Abstract | PURPOSE: METHODS: Circulatory retention studies were performed in nontumor-bearing mice injected intravenously (i.v.) with 875 mg/kg of PEG-beta-CPT. Antitumor activity was evaluated both intraperitoneally (i.p.) and i.v. in nude mouse xenograft models. Biodistribution studies were performed in nude mice bearing colorectal carcinoma xenografts with tritium-labelled PEG-beta-CPT and CPT injected i.v. RESULTS:
PEG-beta-CPT had a blood t1/2alpha of approximately 6 min and a t1/2beta of 10.2 h. Significant antitumor activity was seen in all treated xenograft models. Biodistribution studies demonstrated that PEG-beta-CPT in saline provided more available labelled CPT in the circulation than unconjugated CPT dissolved in intralipid. In addition, it appeared that more labelled CPT accumulated in solid tumors when delivered in the PEG-beta-CPT form, with greater preference for tumor tissue than normal tissue. CONCLUSION: This soluble transport form of CPT and its underlying technology may have clinical application especially for the treatment of solid tumors.
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Authors | C D Conover, R B Greenwald, A Pendri, C W Gilbert, K L Shum |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 42
Issue 5
Pg. 407-14
( 1998)
ISSN: 0344-5704 [Print] Germany |
PMID | 9771956
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- Drug Carriers
- Prodrugs
- Tritium
- Polyethylene Glycols
- pegamotecan
- Glycine
- Camptothecin
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Topics |
- Animals
- Antineoplastic Agents, Phytogenic
(administration & dosage, pharmacokinetics, therapeutic use)
- Camptothecin
(administration & dosage, analogs & derivatives, pharmacokinetics, therapeutic use)
- Colorectal Neoplasms
(metabolism)
- Drug Carriers
- Glycine
(chemistry)
- Humans
- Injections, Intraperitoneal
- Injections, Intravenous
- Mice
- Mice, Nude
- Neoplasm Transplantation
- Polyethylene Glycols
(administration & dosage, chemistry, pharmacokinetics)
- Prodrugs
(administration & dosage, pharmacokinetics, therapeutic use)
- Tissue Distribution
- Tritium
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