V Neti1, Roger W Howell.   

Abstract

UNLABELLED: It is widely recognized that radiopharmaceuticals are generally distributed nonuniformly in tissues. Such nonuniformities are observed over the entire range of spatial levels, ranging from organ to subcellular levels. The implications of nonuniform distributions of radioactivity for dosimetry, and ultimately for the biologic response of tissues containing radioactivity, have been investigated extensively. However, there is a paucity of experimental data on the distribution of cellular activity within a population of cells. In the present study, the distribution of activity per cell is experimentally determined and its implications for predicting biologic response are examined.
METHODS: Chinese hamster V79 cells were exposed to different concentrations of (210)Po-citrate. The radiolabeled cells were washed, seeded into culture dishes or glass slides, covered with photographic emulsion, and stored in an opaque container. Subsequently, the emulsion was developed, thereby resulting in observable alpha-particle tracks that were scored.
RESULTS: The distribution of activity per cell was found to be well described by a log normal distribution function. Theoretic modeling of cell survival as a function of mean activity per cell showed that survival curves differed substantially when the activity per cell was log normally distributed versus when it was assumed conventionally that every cell in the population contained the mean activity.
CONCLUSION: The present study provides experimental evidence of log normal cellular uptake of radioactivity. Theoretic calculations show that a log normal distribution of cellular activity can have a substantial impact on modeling the biologic response of cell populations.

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Year:  2006        PMID: 16741316      PMCID: PMC2631404     

Source DB:  PubMed          Journal:  J Nucl Med        ISSN: 0161-5505            Impact factor:   10.057


  14 in total

1.  Quantitative autoradiography for the study of radiopharmaceutical uptake and dose heterogeneity.

Authors:  P L Roberson
Journal:  J Nucl Med       Date:  1992-10       Impact factor: 10.057

2.  A quantitative autoradiographic study of the heterogeneous activity distribution of different indium-111-labeled radiopharmaceuticals in rat tissues.

Authors:  B A Jönsson; S E Strand; B S Larsson
Journal:  J Nucl Med       Date:  1992-10       Impact factor: 10.057

3.  Log normal distribution of cellular uptake of radioactivity: implications for biologic responses to radiopharmaceuticals.

Authors:  Prasad V S V Neti; Roger W Howell
Journal:  J Nucl Med       Date:  2006-06       Impact factor: 10.057

4.  Statistical modelling of Poisson/log normal data.

Authors:  Guthrie Miller
Journal:  Radiat Prot Dosimetry       Date:  2007-01-12       Impact factor: 0.972

5.  Search for 1/f fluctuations in alpha decay of 210Po.

Authors: 
Journal:  Phys Rev A Gen Phys       Date:  1989-05-15

6.  Autoradiographic studies of the distribution of polonium-210 in mice after a single intravenous injection.

Authors:  R Söremark; V R Hunt
Journal:  Int J Radiat Biol Relat Stud Phys Chem Med       Date:  1966

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

Authors:  Gamal Akabani; Stephen J Kennel; Michael R Zalutsky
Journal:  J Nucl Med       Date:  2003-05       Impact factor: 10.057

8.  Alpha-particle emitting atomic generator (Actinium-225)-labeled trastuzumab (herceptin) targeting of breast cancer spheroids: efficacy versus HER2/neu expression.

Authors:  Ase M Ballangrud; Wei-Hong Yang; Stig Palm; Richard Enmon; Paul E Borchardt; Virginia A Pellegrini; Michael R McDevitt; David A Scheinberg; George Sgouros
Journal:  Clin Cancer Res       Date:  2004-07-01       Impact factor: 12.531

9.  Internal dosimetry using data derived from autoradiographs.

Authors:  J L Humm; R M Macklis; K Bump; L M Cobb; L M Chin
Journal:  J Nucl Med       Date:  1993-10       Impact factor: 10.057

10.  Concomitant quantification of targeted drug delivery and biological response in individual cells.

Authors:  Massimo Pinto; Roger W Howell
Journal:  Biotechniques       Date:  2007-07       Impact factor: 1.993

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  24 in total

1.  A method to predict response of cell populations to cocktails of chemotherapeutics and radiopharmaceuticals: validation with daunomycin, doxorubicin, and the alpha particle emitter (210)Po.

Authors:  John M Akudugu; Roger W Howell
Journal:  Nucl Med Biol       Date:  2012-04-14       Impact factor: 2.408

2.  Log normal distribution of cellular uptake of radioactivity: implications for biologic responses to radiopharmaceuticals.

Authors:  Prasad V S V Neti; Roger W Howell
Journal:  J Nucl Med       Date:  2006-06       Impact factor: 10.057

3.  Employing a Mechanistic Model for the MAPK Pathway to Examine the Impact of Cellular all or None Behavior on Overall Tissue Response.

Authors:  Nicholas S Luke; Michael J Devito; Christopher J Portier; Hisham A El-Masri
Journal:  Dose Response       Date:  2010-01-29       Impact factor: 2.658

Review 4.  Challenges and progress in predicting biological responses to incorporated radioactivity.

Authors:  R W Howell; P V S V Neti; M Pinto; B I Gerashchenko; V R Narra; E I Azzam
Journal:  Radiat Prot Dosimetry       Date:  2007-02-06       Impact factor: 0.972

5.  Biological response to nonuniform distributions of (210)Po in multicellular clusters.

Authors:  Prasad V S V Neti; Roger W Howell
Journal:  Radiat Res       Date:  2007-09       Impact factor: 2.841

6.  A model of cellular dosimetry for macroscopic tumors in radiopharmaceutical therapy.

Authors:  Robert F Hobbs; Sébastien Baechler; De-Xue Fu; Caroline Esaias; Martin G Pomper; Richard F Ambinder; George Sgouros
Journal:  Med Phys       Date:  2011-06       Impact factor: 4.071

7.  Lognormal distribution of cellular uptake of radioactivity: statistical analysis of alpha-particle track autoradiography.

Authors:  Prasad V S V Neti; Roger W Howell
Journal:  J Nucl Med       Date:  2008-05-15       Impact factor: 10.057

Review 8.  Treatment of Radiation Injury.

Authors:  Sadanori Akita
Journal:  Adv Wound Care (New Rochelle)       Date:  2014-01-01       Impact factor: 4.730

9.  Survival of tumor and normal cells upon targeting with electron-emitting radionuclides.

Authors:  Didier Rajon; Wesley E Bolch; Roger W Howell
Journal:  Med Phys       Date:  2013-01       Impact factor: 4.071

10.  MIRD Pamphlet No. 22 (abridged): radiobiology and dosimetry of alpha-particle emitters for targeted radionuclide therapy.

Authors:  George Sgouros; John C Roeske; Michael R McDevitt; Stig Palm; Barry J Allen; Darrell R Fisher; A Bertrand Brill; Hong Song; Roger W Howell; Gamal Akabani; Wesley E Bolch; A Bertrand Brill; Darrell R Fisher; Roger W Howell; Ruby F Meredith; George Sgouros; Barry W Wessels; Pat B Zanzonico
Journal:  J Nucl Med       Date:  2010-01-15       Impact factor: 10.057

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