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Biokinetic and dosimetric studies of {sup 188}Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical. Methods: {sup 188}Re-HA was prepared by a direct labelling method to produce a ReO(O-COO){sub 2}-type coordination complex. {sup 188}Re-HA protein binding and its stability in saline, phosphate buffer, human serum and cysteine solutions were determined. Biokinetic and dosimetric data were estimated in healthy mice (n=60) using the Medical Internal Radiation Dose methodology and mouse model beta-absorbed fractions. To evaluate liver toxicity, alanine aminotranferase (AST) and aspartate aminotranferase (ALT) levels in mice were assessed and the liver maximum tolerated dose (MTD) of {sup 188}Re-HA was determined. Results: A stable complex of {sup 188}Re-HA was obtained with high radiochemical purity (>90%) and low serum protein binding (2%). Biokinetic studies showed a rapid blood clearance (T{sub 1/2}{alpha}=21 min). Four hours after administration, {sup 188}Re-HA was almost totally removed from the blood by  More>>
Authors:
Melendez-Alafort, Laura; [1]  Nadali, Anna; Zangoni, Elena; [1]  Banzato, Alessandra; Rondina, Maria; [2]  Rosato, Antonio; [2]  Istituto Oncologico Veneto, IOV, Padova, Padua (Italy)]; Mazzi, Ulderico [1] 
  1. Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy)
  2. Dipartimento di Scienze Oncologiche e Chirurgiche, Universita degli Studi di Padova, Padua (Italy)
Publication Date:
Aug 15, 2009
Product Type:
Journal Article
Resource Relation:
Journal Name: Nuclear Medicine and Biology; Journal Volume: 36; Journal Issue: 6; Other Information: DOI: 10.1016/j.nucmedbio.2009.04.006; PII: S0969-8051(09)00117-6; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; HEPATOMAS; HYALURONIC ACID; LABELLING; LIVER; MICE; RADIOPHARMACEUTICALS; RADIOTHERAPY; RHENIUM 188
OSTI ID:
21280807
Country of Origin:
United Kingdom
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0969-8051; NMBIEO; TRN: GB09R6492026680
Availability:
Available from http://dx.doi.org/10.1016/j.nucmedbio.2009.04.006; INIS
Submitting Site:
GBN
Size:
page(s) 693-701
Announcement Date:
Apr 14, 2010

Citation Formats

Melendez-Alafort, Laura, Nadali, Anna, Zangoni, Elena, Banzato, Alessandra, Rondina, Maria, Rosato, Antonio, Istituto Oncologico Veneto, IOV, Padova, Padua (Italy)], and Mazzi, Ulderico. Biokinetic and dosimetric studies of {sup 188}Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma. United Kingdom: N. p., 2009. Web. doi:10.1016/j.nucmedbio.2009.04.006.
Melendez-Alafort, Laura, Nadali, Anna, Zangoni, Elena, Banzato, Alessandra, Rondina, Maria, Rosato, Antonio, Istituto Oncologico Veneto, IOV, Padova, Padua (Italy)], & Mazzi, Ulderico. Biokinetic and dosimetric studies of {sup 188}Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma. United Kingdom. doi:10.1016/j.nucmedbio.2009.04.006.
Melendez-Alafort, Laura, Nadali, Anna, Zangoni, Elena, Banzato, Alessandra, Rondina, Maria, Rosato, Antonio, Istituto Oncologico Veneto, IOV, Padova, Padua (Italy)], and Mazzi, Ulderico. 2009. "Biokinetic and dosimetric studies of {sup 188}Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma." United Kingdom. doi:10.1016/j.nucmedbio.2009.04.006. https://www.osti.gov/servlets/purl/10.1016/j.nucmedbio.2009.04.006.
@misc{etde_21280807,
title = {Biokinetic and dosimetric studies of {sup 188}Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma}
author = {Melendez-Alafort, Laura, Nadali, Anna, Zangoni, Elena, Banzato, Alessandra, Rondina, Maria, Rosato, Antonio, Istituto Oncologico Veneto, IOV, Padova, Padua (Italy)], and Mazzi, Ulderico}
abstractNote = {Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical. Methods: {sup 188}Re-HA was prepared by a direct labelling method to produce a ReO(O-COO){sub 2}-type coordination complex. {sup 188}Re-HA protein binding and its stability in saline, phosphate buffer, human serum and cysteine solutions were determined. Biokinetic and dosimetric data were estimated in healthy mice (n=60) using the Medical Internal Radiation Dose methodology and mouse model beta-absorbed fractions. To evaluate liver toxicity, alanine aminotranferase (AST) and aspartate aminotranferase (ALT) levels in mice were assessed and the liver maximum tolerated dose (MTD) of {sup 188}Re-HA was determined. Results: A stable complex of {sup 188}Re-HA was obtained with high radiochemical purity (>90%) and low serum protein binding (2%). Biokinetic studies showed a rapid blood clearance (T{sub 1/2}{alpha}=21 min). Four hours after administration, {sup 188}Re-HA was almost totally removed from the blood by the liver due to the selective uptake via HA-specific receptors (73.47{+-}5.11% of the injected dose). The liver MTD in mice was {approx}40 Gy after 7.4 MBq of {sup 188}Re-HA injection. Conclusions: {sup 188}Re-HA complex showed good stability, pharmacokinetic and dosimetric characteristics that confirm its potential as a new agent for HCC radiation therapy.}
doi = {10.1016/j.nucmedbio.2009.04.006}
journal = {Nuclear Medicine and Biology}
issue = {6}
volume = {36}
place = {United Kingdom}
year = {2009}
month = {Aug}
}