Skip to main content
SpringerLink
Log in

Experimental Models and Evaluation of Animal Data for Renal Radiodiagnostic Agents

  • Chapter
Animal Models in Radiotracer Design

Abstract

After a new gamma-emitting radiodiagnostic agent is synthesized and its chemical structure defined, serial camera imaging following administration to experimental animals can quickly determine its major organ localization. Blood and plasma disappearance curves and urinary excretion at different time intervals are also measured. For renal agents, with negligible extrarenal concentration or excretion, a double exponential analysis of the plasma disappearance curve may be used to quantitate renal clearance, in dogs (Blaufox et al., 1963) or even in small animals like the rat (Blaufox et al., 1970). If a new agent appears promising for eventual human use, more detailed concentration values are required for various organs at different time intervals. These are generally obtained by direct tissue radioassay following the sacrifice of a series of animals. It is frequently rewarding to compare (by dual channel pulse height analysis) the distribution of a new agent with that of an older one with similar organ localization, simultaneously injected and labeled with a radionuclide of different gamma energy. These tissue concentration data from animals are essential to calculate preliminary radiation dose estimates, before administration to humans is considered.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adolph, E. F. (1949). Quantitative relations in the physiological constitution of mammals. Science 109:579–585.

    Article  PubMed  CAS  Google Scholar 

  • Andrus, S. B., Gershoff, S. N., Faragalla, F. F., and Prier, E. L. (1960). Production of calcium oxalate renal calculi in vitamin B6-deficient rats. Lab. Invest. 9:7–27.

    PubMed  CAS  Google Scholar 

  • Arnold, R. W., Subramanian, G., McAfee, J. G., Blair, R. J., and Thomas, F. D. (1975). Comparison of 99mTc complexes for renal imaging. J. Nucl. Med. 16:357–367.

    PubMed  CAS  Google Scholar 

  • Berliner, R. W., Kennedy, T. J., and Hilton, J. G. (1950). Effect of maleic acid on renal function. Proc. Soc. Exp. Biol. Med. 75:791–794.

    PubMed  CAS  Google Scholar 

  • Black, J., Calesnick, B., Williams, D., and Weinstein, M. J. (1964). Pharmacology of gentamicin, a new broad-spectrum antibiotic. Antimicrobiol. Agents Chemother. 1963:138–147.

    Google Scholar 

  • Blaufox, M. D., Orvis, A. L., and Owen, C. A., Jr. (1963). Compartmental analysis of the radiorenogram and distribution of Hippuran I131 in dogs. Am. J. Physiol. 204:1059–1064.

    PubMed  CAS  Google Scholar 

  • Blaufox, M. D., and Cohen, A. (1970). Single-injection clearances of iothalamate—131I in the rat. Am. J. Physiol. 218:542–544.

    PubMed  CAS  Google Scholar 

  • Blau, M. (1975). Radiation dosimetry of 131I-19-iodocholesterol: The pitfalls of using tissue concentration data. J. Nucl. Med. 16:247–248.

    PubMed  CAS  Google Scholar 

  • Bolton, W. K., Benton, F. R., Maclay, J. G., and Sturgill, B. C. (1976). Spontaneous glomerular sclerosis in aging Sprague-Dawley rats. Am. J. Pathol. 85:277–300.

    PubMed  CAS  Google Scholar 

  • Brewer, N. R. (1977). Some oddities of the rabbit kidney. Synapse (American Society of Laboratory Animal Practioners) 10:19–22.

    Google Scholar 

  • Bricker, N. S., Dewey, R. R., and Lubowitz, H. (1958). Studies in experimental pyelonephritis: Simultaneous and serial investigation of a pyelonephritic and intact kidney in the same animal. Clin. Res. 6:292–293.

    Google Scholar 

  • Cohen, L., Lapkin, R., and Kaloyanides, G. J. (1975). Effect of gentamicin on renal function in the rat. J. Pharmacol. Exp. Ther. 193:264–273.

    PubMed  CAS  Google Scholar 

  • Dahl, L. K., and Schackow, E. (1964). Effects of chronic excess salt ingestion: Experimental hypertension in the rat. Can. Med. Assoc. J. 90:155–160.

    PubMed  CAS  Google Scholar 

  • Dedrick, R. L., Bischoff, K. B., and Zaharko, D. S. (1970). Interspecies correlation of plasma concentration history of Methotrexate (NSC-740). Cancer Chem. Rep. Part 1, 54:95–101.

    CAS  Google Scholar 

  • Dicker, S. E., and Heller, H. (1935). Relationship between glomerular filtration rate and urine flow in the rabbit. Science 112:340–341.

