skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Comparison of the Anti-tumor Effects of Two Platinum Agents (Miriplatin and Fine-Powder Cisplatin)

Abstract

Purpose: This study was designed to evaluate the anti-tumor effects of miriplatin-lipidol and fine-powder cisplatin-lipiodol suspensions. Methods: Assessment of the cytotoxicity of two drugs was performed: a soluble derivative of miriplatin (DPC) and fine-powder cisplatin. We randomly divided 15 rabbits with transplanted VX2 liver tumors into three equal groups. They were infused via the proper hepatic artery with a miriplatin-lipiodol suspension (ML), a fine-powder cisplatin-lipiodol suspension (CL), or saline (control) and the tumor growth rate was determined on MR images acquired before and 7 days after treatment. The concentration of platinum (PCs) in blood was assayed immediately, and 10, 30, and 60 min, and 24 h and 7 days after drug administration. Its concentration in tumor and surrounding normal liver tissues was determined at 7 days postadministration. Results: At high concentrations, fine-powder cisplatin exhibited stronger cytotoxicity than DPC. At low concentrations, both agents manifested weak cytotoxicity. While there was no difference between the tumor growth rate of the ML and the CL groups, the difference between the controls and ML- and CL-treated rabbits was significant. The blood PCs peaked at 10 min and then gradually decreased over time. On the other hand, no platinum was detected at any point aftermore » the administration of ML. There was no difference between the ML and CL groups in the PCs in tumor tissues; however, in normal hepatic tissue, the PCs were higher in ML- than CL-treated rabbits. Conclusions: We confirmed the anti-tumor effect of ML and CL. There was no significant difference between the anti-tumor effect of ML and CL at 7 days postadministration.« less

Authors:
; ; ; ; ; ; ; ; ; ;  [1]
  1. Shiga University of Medical Science, Department of Radiology (Japan)
Publication Date:
OSTI Identifier:
21608562
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cardiovascular and Interventional Radiology; Journal Volume: 35; Journal Issue: 2; Other Information: DOI: 10.1007/s00270-011-0172-4; Copyright (c) 2012 Springer Science+Business Media, LLC and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE); Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ARTERIES; BLOOD; CONTROL; IMAGES; LIPIODOL; LIVER; NEOPLASMS; PLATINUM; POWDERS; SUSPENSIONS; TOXICITY; BIOLOGICAL MATERIALS; BLOOD VESSELS; BODY; BODY FLUIDS; CARDIOVASCULAR SYSTEM; CONTRAST MEDIA; DIGESTIVE SYSTEM; DISEASES; DISPERSIONS; ELEMENTS; GLANDS; MATERIALS; METALS; OILS; ORGANIC COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; ORGANIC IODINE COMPOUNDS; ORGANS; OTHER ORGANIC COMPOUNDS; PLATINUM METALS; TRANSITION ELEMENTS

Citation Formats

Watanabe, Shobu, E-mail: swat@belle.shiga-med.ac.jp, Nitta, Norihisa, E-mail: r34nitta@belle.shiga-med.ac.jp, Ohta, Shinichi, E-mail: junryuhei@yahoo.co.jp, Sonoda, Akinaga, E-mail: akinaga@belle.shiga-med.ac.jp, Otani, Hideji, E-mail: otani@belle.shiga-med.ac.jp, Tomozawa, Yuki, E-mail: tomozawa@belle.shiga-med.ac.jp, Nitta-Seko, Ayumi, E-mail: sekoayumi@yahoo.co.jp, Tsuchiya, Keiko, E-mail: keikot@belle.shiga-med.ac.jp, Tanka, Toyohiko, E-mail: toyohiko@belle.shiga-med.ac.jp, Takahashi, Masashi, E-mail: masashi@belle.shiga-med.ac.jp, and Murata, Kiyoshi, E-mail: murata@belle.shiga-med.ac.jp. Comparison of the Anti-tumor Effects of Two Platinum Agents (Miriplatin and Fine-Powder Cisplatin). United States: N. p., 2012. Web. doi:10.1007/S00270-011-0172-4.
