Comparison of high-specific-activity ultratrace 123/131I-MIBG and carrier-added 123/131I-MIBG on efficacy, pharmacokinetics, and tissue distribution

John A Barrett, John L Joyal, Shawn M Hillier, Kevin P Maresca, Frank J Femia, James F Kronauge, Marie Boyd, Robert J Mairs, John W Babich

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Metaiodobenzylguanidine (MIBG) is an enzymatically stable synthetic analog of norepinephrine that when radiolabled with diagnostic ((123)I) or therapeutic ((131)I) isotopes has been shown to concentrate highly in sympathetically innervated tissues such as the heart and neuroendocrine tumors that possesses high levels of norepinephrine transporter (NET). As the transport of MIBG by NET is a saturable event, the specific activity of the preparation may have dramatic effects on both the efficacy and safety of the radiodiagnostic/radiotherapeutic. Using a solid labeling approach (Ultratrace), noncarrier-added radiolabeled MIBG can be efficiently produced. In this study, specific activities of >1200 mCi/micromol for (123)I and >1600 mCi/micromol for (131)I have been achieved. A series of studies were performed to assess the impact of cold carrier MIBG on the tissue distribution of (123/131)I-MIBG in the conscious rat and on cardiovascular parameters in the conscious instrumented dog. The present series of studies demonstrated that the carrier-free Ultratrace MIBG radiolabeled with either (123)I or (131)I exhibited similar tissue distribution to the carrier-added radiolabeled MIBG in all nontarget tissues. In tissues that express NETs, the higher the specific activity of the preparation the greater will be the radiopharmaceutical uptake. This was reflected by greater efficacy in the mouse neuroblastoma SK-N-BE(2c) xenograft model and less appreciable cardiovascular side-effects in dogs when the high-specific-activity radiopharmaceutical was used. The increased uptake and retention of Ultratrace (123/131)I-MIBG may translate into a superior diagnostic and therapeutic potential. Lastly, care must be taken when administering therapeutic doses of the current carrier-added (131)I-MIBG because of its potential to cause adverse cardiovascular side-effects, nausea, and vomiting.
LanguageEnglish
Pages299-308
Number of pages10
JournalCancer Biotherapy and Radiopharmaceuticals
Volume25
Issue number3
DOIs
Publication statusPublished - Jun 2010

Fingerprint

Tissue Distribution
Norepinephrine Plasma Membrane Transport Proteins
Radiopharmaceuticals
Pharmacokinetics
Dogs
Heart Neoplasms
Neuroendocrine Tumors
Neuroblastoma
Heterografts
Isotopes
Nausea
Vomiting
Norepinephrine
Therapeutics
Safety

Keywords

  • 3-Iodobenzylguanidine
  • animal structures
  • blood pressure
  • bone marrow
  • bradycardia
  • dogs
  • electrocardiography
  • heart
  • heart rate
  • iodine radioisotopes
  • isotope labeling
  • myocardium
  • neuroblastoma
  • radiopharmaceuticals
  • tissue distribution
  • xenograft model antitumor Assays

