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Quantitative Whole Body Autoradiographic Microimaging for Pharmaceutical Research

  • Prantika Som
  • Zvi H. Oster

Abstract

Autoradiographic (ARG) microimaging is probably the highest spatial resolution method for imaging the distribution of radiolabeled compounds. This method can be used in sections of whole small animals such as mice, rats and even small monkeys, or in parts of animals, using the new large-block cryomicrotomes. Radiolabeled compounds and their metabolites have been studied in normal animals as well as in animal models of human disease. By sacrificing animals at various time intervals after the injection of the radiocompounds, the dimension of time can be introduced, thus generating data showing the temporo-spatial distribution and biokinetic pathways of compounds. This technique can be used to study the biodistribution of new compounds, the toxicity of substances, and the effects of pharmacological interventions of various active compounds (Som and Sacker, 1992; Ullberg, 1954; Berlin and Ullberg, 1963a; Berlin and Ullberg, 1963b; Cohen and Hood, 1969; Busch, 1977, Cross, 1977a; Cross, 1977b; Som et al., 1983; d’Argy et al., 1984; Yonekura et al., 1985).

Keywords

Prussian Blue Fatty Acid Uptake Placental Transfer Hypertensive Heart Disease Cocaine Uptake 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Appelgren LE (1967): Sites of steroid hormone for median. Autoradiographical studies using labelled precursors. Acta Physiol Scand, 301(Suppl): 1–108.Google Scholar
  2. Bergman K and Tjalve H (1977): Three-step autoradiography of organic and plastic monomers to register total radioactivity, non-volatile metabolites, and non-extractable metabolites. Acta Pharmacol Toxicol 41(Suppl 1): 22–23.Google Scholar
  3. Berlin M and Ullberg (1963a): The fate of Cd109 in the mouse. An autoradiographic study after a single intravenous injection of Cd109Cl2. Arch Environ Hlth 7: 686–693.Google Scholar
  4. Berlin M and Ullberg (1963b): Accumulation and retention of mercury in the mouse. Arch Environ Hlth 6: 589–616.Google Scholar
  5. Busch U (1977): Wholebody autoradiography (WBARG): use for pilot studies of pharmacokinetics in rats. Acta Pharmacol Toxicol 41: 28–29.Google Scholar
  6. Cohen EM and Hood M (1969): Application of low temperature autoradiography to studies of the uptake and metabolism of volatile anaesthetics in mouse. Anesthesiol 30: 306–314.CrossRefGoogle Scholar
  7. Cross SAM (1977a): The localization of metiamide and Cimetidine using autoradiographical techniques. Proc Eur Soc Toxicol 18: 288–290.Google Scholar
  8. Cross SAM (1977b): Localization of histamine H2-receptor antagonist in the gastric mucosa. Histochem J 9: 619–644.CrossRefGoogle Scholar
  9. Cross SAM, Groves AD and Hesselbo T (1974): A quantitative method for measuring radioactivity in tissues sectioned for whole-body autoradiography. Int J Appl Radiat Isot 25: 381–386.CrossRefGoogle Scholar
  10. d’Argy R (1977): Tissue pieces from wholebody sections used for chromatographic separation of metabolites. Acta Pharmacol Toxicol 41 (Suppl. 1): 16–17.Google Scholar
  11. d’Argy R, Ullberg S, Stalacke C-G and Langstorm B (1984): Whole-body autoradiography using 11C with double-tracer applications. Int J Appl Radiat Isot 35: 129–134.CrossRefGoogle Scholar
  12. Denker L (1976): Tissue localization of some teratogens at early and late gestation related to fetal effects. Acta Pharmac 39: 1–131.CrossRefGoogle Scholar
  13. Fand I, McNally WP, Koul O, Yonekur Y, Som P, Brill AB and Deutch DG (1988): Whole-body autoradiographic localization of (3H) Phenylcycline and its metabolites in mice. Toxicol Appl Pharmacol 93: 421–432.CrossRefGoogle Scholar
  14. Gooche C, Rasband W and Sokoloff L (1980): Computerized densitometry and color coding of (14C) deoxyglucose autoradiography. Ann Neurol 7: 359–370.CrossRefGoogle Scholar
  15. Irons RD and Gross EA (1981): Standardization and calibration of wholebody autoradiography for routine semiquantitatives analysis of the distribution of 14C-labeled compounds in animal tissues. Toxicol Appl Pharmacol 59: 250–256.CrossRefGoogle Scholar
  16. Kubota K, Som P, Oster ZH, Brill AB, Goodman MM, Knapp FF Jr, Atkins HL and Sole MJ (1988): Detection of cardiomyopathy in an animal mode using quantitative autoradiography. J. Nucl Med 29: 1697–1703.Google Scholar
  17. Kuhl DE, Barrio JR, Huang S-C, Selin C, Acerkmann RF, Lear JL, Wu JL, Lin TH and Phelps PE (1982): Quantifying local cerebral blood flow by N-isopropyl-p-[123I]iodoamphetamine (IMP) tomography. J. Nucl Med 23: 196–203.Google Scholar
  18. Masukoa DT and Pfeiffer E (1977): An in-vivo brain autoradiographic technique and a digital microdensitometer for the quantitation of autoradiograms. Acta Pharmacol Toxicol (Suppl. 1) 41: 54–55.Google Scholar
  19. Oster ZH, Som P, Brill AB, Sacker DF and Atkins HL (1982): Enhancement of radiopharmaceutical excretion by chemical interventions In: Proceeding of the 3rd World Congress of Nuclear Medicine and Biology, Vol 4, Raynaud C, ed. Paris: Pergamon Press.Google Scholar