Watanabe, Shobu, E-mail: swat@belle.shiga-med.ac.jp, Nitta, Norihisa, E-mail: r34nitta@belle.shiga-med.ac.jp, Ohta, Shinichi, E-mail: junryuhei@yahoo.co.jp, Sonoda, Akinaga, E-mail: akinaga@belle.shiga-med.ac.jp, Otani, Hideji, E-mail: otani@belle.shiga-med.ac.jp, Tomozawa, Yuki, E-mail: tomozawa@belle.shiga-med.ac.jp, Nitta-Seko, Ayumi, E-mail: sekoayumi@yahoo.co.jp, Tsuchiya, Keiko, E-mail: keikot@belle.shiga-med.ac.jp, Tanka, Toyohiko, E-mail: toyohiko@belle.shiga-med.ac.jp, Takahashi, Masashi, E-mail: masashi@belle.shiga-med.ac.jp, & Murata, Kiyoshi, E-mail: murata@belle.shiga-med.ac.jp. Comparison of the Anti-tumor Effects of Two Platinum Agents (Miriplatin and Fine-Powder Cisplatin). United States. doi:10.1007/S00270-011-0172-4.
Watanabe, Shobu, E-mail: swat@belle.shiga-med.ac.jp, Nitta, Norihisa, E-mail: r34nitta@belle.shiga-med.ac.jp, Ohta, Shinichi, E-mail: junryuhei@yahoo.co.jp, Sonoda, Akinaga, E-mail: akinaga@belle.shiga-med.ac.jp, Otani, Hideji, E-mail: otani@belle.shiga-med.ac.jp, Tomozawa, Yuki, E-mail: tomozawa@belle.shiga-med.ac.jp, Nitta-Seko, Ayumi, E-mail: sekoayumi@yahoo.co.jp, Tsuchiya, Keiko, E-mail: keikot@belle.shiga-med.ac.jp, Tanka, Toyohiko, E-mail: toyohiko@belle.shiga-med.ac.jp, Takahashi, Masashi, E-mail: masashi@belle.shiga-med.ac.jp, and Murata, Kiyoshi, E-mail: murata@belle.shiga-med.ac.jp. 2012. "Comparison of the Anti-tumor Effects of Two Platinum Agents (Miriplatin and Fine-Powder Cisplatin)". United States. doi:10.1007/S00270-011-0172-4.
@article{osti_21608562,
title = {Comparison of the Anti-tumor Effects of Two Platinum Agents (Miriplatin and Fine-Powder Cisplatin)},
author = {Watanabe, Shobu, E-mail: swat@belle.shiga-med.ac.jp and Nitta, Norihisa, E-mail: r34nitta@belle.shiga-med.ac.jp and Ohta, Shinichi, E-mail: junryuhei@yahoo.co.jp and Sonoda, Akinaga, E-mail: akinaga@belle.shiga-med.ac.jp and Otani, Hideji, E-mail: otani@belle.shiga-med.ac.jp and Tomozawa, Yuki, E-mail: tomozawa@belle.shiga-med.ac.jp and Nitta-Seko, Ayumi, E-mail: sekoayumi@yahoo.co.jp and Tsuchiya, Keiko, E-mail: keikot@belle.shiga-med.ac.jp and Tanka, Toyohiko, E-mail: toyohiko@belle.shiga-med.ac.jp and Takahashi, Masashi, E-mail: masashi@belle.shiga-med.ac.jp and Murata, Kiyoshi, E-mail: murata@belle.shiga-med.ac.jp},
abstractNote = {Purpose: This study was designed to evaluate the anti-tumor effects of miriplatin-lipidol and fine-powder cisplatin-lipiodol suspensions. Methods: Assessment of the cytotoxicity of two drugs was performed: a soluble derivative of miriplatin (DPC) and fine-powder cisplatin. We randomly divided 15 rabbits with transplanted VX2 liver tumors into three equal groups. They were infused via the proper hepatic artery with a miriplatin-lipiodol suspension (ML), a fine-powder cisplatin-lipiodol suspension (CL), or saline (control) and the tumor growth rate was determined on MR images acquired before and 7 days after treatment. The concentration of platinum (PCs) in blood was assayed immediately, and 10, 30, and 60 min, and 24 h and 7 days after drug administration. Its concentration in tumor and surrounding normal liver tissues was determined at 7 days postadministration. Results: At high concentrations, fine-powder cisplatin exhibited stronger cytotoxicity than DPC. At low concentrations, both agents manifested weak cytotoxicity. While there was no difference between the tumor growth rate of the ML and the CL groups, the difference between the controls and ML- and CL-treated rabbits was significant. The blood PCs peaked at 10 min and then gradually decreased over time. On the other hand, no platinum was detected at any point after the administration of ML. There was no difference between the ML and CL groups in the PCs in tumor tissues; however, in normal hepatic tissue, the PCs were higher in ML- than CL-treated rabbits. Conclusions: We confirmed the anti-tumor effect of ML and CL. There was no significant difference between the anti-tumor effect of ML and CL at 7 days postadministration.},