Cite this

Barrett, John A ; Joyal, John L ; Hillier, Shawn M ; Maresca, Kevin P ; Femia, Frank J ; Kronauge, James F ; Boyd, Marie ; Mairs, Robert J ; Babich, John W. / Comparison of high-specific-activity ultratrace 123/131I-MIBG and carrier-added 123/131I-MIBG on efficacy, pharmacokinetics, and tissue distribution. In: Cancer Biotherapy and Radiopharmaceuticals . 2010 ; Vol. 25, No. 3. pp. 299-308.
@article{7d18b16168f8445eb6333b8da0f39282,
title = "Comparison of high-specific-activity ultratrace 123/131I-MIBG and carrier-added 123/131I-MIBG on efficacy, pharmacokinetics, and tissue distribution",
abstract = "Metaiodobenzylguanidine (MIBG) is an enzymatically stable synthetic analog of norepinephrine that when radiolabled with diagnostic ((123)I) or therapeutic ((131)I) isotopes has been shown to concentrate highly in sympathetically innervated tissues such as the heart and neuroendocrine tumors that possesses high levels of norepinephrine transporter (NET). As the transport of MIBG by NET is a saturable event, the specific activity of the preparation may have dramatic effects on both the efficacy and safety of the radiodiagnostic/radiotherapeutic. Using a solid labeling approach (Ultratrace), noncarrier-added radiolabeled MIBG can be efficiently produced. In this study, specific activities of >1200 mCi/micromol for (123)I and >1600 mCi/micromol for (131)I have been achieved. A series of studies were performed to assess the impact of cold carrier MIBG on the tissue distribution of (123/131)I-MIBG in the conscious rat and on cardiovascular parameters in the conscious instrumented dog. The present series of studies demonstrated that the carrier-free Ultratrace MIBG radiolabeled with either (123)I or (131)I exhibited similar tissue distribution to the carrier-added radiolabeled MIBG in all nontarget tissues. In tissues that express NETs, the higher the specific activity of the preparation the greater will be the radiopharmaceutical uptake. This was reflected by greater efficacy in the mouse neuroblastoma SK-N-BE(2c) xenograft model and less appreciable cardiovascular side-effects in dogs when the high-specific-activity radiopharmaceutical was used. The increased uptake and retention of Ultratrace (123/131)I-MIBG may translate into a superior diagnostic and therapeutic potential. Lastly, care must be taken when administering therapeutic doses of the current carrier-added (131)I-MIBG because of its potential to cause adverse cardiovascular side-effects, nausea, and vomiting.",
keywords = "3-Iodobenzylguanidine, animal structures, blood pressure , bone marrow, bradycardia, dogs, electrocardiography, heart, heart rate, iodine radioisotopes, isotope labeling, myocardium, neuroblastoma, radiopharmaceuticals, tissue distribution, xenograft model antitumor Assays",
author = "Barrett, {John A} and Joyal, {John L} and Hillier, {Shawn M} and Maresca, {Kevin P} and Femia, {Frank J} and Kronauge, {James F} and Marie Boyd and Mairs, {Robert J} and Babich, {John W}",
year = "2010",
month = "6",
doi = "10.1089/cbr.2009.0695",
language = "English",
volume = "25",
pages = "299--308",
journal = "Cancer Biotherapy and Radiopharmaceuticals",
issn = "1084-9785",
number = "3",

}

Comparison of high-specific-activity ultratrace 123/131I-MIBG and carrier-added 123/131I-MIBG on efficacy, pharmacokinetics, and tissue distribution. / Barrett, John A; Joyal, John L; Hillier, Shawn M; Maresca, Kevin P; Femia, Frank J; Kronauge, James F; Boyd, Marie; Mairs, Robert J; Babich, John W.

In: Cancer Biotherapy and Radiopharmaceuticals , Vol. 25, No. 3, 06.2010, p. 299-308.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Comparison of high-specific-activity ultratrace 123/131I-MIBG and carrier-added 123/131I-MIBG on efficacy, pharmacokinetics, and tissue distribution