  20. Oster ZH, Som P, Rhodes BA, Wong CTC, Cabahug C, Sacker, DF, Wang G-J and Meinken GE (1992): A one-step Kit for 99mTc-labeling of non-specific immunoglobulin (HIG): Imaging of inflammation and tumor J Nucl Med 33:1028.Google Scholar
  21. Oster ZH, Som P, Srivastava SC, Fairchild RG, Meinken GE, Tillman DY, Sacker DF, Richards P, Atkins HL, Brill AB, Knapp FF Jr and Butler TA (1985): The development and in vivo behavior of tin-containing radio-pharmaceuticals. II. Autographic and scintigraphic studies in normal animals and in animal models of bone bone disease. Int J Nucl Med Biol 12: 175–184.CrossRefGoogle Scholar
  22. Sokoloff L, Revich M, Kennedy C, Des Rosier MH, Patlak CS, Pettigrew KD, Sakurado O and Shinohara M (1977): The (14C) deoxyglucose method for measurement of local cerebral glucose utilization: Theory, procedure and normal values in the conscious and anaesthetized albino rats. J Neurochem 28: 897–916.CrossRefGoogle Scholar
  23. Som P, Oster ZH, Yamamoto K, Meinken GE, Srivastava SC, Yonekura Y, Ebner SA, Atkins HL, Brill AB, Fawwaz RA, Alderson PO, Coffey J, Carlton E and Hubner KF (1985): Some factors affecting the cerebral and extracerebral accumulation of N-isopropyl-p-iodo-amphetamine (IAMP). Int J Nucl Med Biol 12: 185–196.CrossRefGoogle Scholar
  24. Som P, Oster ZH, Volkow ND, Sacker DF and Weber DA (1989): Studies on wholebody distribution and kinetics of cocaine. J Nucl Med 30: 831.Google Scholar
  25. Som P, Oster ZH, Volkow ND, Sacker DF and Weber DA (1990): Organ variations in cocaine receptors. J Nucl Med 31: 886.Google Scholar
  26. Som P, Oster ZH, Wang G-J, Volkow ND and Sacker DF (1992): Wholebody autoradiographic microimaging studies of the spatial and temporal distribution of cocaine. Synapse, in press.Google Scholar
  27. Som P and Sacker DF (1992): Whole-Body autoradiographic microimaging: Applications in radiopharmaceutical and drug research. In: Using Autoradiography and Correlative Imaging in vitro and in vivo. Stumpf W and Solomon H, eds. San Diego: Academic Press, in press.Google Scholar
  28. Som P, Yonekura Y, Oster ZH, Meyer MA, Pelletteri ML, MacGregor RR, Russell JA, Wolf AP, Fand I, McNally WP and Brill AB (1983): Quantitative autoradiography with radiopharmaceuticles. Part II: Applications in radiopharmaceutical research. J Nucl Med 24: 238–244.Google Scholar
  29. Ullberg S, Kristofferson H, Flodh H, and Hanngren Å (1967): Placental passage and fetal accumulation of labelled vitamin B12 in the mouse. Arch Int Pharmacodyn Ther 167: 431–449.Google Scholar
  30. Ullberg S, Sorbo B, and Clemedson C-J (1961): Distribution of radioactive iron in pregnant mice studied in whole-body autoradiography. Acta Radiol 55: 145–155.CrossRefGoogle Scholar
  31. Ullberg S and Dencker L (1977): Localization in fetal tissues. Acta Pharmacol Toxical 41 (Suppl. 1) 170–171.Google Scholar
  32. Ullberg S (1954): Studies on the distribution and fate of 35S-labelled benzyl penicillin in the body. Acta Radiol, Suppl. 118: 1–10.Google Scholar
  33. Ullberg S (1977): Conference on Autoradiography in Pharmacology and Toxicology. In: Acta Pharmacol Toxicol 41, suppl, 1. Ullberg S, Applegren LE, Dencker L, Hammarstrom L, Hansson E and Tjalve H, eds. Copenhagen: Munksgaard Publ.Google Scholar
  34. van der Kleijn K, Rijntjes NVM, Vree TB, Schobben F, Westenberg H, Jonkman J, Knop HJ and van Geyn H (1977): Similarities and differences in the kinetics of distribution and of placental transfer of anti-epileptic drugs of extremely varying physico-chemical properties. Acta Pharmacol Toxicol 41 (Suppl. 1): 168–169.Google Scholar
  35. Winchell HS, Baldwin RM and Lin TH (1980): Development of I-123 labeled amines for brain studies: localization of I-123 iodophenylalkyl amines in rat brain. J Nucl Med 21: 940–946.Google Scholar
  36. Yonekura Y, Brill AB, Som P, Yamamoto K, Srivastava SC, Iwi J, Elmaleh DR, Livni E, Strauss HW, Goodman MM and Knapp FF Jr (1985): Quantitative autoradiographic measurement of regional myocardial substrate utilization in hypertensive rats. Science 227: 1494–1446.CrossRefGoogle Scholar
  37. Yonekura Y. Brill AB, Som P, Bennett GW and Fand I (1983): Quantitative autoradiography with radiopharmaceuticals. Part I: Digital film analysis system by videodensitometry. J Nucl Med 24: 231–237.Google Scholar
  38. Zamora PO, Pant KD, Shah VO, Sass KS, Newell KD, Shao HS, Oster ZH and Som P (1988): Anti-Colon/ovarian tumor antigen: Localization of colon cancer Xenograft in athymic rats. Int J Nucl Med Biol 15: 261–270.Google Scholar

Copyright information

© Birkhäuser Boston 1993

Authors and Affiliations

  • Prantika Som
    • 1
  • Zvi H. Oster
    • 2
  1. 1.Medical DepartmentBrookhaven National LaboratoryUSA
  2. 2.Department of RadiologyState University of New York at Stony BrookUSA

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