doi = {10.1007/S00270-011-0172-4},
journal = {Cardiovascular and Interventional Radiology},
number = 2,
volume = 35,
place = {United States},
year = 2012,
month = 4
}
  • For imaging or radiotherapy, {sup 64}Cu (T{sub 1/2}=12.8 h) has advantages over {sup 67}Cu (T{sub 1/2}=62h) that include wider availibility, lower cost, and a higher specific activity. {sup 67}Cu- and {sup 64}Cu- labeled monoclonal antibody (MAb) 1A3 showed similar lethal efficiencies in vitro to LS174T human colon cancer cells. To compare the lethal effiencies of these agents in vivo, 200 or 400 {mu}Ci of {sup 67}Cu-labeled Mab 1A3 and 500, 1000 or 2000 {mu}Ci of {sup 64}Cu-labeled 1A3 were administered into hamsters carrying 2 day old GW-39 human colon tumors in their thigh musculature. In another group of hamsters, {supmore » 67}Cu- and {sup 64}Cu-labeled non-specific Mab MOPC were also administered in corresponding amounts. A control group was injected with saline solution. At all doses, hamsters that were given either {sup 64}Cu- or {sup 67}Cu-labeled 1A3 showed inhibition of tumor growth over hamsters injected with either saline or {sup 64}Cu- or {sup 67}Cu-labeled MOPC. Tumor weights in hamsters administered with 2000 {mu}Ci of {sup 64}Cu-1A3 showed an 11-fold decrease over tumors in hamsters given saline (0.184 {plus_minus} 0.106 (n=3) vs 2.056 {plus_minus} 0.369 (n=10)), and a 5-fold decrease over those where {sup 64}Cu-MOPC was administered (0.184 {plus_minus} 0.106 (n=3) vs 0.961 {plus_minus} 0.228 (n=4)). In hamsters injected with 400 {mu}Ci {sup 67}Cu-1A3, a 13-fold decrease in tumor weight was observed over control hamsters given saline (0.345 {plus_minus} 0.129 (n=5)vs 4.457 {plus_minus}0.405 (n=10)), and a 7-fold decrease was observed when {sup 67}Cu-MOPC was injected (0.345 {plus_minus} 0.129 (n=5) vs 2.507 {plus_minus} 1.064 (n=5)). Given the 5-fold difference in half-life between {sup 67}Cu and {sup 64}Cu, at corresponding doses the inhibition of tumor growth was similar. These initial experiments indicate that {sup 64}Cu has a radiotherapeutic potential comparable to {sup 67}Cu when labeled to Mab 1A3.« less
  • The phorbol esters 12-O-tetradecanoylphorbol-13-acetate (TPA) and 12-O-hexadecanoylphorbol-13 acetate (HPA) are not only potent tumor promoters but also potent stimulators of epidermal DNA synthesis and ornithine decarboxylase (ODC) activity in adult mice. However, when applied topically to newborn mice, TPA and HPA have essentially no effect on epidermal and dermal DNA synthesis or on epidermal ODC activity. Exposure of primary cultures of newborn mouse epidermal cells to TPA or HPA markedly stimulated both DNA synthesis and ODC activity. The anti-inflammatory steroids dexamethasone and fluocinolone acetonide (FA) were found to be potent inhibitors of tumor promotion and epidermal DNA synthesis in adultmore » mice. However, when applied topically to newborn mice, FA did not inhibit epidermal or dermal DNA synthesis but stimulated it approximately twofold at 48 hours after FA treatment. In primary cultures of epidermal cells from newborn mice, treatment with dexamethasone or FA caused an early stimulation of DNA synthesis followed by a 50% inhibition of DNA synthesis 2 to 3 days after a 1-hour pulse treatment. Also, DNA synthesis was moderately inhibited when FA was added to primary cultures of dermal fibroblasts. In their reaction to tumor promoters, epidermal cells in culture behaved more like adult than newborn mouse epidermis in vivo, whereas anti-inflammatory steroids gave an intermediate response.« less
