Cancer Chemotherapy and Pharmacology

, Volume 25, Issue 6, pp 389–394 | Cite as

Platinum distribution inintraperitoneal tumors afterintraperitoneal cisplatin treatment

  • Gerrit Los
  • Peter H. A. Mutsaers
  • Willem J. M. Lenglet
  • Glenn S. Baldew
  • J. Gordon McVie
Original Articles Platinum Distribution, Cisplatin, Intraperitoneal


The spatial distribution of platinum (Pt) in the kidney was studied by an autoradiographic technique, in which cisplatin (CDDP) was replaced by195mPt-labeled CDDP, and by proton-induced X-ray emission (PIXE). Although both studies demonstrated comparable spatial distribution patterns, PIXE had the advantage that Pt concentrations could be determined quantitatively, in contrast to the relative information obtained by the autoradiographic technique. Using PIXE, the distribution of Pt in i.p. tumors was studied after i.p. administration of CDDP. The highest Pt concentrations were always found on the periphery of tumors, indicating that the periphery was exposed to a higher drug concentration than the center. Dose was correlated to the concentration of CDDP at both the center and the periphery (r=0.99).The Pt concentration in the periphery was usually higher by a factor of 2–3 after i.p. administration than after i.v. treatment, whereas in the center of the tumor no concentration difference could be detected. The penetration depth of CDDP lay between 1 and 2 mm and was calculated from the differences in Pt concentration after i.p. and i.v. treatment. This indicates that the effective advantage of i.p. chemotherapy with CDDP in cases of cancers limited to the peritoneal cavity is accentuated at the periphery of the tumor.


