Platinum distribution in intraperitoneal tumors after intraperitoneal cisplatin treatment.
The spatial distribution of platinum (Pt) in the kidney was studied by an autoradiographic technique, in which cisplatin (CDDP) was replaced by 195mPt-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.
Los
G
G
The Netherlands Cancer Institute, Department of Experimental Chemotherapy, Amsterdam.
Mutsaers
P H
PH
Lenglet
W J
WJ
Baldew
G S
GS
McVie
J G
JG
D000818:Animals; D001345:Autoradiography; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008297:Male; D010534:Peritoneal Neoplasms / Q000378:metabolism*; D010984:Platinum / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013052:Spectrometry, X-Ray Emission; D014018:Tissue Distribution
D010984:Platinum; D002945:Cisplatin