    Article  Google Scholar 

  • Dobyan, D. C., Levi, J., Jacobs, C., Kosek, J., and Weiner, M. W. (1980). Mechanisms of cis-platinum nephrotoxicity II morphologic observations. J. Pharmacol. Exp. Ther. 213:551–556.

    PubMed  CAS  Google Scholar 

  • Elgee, N. J., and Williams, R. H. (1955). Specificity of insulin degradation reaction. Diabetes 4:87–91.

    PubMed  CAS  Google Scholar 

  • Freireich, E. J., Gehan, E. A., Rall, D. P., Schmidt, L. H., and Skipper, H. E. (1966). Quantitative comparison of toxicity of anticaner agents in mouse, rat, hamster, dog, monkey and man. Cancer Chem. Rep. 50:219–244.

    CAS  Google Scholar 

  • Frenk, S., Antonowicz, I., Craig, J. M., and Metcoff, J. (1955). Experimental nephrotic syndrome induced in rats by aminonucleoside renal lesions and body electrolyte composition. Proc. Soc. Exp. Biol. Med. 89:424–427.

    PubMed  CAS  Google Scholar 

  • Giacomini, K. M., Roberts, S. M., and Levy, G. (1981). Evaluation of methods for producing renal dysfunction in rats. J. Pharmaceut. Sci. 70:117–121.

    Article  CAS  Google Scholar 

  • Hodson, C. J., Maling, T. M. J., McManamon, P. J., and Lewis, M. G. (1975). The pathogenesis of reflux nephropathy (chronic atrophic pyelonephritis). Br. J. Radiol. (Suppl.) 13:1–26.

    Google Scholar 

  • Hoyer, J. R., Maure, S. M., and Michael, A. F. (1975). Unilateral renal disease in the rat. I. Clinical morphologic and glomerular mesangial junctural fractures of the experimental model produced by renal perfusion with aminonucleoside. J. Lab. Clin. Med. 85:756–768.

    PubMed  CAS  Google Scholar 

  • Jones, S. E., Lilien, O. M., and Rogers, L. (1963). Renal pelvic pressure and its relation to renal nemodynamics. J. Urol. 90:357–360.

    PubMed  CAS  Google Scholar 

  • Kenney, J. M., Marinelli, L. D., and Woodard, H. Q. (1941). Tracer studies with radioactive phosphorus in malignant neoplastic disease. Radiology 37:683–690.

    CAS  Google Scholar 

  • Kirschner, A. S., Ice, R. D., and Beierwaltes, W. H. (1975). The Author’s Reply. J. Nucl. Med. 16:248–249.

    CAS  Google Scholar 

  • Korobkin, M., and Shanser, J. D. (1974). Controlled unilateral renal artery hypotension in dogs. Radiology 111:457–460.

    PubMed  CAS  Google Scholar 

  • Lannigan, R. (1963). The production of chronic renal disease in rats by a single intravenous injection of aminonucleoside of puromycin and the effect of low dosage hydrocortisone. Br. J. Exp. Pathol. 44:326–333.

    PubMed  CAS  Google Scholar 

  • Lewis, E. J., and Couser, W. G. (1971). The immunologic basis of human renal disease. Ped. Clin. N. Am. 18:467–507.

    CAS  Google Scholar 

  • Long, R. G., McAfee, J. G., and Winkelman, J. (1963). Evaluation of radioactive compounds for the external detection of cerebral tumors. Cancer Res. 23:98–108.

    Google Scholar 

  • McAfee, J. G., and Subramanian, G. (1981). Interpretation of Interspecies Differences in the Biodistribution of Radioactive Agents. Third International Radiopharmaceutical Dosimetry Symposium, Oak Ridge, Tennessee. Oct. 7–10, 1980. Watson, E. E., Schlafke-Stelson, A. T., Coffey, J. L., and Cloutier, R. J., eds. Rockville, MD: Bureau of Radiological Health, 292–306.

    Google Scholar 

  • McAfee, J. G., Grossman, Z. D., Gagne, G., Zens, A. L., Subramanian, G., Thomas, F. D., Fernandes, P., and Roskopf, M. (1981). Comparison of renal extraction efficiency of radioactive agents in the normal dog. J. Nucl. Med. 22:333–338.

    PubMed  CAS  Google Scholar 

  • McGiff, J. G., and Quilley, C. P. (1981). The rat with spontaneous genetic hypertension is not a suitable model of human essential hypertension. Circ. Res. 48:455–464.

    PubMed  CAS  Google Scholar 

  • McMahon, T. (1973). Size and shape in biology. Science 179:1201–1204.