AU - Barrett, John A

AU - Joyal, John L

AU - Hillier, Shawn M

AU - Maresca, Kevin P

AU - Femia, Frank J

AU - Kronauge, James F

AU - Boyd, Marie

AU - Mairs, Robert J

AU - Babich, John W

PY - 2010/6

Y1 - 2010/6

N2 - Metaiodobenzylguanidine (MIBG) is an enzymatically stable synthetic analog of norepinephrine that when radiolabled with diagnostic ((123)I) or therapeutic ((131)I) isotopes has been shown to concentrate highly in sympathetically innervated tissues such as the heart and neuroendocrine tumors that possesses high levels of norepinephrine transporter (NET). As the transport of MIBG by NET is a saturable event, the specific activity of the preparation may have dramatic effects on both the efficacy and safety of the radiodiagnostic/radiotherapeutic. Using a solid labeling approach (Ultratrace), noncarrier-added radiolabeled MIBG can be efficiently produced. In this study, specific activities of >1200 mCi/micromol for (123)I and >1600 mCi/micromol for (131)I have been achieved. A series of studies were performed to assess the impact of cold carrier MIBG on the tissue distribution of (123/131)I-MIBG in the conscious rat and on cardiovascular parameters in the conscious instrumented dog. The present series of studies demonstrated that the carrier-free Ultratrace MIBG radiolabeled with either (123)I or (131)I exhibited similar tissue distribution to the carrier-added radiolabeled MIBG in all nontarget tissues. In tissues that express NETs, the higher the specific activity of the preparation the greater will be the radiopharmaceutical uptake. This was reflected by greater efficacy in the mouse neuroblastoma SK-N-BE(2c) xenograft model and less appreciable cardiovascular side-effects in dogs when the high-specific-activity radiopharmaceutical was used. The increased uptake and retention of Ultratrace (123/131)I-MIBG may translate into a superior diagnostic and therapeutic potential. Lastly, care must be taken when administering therapeutic doses of the current carrier-added (131)I-MIBG because of its potential to cause adverse cardiovascular side-effects, nausea, and vomiting.

AB - Metaiodobenzylguanidine (MIBG) is an enzymatically stable synthetic analog of norepinephrine that when radiolabled with diagnostic ((123)I) or therapeutic ((131)I) isotopes has been shown to concentrate highly in sympathetically innervated tissues such as the heart and neuroendocrine tumors that possesses high levels of norepinephrine transporter (NET). As the transport of MIBG by NET is a saturable event, the specific activity of the preparation may have dramatic effects on both the efficacy and safety of the radiodiagnostic/radiotherapeutic. Using a solid labeling approach (Ultratrace), noncarrier-added radiolabeled MIBG can be efficiently produced. In this study, specific activities of >1200 mCi/micromol for (123)I and >1600 mCi/micromol for (131)I have been achieved. A series of studies were performed to assess the impact of cold carrier MIBG on the tissue distribution of (123/131)I-MIBG in the conscious rat and on cardiovascular parameters in the conscious instrumented dog. The present series of studies demonstrated that the carrier-free Ultratrace MIBG radiolabeled with either (123)I or (131)I exhibited similar tissue distribution to the carrier-added radiolabeled MIBG in all nontarget tissues. In tissues that express NETs, the higher the specific activity of the preparation the greater will be the radiopharmaceutical uptake. This was reflected by greater efficacy in the mouse neuroblastoma SK-N-BE(2c) xenograft model and less appreciable cardiovascular side-effects in dogs when the high-specific-activity radiopharmaceutical was used. The increased uptake and retention of Ultratrace (123/131)I-MIBG may translate into a superior diagnostic and therapeutic potential. Lastly, care must be taken when administering therapeutic doses of the current carrier-added (131)I-MIBG because of its potential to cause adverse cardiovascular side-effects, nausea, and vomiting.

KW - 3-Iodobenzylguanidine

KW - animal structures

KW - blood pressure

KW - bone marrow

KW - bradycardia

KW - dogs

KW - electrocardiography

KW - heart

KW - heart rate

KW - iodine radioisotopes

KW - isotope labeling

KW - myocardium

KW - neuroblastoma

KW - radiopharmaceuticals

KW - tissue distribution

KW - xenograft model antitumor Assays

U2 - 10.1089/cbr.2009.0695

DO - 10.1089/cbr.2009.0695

M3 - Article

VL - 25

SP - 299

EP - 308

JO - Cancer Biotherapy and Radiopharmaceuticals

T2 - Cancer Biotherapy and Radiopharmaceuticals

JF - Cancer Biotherapy and Radiopharmaceuticals

SN - 1084-9785

IS - 3

ER -