  • The effects of various clinically used anti-inflammatory agents on mouse skin tumorigenesis and aryl hydrocarbon hydroxylase (AHH) were investigated. Oxyphenbutazone, a nonsteroidal anti-inflammatory agent, inhibited 3-methylcholanthrene (MC) tumor initiation but was less effective than the steroidal anti-inflammatory agent, dexamethasone. Oxyphenbutazone was not found to induce AHH activity in mouse epidermis, whereas Indomethacin and Seclazone had a slight inducing effect. When these agents were added directly to the in vitro AHH assay, they did not inhibit AHH activity. However, additional experiments have shown a decreased epidermally mediated covalent binding of MC to DNA in vitro when the epidermal homogenates were isolatedmore » from mice pretreated with either dexamethasone or oxyphenbutazone and MC at 3 or 12 hr before killing.« less
  • PurposeThe purpose of this study is to evaluate the pharmacokinetics and histopathological findings of transarterial chemoembolization (TACE) using cisplatin powder mixed with degradable starch microspheres (DSM) (Cis/DSM-TACE) compared with cisplatin arterial infusion (Cis-AI).Materials and MethodsEighteen rabbits with VX2 liver tumors were divided into two groups: Cis/DSM-TACE (n = 9) and Cis-AI (n = 9) groups. In the Cis/DSM-TACE group, a mixture of cisplatin powder and DSM was injected until stasis of hepatic arterial flow was achieved. In the Cis-AI group, cisplatin solution was infused.ResultsThe platinum concentrations in VX2 tumors in the Cis/DSM-TACE group at 24 and 72 h were significantly elevated compared with those inmore » the Cis-AI group (P = .016 and .019, respectively). There were no significant differences in the platinum concentrations in plasma. Histopathological examination revealed the presence of several microspheres inside the tumors at 1 h, which completely disappeared at 24 h. Tumor cell apoptosis at 1 h in the Cis/DSM-TACE group was more frequently observed compared with that in the Cis-AI group (P = .006).ConclusionsTACE using cisplatin powder mixed with DSM provides a higher drug concentration in tumors, thereby achieving stronger antitumor effects compared with arterial infusion of cisplatin solution.« less
  • Whereas the interaction between radiation and platinum complexes has never been pronounced in radiobiological experiments (to 30 Gy in mammalian cells), there have been reports of interest in this combination in the clinic, where fractionated doses of approximately 2 Gy are used. Our studies on the marked interaction in hypoxia at the 80% survival level (1-2.5 Gy) with cisplatin have been extended to second generation platinum drugs of clinical interest. The studies in the lower radiation dose region have been facilitated by the use of the cell analyzer DMIPS to identify individual cells and follow them microscopically to assess formore » clonogenic ability. Chinese hamster V79 cells were used, which were exposed to drug for 1 hr prior to irradiation in hypoxia (or air). None of the drugs give an enhancement ratio (ER) greater than 1.3 in the high radiation dose region, whereas all can produce ER80% (ER calculated at iso-survival of 80%) of 2 or higher at low doses in hypoxic cells. The enhancement of radiation kill in oxic V79 cells (ER's to 1.1 at 1-2% S) disappears at low doses (ER80% = 1.0) except for tetraplatin, where a moderate ER80% (to 1.64) was measured. Comparison of the hypoxic interaction on a concentration basis suggests that cisplatin is the best drug at low x-ray doses and low concentrations, but the interaction reaches a plateau at ER80% approximately 2.0. Tetraplatin continues to give better interaction with increasing concentration (up to ER80% = 3.7 at 25 microM). Interaction of radiation with the less toxic drugs, iproplatin and carboplatin, used at around 100 microM can be improved by longer exposure times prior to irradiation. Comparison on the basis of toxicity, for which the plating efficiency was used, suggests that cisplatin gives a better interaction than the three newer drugs for a given level of toxicity in hypoxic V79 cells.« less