    Article  PubMed  CAS  Google Scholar 

  • Mellet, L. B. (1969). Comparative drug metabolism. In Progress in Drug Research, Vol. 13, Jucker, E., ed. Basel: Birkhauser Verlag, pp. 138–169.

    Google Scholar 

  • Miller, T. E., and Robinson, K. B. (1973). Experimental pyelonephritis: A new method for inducing pyelonephritis in the rat. J. Infect. Dis. 127:307–310.

    Article  PubMed  CAS  Google Scholar 

  • Oakamoto, K., and Aoki, K. (1963). Development of a strain of spontaneously hypertensive rats. Jap. Circ. J. 27:282–293.

    Article  Google Scholar 

  • Oldendorf, W. H. (1974). Expression of tissue isotope distribution. J. Nucl. Med. 15:725–726.

    PubMed  CAS  Google Scholar 

  • Potokar, M., and Schmidt-Dunker, M. (1978). The inhibitory effect of new diphosphonic acids on aortic and kidney calcification in vivo. Atherosclerosis 30:313–320.

    Article  PubMed  CAS  Google Scholar 

  • Ransley, P. G., and Risdon, R. A. (1978). Reflux and renal scarring. Br. J. Radiol. (Suppl.) 14:1–35.

    Google Scholar 

  • Rennick, B. R., Kandel, A., and Peters, L. (1956). Inhibition of the renal tubular excretion of tetraethylammonium and N’-methylnicotinamide by basic cyanine dyes. J. Pharmacol. Exp. Ther. 118:204–219.

    PubMed  CAS  Google Scholar 

  • Rosenberg, L. E., and Segal, S. (1964). Maleic acid-induced inhibition of amino acid transport in rat kidney. Biochem. J. 92:345–352.

    PubMed  CAS  Google Scholar 

  • Ryan, G. B., and Karnovsky, M. J. (1975). An ultrastructural study of the mechanisms of proteinuria in aminonucleoside nephrosis. Kidney Intern. 8:219–232.

    Article  CAS  Google Scholar 

  • Salant, D. J., Darby, C., and Couser, W. G. (1980). Experimental membranous glomerulonephritis in rats: Quantitative studies of glomerular immune deposit formation in isolated glomeruli and whole animals. J. Clin. Inv. 66:71–81.

    Article  CAS  Google Scholar 

  • Seiler, M. W., Rennke, H. G., Venkatachalam, M. A., and Cotran, R. S. (1977). Pathogenesis of polycation-induced alterations (“fusion”) of glomerular epithelium. Lab. Invest. 36:48–61.

    PubMed  CAS  Google Scholar 

  • Sharon, Z., Schwartz, M. M., and Lewis, E. J. (1977). The glomerular localization and transport of aggregated protamine-heparin complexes. Lab. Invest. 37:43–52.

    PubMed  CAS  Google Scholar 

  • Sherwood, T., Swales, J. D., and Tange, J. D. (1971). Experimental renal papillary necrosis: Progressive changes on intravenous urography. Invest. Radiol. 6:239–244.

    Article  PubMed  CAS  Google Scholar 

  • Spector, W. S., ed. (1956). Handbook of Biological Data, Philadelphia: W. B. Saunders.

    Google Scholar 

  • Stara, J. F., Nelson, N. S., Delia Rose, R. J., and Bustad, L. K. (1971). Comparative metabolism of radionuclides in mammals: A review. Health Phys. 20:113–137.

    Article  PubMed  CAS  Google Scholar 

  • Williams, P. D., Holohan, P. D., and Ross, C. R. (1981). Gentamicin nephrotoxicity. I. Acute biochemical correlates in rats. Toxicol. Appl. Pharmacol. 61:234–242.

    Article  PubMed  CAS  Google Scholar 

  • Woodard, H. Q., Biggler, R. E., Freed, B., and Russ, G. (1975). Expression of tissue isotope distribution. J. Nucl. Med. 16:958–959.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. John G. McAfee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gopal Subramanian
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Chemistry Department, Brookhaven National Laboratory, 11973, Upton, NY, USA

    Richard M. Lambrecht

  2. Section of Radiopharmaceutical Chemistry, George Washington University Medical Center, 20037, Washington, DC, USA

    William C. Eckelman

Rights and permissions

Reprints and permissions

Copyright information

© 1983 Springer-Verlag New York Inc.

About this chapter

Cite this chapter

McAfee, J.G., Subramanian, G. (1983). Experimental Models and Evaluation of Animal Data for Renal Radiodiagnostic Agents. In: Lambrecht, R.M., Eckelman, W.C. (eds) Animal Models in Radiotracer Design. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-5596-3_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4612-5596-3_7

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-5598-7

  • Online ISBN: 978-1-4612-5596-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation