Biokinetic and dosimetric studies of 188Re-hyaluronic acid

a new radiopharmaceutical for treatment of hepatocellular carcinoma

Laura Meléndez-Alafort, Anna Nadali, Elena Zangoni, Alessandra Banzato, Maria Rondina, Antonio Rosato, Ulderico Mazzi

Research output: Contribution to journalArticle

12 Citations (Scopus)

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: 188Re-HA was prepared by a direct labelling method to produce a ReO(O-COO)2-type coordination complex. 188Re-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 188Re-HA was determined. Results: A stable complex of 188Re-HA was obtained with high radiochemical purity (>90%) and low serum protein binding (2%). Biokinetic studies showed a rapid blood clearance (T1/2α=21 min). Four hours after administration, 188Re-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 ∼40 Gy after 7.4 MBq of 188Re-HA injection. Conclusions: 188Re-HA complex showed good stability, pharmacokinetic and dosimetric characteristics that confirm its potential as a new agent for HCC radiation therapy.

Original languageEnglish
Pages (from-to)693-701
Number of pages9
JournalNuclear Medicine and Biology
Volume36
Issue number6
DOIs
Publication statusPublished - Aug 2009

Fingerprint

Radiopharmaceuticals
Hyaluronic Acid
Hepatocellular Carcinoma
Maximum Tolerated Dose
Liver
CD44 Antigens
Rhenium
Coordination Complexes
Therapeutics
Liver Neoplasms
Protein Binding
Aspartic Acid
Radioisotopes
Alanine
Cysteine
Blood Proteins
Neoplasms
Buffers
Radiotherapy
Pharmacokinetics

Keywords

  • Re-HA
  • Hepatocellular carcinoma
  • Radionuclide therapy
  • Rhenium-188 Hyaluronic acid

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Biokinetic and dosimetric studies of 188Re-hyaluronic acid : a new radiopharmaceutical for treatment of hepatocellular carcinoma. / Meléndez-Alafort, Laura; Nadali, Anna; Zangoni, Elena; Banzato, Alessandra; Rondina, Maria; Rosato, Antonio; Mazzi, Ulderico.

In: Nuclear Medicine and Biology, Vol. 36, No. 6, 08.2009, p. 693-701.

Research output: Contribution to journalArticle

Meléndez-Alafort, Laura ; Nadali, Anna ; Zangoni, Elena ; Banzato, Alessandra ; Rondina, Maria ; Rosato, Antonio ; Mazzi, Ulderico. / Biokinetic and dosimetric studies of 188Re-hyaluronic acid : a new radiopharmaceutical for treatment of hepatocellular carcinoma. In: Nuclear Medicine and Biology. 2009 ; Vol. 36, No. 6. pp. 693-701.
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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: 188Re-HA was prepared by a direct labelling method to produce a ReO(O-COO)2-type coordination complex. 188Re-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 188Re-HA was determined. Results: A stable complex of 188Re-HA was obtained with high radiochemical purity (>90{\%}) and low serum protein binding (2{\%}). Biokinetic studies showed a rapid blood clearance (T1/2α=21 min). Four hours after administration, 188Re-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 ∼40 Gy after 7.4 MBq of 188Re-HA injection. Conclusions: 188Re-HA complex showed good stability, pharmacokinetic and dosimetric characteristics that confirm its potential as a new agent for HCC radiation therapy.",
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T2 - a new radiopharmaceutical for treatment of hepatocellular carcinoma

AU - Meléndez-Alafort, Laura

AU - Nadali, Anna

AU - Zangoni, Elena

AU - Banzato, Alessandra

AU - Rondina, Maria

AU - Rosato, Antonio

AU - Mazzi, Ulderico

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N2 - 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: 188Re-HA was prepared by a direct labelling method to produce a ReO(O-COO)2-type coordination complex. 188Re-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 188Re-HA was determined. Results: A stable complex of 188Re-HA was obtained with high radiochemical purity (>90%) and low serum protein binding (2%). Biokinetic studies showed a rapid blood clearance (T1/2α=21 min). Four hours after administration, 188Re-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 ∼40 Gy after 7.4 MBq of 188Re-HA injection. Conclusions: 188Re-HA complex showed good stability, pharmacokinetic and dosimetric characteristics that confirm its potential as a new agent for HCC radiation therapy.

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