Platinum Spatial Distribution Cancer Research Distribution Pattern Drug Concentration 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Brenner DE (1986) Intraperitoneal chemotherapy: a review. J Clin Oncol 4: 1135Google Scholar
  2. 2.
    Bulger RE, Dobyan DC (1984) Proliferative lesions found in the rat kidney after a single dose of cisplatinum. J Natl Cancer Inst 73: 1235Google Scholar
  3. 3.
    Carter SK (1982) Cisplatin. Chemiotherapia 1: 83Google Scholar
  4. 4.
    Casper ES, Kelsen DP, Alcock NW, Lewis JL (1983) I.p. cisplatin in patients with malignant ascites: pharmacokinetic evaluation and comparison with the i.v. route. Cancer Treat Rep 7: 235Google Scholar
  5. 5.
    Choie DD, Longnecker DS, Delcampo AA (1981) Acute and chronic cisplatin nephropathy in rats. Lab Invest 44: 397Google Scholar
  6. 6.
    Chopra S, Kaufman JS, Jones TW, Hong WU, Gehr MU, Hamburger RJ, Flamenbaum W, Trump BF (1982)cis-Diamminedichloroplatinum induced acute renal failure in the rat. Kidney Int 21: 54Google Scholar
  7. 7.
    Dedrick RL, Myers CE, Bungay PM, DeVita VT (1978) Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cance. Cancer Treat Rep 62: 1Google Scholar
  8. 8.
    Dikhoff TGMH, Prins M, Hofman LJB (1982) Target preparation of biological specimens for SPIXE measurements. Nucl Instrum Methods 197:129Google Scholar
  9. 9.
    Dikhoff TGMH, Heide JA van der, Prins M, McVie JG (1983) Determination of platinum in human tissues with PIXE. IEEE Trans Nucl Sci 30: 1329Google Scholar
  10. 10.
    Dikhoff TGMH, Heide JA van der, McVie JG (1985) Topographic analysis of platinum levels in kidney slices from cisplatin treated patients. Nucl Instrum Methods B 10/11: 639Google Scholar
  11. 11.
    Dobyan, DC, Levi J, Jacobs C,Kosek J, Weiner MW (1980) Mechanism of cisplatinum nephrotoxicity: II. Morphologic observations. J Pharmacol Exp Ther 213: 551Google Scholar
  12. 12.
    Goldstein RS, Mayor GH (1983) The nephrotoxicity of cisplatin. Life Sci 32: 685Google Scholar
  13. 13.
    Howell SB, Pfeifle CE, Wung WE, Olshen RA, Lucas WE, Youg JL, Green M (1982) Intraperitoneal cisplatin with thiosulfate protection. Ann Intern Med 97: 845Google Scholar
  14. 14.
    Johansson TB, Akselsson R, Johansson SAE (1970) X-ray analysis: elemental trace analysis at the 10−12 g level. Nucl Instrum Methods 84: 141Google Scholar
  15. 15.
    Kemmenoe BH, Malspeis L (1987) Distribution of [2-14C]Merbarone in mice by autoradiography of whole-body cryosections. Cancer Res 47: 1135Google Scholar
  16. 16.
    Kroin JS, Penn RD (1982) Intracerebral chemotherapy: chronic microinfusion of cisplatin. Neurosurgery 10: 349Google Scholar
  17. 17.
    Lenglet WJM (1988) On the distribution of trace elements in biological material: studies based on the use of an accelator. Thesis, Free University, AmsterdamGoogle Scholar
  18. 18.
    Levin VA, Patlak CS, Landahl HD (1980) Heuristic modeling of drug delivery to malignant brain tumors. J Pharmacokinet Biopharm 8: 257Google Scholar
  19. 19.
    Los G, Mutsaers PHA, Vijgh WJF van der, Hamer CJD van der, McVie JG (1987) Platihum distribution in intraperitoneal tumors after intraperitoneal or intravenous chemotherapy. Proc Am Assoc Clin Oncol Abstr 160Google Scholar
  20. 20.
    Los G, Mutsaers PHA, Vijgh WJF van der, Baldew GS, Graf PW de, McVie JG (1989) Direct diffusion ofcis-diamminedichloroplatinum (II) in intraperitoneal tumors after intraperitoneal chemotherapy: a comparison with systemic chemotherapy. Cancer Res 49:3380Google Scholar
  21. 21.
    Madias NE, Harrington JT (1978) Platinum nephrotoxicity. Am J Med 65: 307Google Scholar
  22. 22.
    Makman M, Cleary S, Lucas WE, Howell SB (1985) Intraperitoneal chemotherapy with high dose cisplatin and cytosine arabinoside for refractory ovarian carcinoma and other malignancies principally involving the peritoneal cavity. J Clin Oncol 3: 925Google Scholar
  23. 23.
    McVie JG, Dikhoff TGMH, Heide J van der (1982) Tissue concentration of platinum after intraperitoneal administration in patients. Proc Am Assoc Cancer Res 26: 162Google Scholar
  24. 24.
    McVie JG, Dikhoff TGMH, Goeij JJM de, Hamer JA van der, Los G (1986) Detection of platinum in tumors by proton induced X-ray emission. Proceedings of the 5th NCI/EORTC Symposium on New Drugs in Cancer Therapy, Amsterdam, January 23, 1986Google Scholar
  25. 25.
    Morrison PF, Dedrick RL (1986) Transport of cisplatin in rat brain following microinfusion: an analysis. J Pharm Sci 75: 120Google Scholar
  26. 26.
    Ozols R (1985) Intraperitoneal chemotherapy in management of ovarian cancer. Semin Oncol 12: 75Google Scholar
  27. 27.
    Ozols RF, Locker GY, Doroshow JH (1979) Pharmacokinetics of Adriamycin and tissue penetration in murine ovarian carcinoma. Cancer Res 39: 3209Google Scholar
  28. 28.
    Speyer JL, Myers CE (1980) The use of peritoneal dialysis for delivery of chemotherapy to intraperitoneal malignancies. Recent Results Cancer Res 74: 264Google Scholar
  29. 29.
    Stewart DJ, Mikhael NZ, Nanji AA, Nair RC, Kacews S, Howard K, Hirte W, Maroun JA (1985) Renal and hepatic concentrations of platinum: relationship to cisplatin time, dose and nephrotoxicity. J Clin Oncol 3: 1251Google Scholar
  30. 30.
    Tay LV, Bregman CL, Masters BA, Williams PO (1988) Effects ofcis-diamminedichloroplatinum (II) on rabbit kidney in vivo and on rabbit renal proximal tubule cells in culture. Cancer Res 48: 2538Google Scholar
  31. 31.
    Ten Bokkel Huinink WW, Dubbelman R, Aartsen A, Franklin H, McVie JG (1985) Experimental and clinical results with intraperitoneal cisplatin. Semin Oncol 12: 43Google Scholar
  32. 32.
    Ward JM, Fauvie KA (1976) The nephrotoxic effects ofcis-diamminedichloroplatinum (II) (NSC-119875) in male 334 rats. Toxicol Appl Pharmacol 38: 535Google Scholar
  33. 33.
    Zedick MS, Sternberg SS (1974) A Model system for studies of colon carcinogenesis: Tumor induction by a single injection of methylazoxymethanol acetate. J Natl Cancer Inst 53: 1419Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Gerrit Los
    • 1
  • Peter H. A. Mutsaers
    • 2
  • Willem J. M. Lenglet
    • 3
  • Glenn S. Baldew
    • 4
  • J. Gordon McVie
    • 1
  1. 1.Department of Experimental ChemotherapyThe Netherlands Cancer InstituteAmsterdamThe Netherlands
  2. 2.Cyclotron LaboratoryEindhoven University of TechnologyEindhovenThe Netherlands
  3. 3.Department of PhysicsThe Free UniversityAmsterdamThe Netherlands
  4. 4.Department of RadiochemistryIRI, Interfaculty Reactor InstituteDelftThe Netherlands

Personalised recommendations