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Pharmacokinetics and Dosimetry of 111In/188Re-Labeled PEGylated Liposomal Drugs in Two Colon Carcinoma-Bearing Mouse Models

PEGylated liposomes are important drug carriers for nanomedicine cancer therapy. PEGylated liposomes can encapsulate radio- and chemo-drugs and passively target tumor sites via enhanced permeability and retention effect. This study estimated the pharmacokinetics and dosimetry after administration of... Full description

Journal Title: Cancer Biotherapy & Radiopharmaceuticals 01 June 2011, Vol.26(3), pp.373-380
Main Author: Lin, Yi-Yu
Other Authors: Chang, Chih-Hsien , Li, Jia-Je , Stabin, Michael G , Chang, Ya-Jen , Chen, Liang-Cheng , Lin, Ming-Hsien , Tseng, Yun-Long , Lin, Wuu-Jyh , Lee, Te-Wei , Ting, Gann , Chang, Cheng Allen , Chen, Fu-Du , Wang, Hsin-Ell
Format: Electronic Article Electronic Article
Language: English
Subjects:
C26
ID: ISSN: 1084-9785 ; E-ISSN: 1557-8852 ; DOI: 10.1089/cbr.2010.0906
Link: https://www.liebertpub.com/doi/abs/10.1089/cbr.2010.0906
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recordid: maryannliebert_s10_1089_cbr_2010_0906
title: Pharmacokinetics and Dosimetry of 111In/188Re-Labeled PEGylated Liposomal Drugs in Two Colon Carcinoma-Bearing Mouse Models
format: Article
creator:
  • Lin, Yi-Yu
  • Chang, Chih-Hsien
  • Li, Jia-Je
  • Stabin, Michael G
  • Chang, Ya-Jen
  • Chen, Liang-Cheng
  • Lin, Ming-Hsien
  • Tseng, Yun-Long
  • Lin, Wuu-Jyh
  • Lee, Te-Wei
  • Ting, Gann
  • Chang, Cheng Allen
  • Chen, Fu-Du
  • Wang, Hsin-Ell
subjects:
  • Original Articles
  • C26
  • Dosimetry
  • Doxorubicin
  • Pegylated Liposomes
  • Radionuclide Therapy
  • Vinorelbine
  • Medicine
  • Pharmacy, Therapeutics, & Pharmacology
ispartof: Cancer Biotherapy & Radiopharmaceuticals, 01 June 2011, Vol.26(3), pp.373-380
description: PEGylated liposomes are important drug carriers for nanomedicine cancer therapy. PEGylated liposomes can encapsulate radio- and chemo-drugs and passively target tumor sites via enhanced permeability and retention effect. This study estimated the pharmacokinetics and dosimetry after administration of radio-chemotherapeutics ( 111 In-labeled vinorelbine [VNB]-encapsulated liposomes, InVNBL, and 188 Re-labeled doxorubicin [DXR]-encapsulated liposomes, ReDXRL) for radionuclide therapy in two colon carcinoma-bearing mouse models. A C26 colon carcinoma tumor/ascites mouse model and a subcutaneous solid tumor-bearing mouse model were employed. Biodistribution studies of InVNBL and ReDXRL after intraperitoneal administration in tumor/ascites-bearing mice (protocol A) and intravenous administration in subcutaneous solid tumor-bearing mice (protocol B) were performed. The radiation dose to normal tissues and tumors were calculated based on the results of distribution studies in mice, using the OLINDA/EXM program. The cumulated activities in most organs after administration of InVNBL in either the tumor/ascites-bearing mice (protocol A) or the subcutaneous solid tumor-bearing mice (protocol B) were higher than those of ReDXRL. Higher tumor-to - normal-tissues absorption dose ratios (T/NTs) were observed after administration of InVNBL than those of ReDXRL for protocol A. The T/NTs for the liver, spleen, and red marrow after injection of InVNBL for protocol B were similar to those of ReDXRL. The critical organ was found to be red marrow, and thus the red marrow absorption dose defined the recommended maximum administration activity of these liposomal drugs. Characterization of pharmacokinetics and dosimetry is needed to select the appropriate radiotherapeutics for specific tumor treatment applications. The results suggest that InVNBL is a promising therapeutic agent, which is as good as ReDXRL, in two mouse tumor models.
language: eng
source:
identifier: ISSN: 1084-9785 ; E-ISSN: 1557-8852 ; DOI: 10.1089/cbr.2010.0906
fulltext: fulltext
issn:
  • 1084-9785
  • 10849785
  • 1557-8852
  • 15578852
url: Link


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titlePharmacokinetics and Dosimetry of 111In/188Re-Labeled PEGylated Liposomal Drugs in Two Colon Carcinoma-Bearing Mouse Models
creatorLin, Yi-Yu ; Chang, Chih-Hsien ; Li, Jia-Je ; Stabin, Michael G ; Chang, Ya-Jen ; Chen, Liang-Cheng ; Lin, Ming-Hsien ; Tseng, Yun-Long ; Lin, Wuu-Jyh ; Lee, Te-Wei ; Ting, Gann ; Chang, Cheng Allen ; Chen, Fu-Du ; Wang, Hsin-Ell
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subjectOriginal Articles ; C26 ; Dosimetry ; Doxorubicin ; Pegylated Liposomes ; Radionuclide Therapy ; Vinorelbine ; Medicine ; Pharmacy, Therapeutics, & Pharmacology
descriptionPEGylated liposomes are important drug carriers for nanomedicine cancer therapy. PEGylated liposomes can encapsulate radio- and chemo-drugs and passively target tumor sites via enhanced permeability and retention effect. This study estimated the pharmacokinetics and dosimetry after administration of radio-chemotherapeutics ( 111 In-labeled vinorelbine [VNB]-encapsulated liposomes, InVNBL, and 188 Re-labeled doxorubicin [DXR]-encapsulated liposomes, ReDXRL) for radionuclide therapy in two colon carcinoma-bearing mouse models. A C26 colon carcinoma tumor/ascites mouse model and a subcutaneous solid tumor-bearing mouse model were employed. Biodistribution studies of InVNBL and ReDXRL after intraperitoneal administration in tumor/ascites-bearing mice (protocol A) and intravenous administration in subcutaneous solid tumor-bearing mice (protocol B) were performed. The radiation dose to normal tissues and tumors were calculated based on the results of distribution studies in mice, using the OLINDA/EXM program. The cumulated activities in most organs after administration of InVNBL in either the tumor/ascites-bearing mice (protocol A) or the subcutaneous solid tumor-bearing mice (protocol B) were higher than those of ReDXRL. Higher tumor-to - normal-tissues absorption dose ratios (T/NTs) were observed after administration of InVNBL than those of ReDXRL for protocol A. The T/NTs for the liver, spleen, and red marrow after injection of InVNBL for protocol B were similar to those of ReDXRL. The critical organ was found to be red marrow, and thus the red marrow absorption dose defined the recommended maximum administration activity of these liposomal drugs. Characterization of pharmacokinetics and dosimetry is needed to select the appropriate radiotherapeutics for specific tumor treatment applications. The results suggest that InVNBL is a promising therapeutic agent, which is as good as ReDXRL, in two mouse tumor models.
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