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Pharmacokinetics, radiation dosimetry, acute toxicity and automated synthesis of [(18)F]AmBF(3)-TATE
INTRODUCTION: [(18)F]AmBF(3)-TATE is a somatostatin agonist that selectively binds to somatostatin receptor subtype 2 (SSTR2). For clinical translation, pharmacokinetics, radiation dosimetry, and acute toxicity of [(18)F]AmBF(3)-TATE were assessed with good laboratory practice (GLP) standards. METHO...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080905/ https://www.ncbi.nlm.nih.gov/pubmed/32189151 http://dx.doi.org/10.1186/s13550-020-0611-9 |
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author | Lau, Joseph Pan, Jinhe Rousseau, Etienne Uribe, Carlos F. Seelam, Sudhakara Reddy Sutherland, Brent W. Perrin, David M. Lin, Kuo-Shyan Bénard, François |
author_facet | Lau, Joseph Pan, Jinhe Rousseau, Etienne Uribe, Carlos F. Seelam, Sudhakara Reddy Sutherland, Brent W. Perrin, David M. Lin, Kuo-Shyan Bénard, François |
author_sort | Lau, Joseph |
collection | PubMed |
description | INTRODUCTION: [(18)F]AmBF(3)-TATE is a somatostatin agonist that selectively binds to somatostatin receptor subtype 2 (SSTR2). For clinical translation, pharmacokinetics, radiation dosimetry, and acute toxicity of [(18)F]AmBF(3)-TATE were assessed with good laboratory practice (GLP) standards. METHODS: ICR mice were intravenously administered 0.8–2.0 MBq of [(18)F]AmBF(3)-TATE, with one group pre-injected with 100 μg of [(19)F]AmBF(3)-TATE 30 min before radiopharmaceutical administration to assess uptake specificity. The mice were euthanized at 0.5, 1, 2, or 4 h post-injection (p.i.). Blood and tissues were collected, weighed, and counted on a gamma counter to determine percentage injected dose per gram (%ID/g). Dosimetry was calculated based on biodistribution data using the mouse and human phantoms included in OLINDA. Acute toxicity was assessed in Sprague-Dawley rats at the dose of 0.742 mg/kg [(19)F]AmBF(3)-TATE, with a 14-day observation/recovery period. Blood chemistry parameters, gross, and histopathology were evaluated. Body weight change and food consumption were monitored. The production of [(18)F]AmBF(3)-TATE was automated on a Trasis AllinOne synthesis module. RESULTS: [(18)F]AmBF(3)-TATE was cleared through the renal and hepatobiliary pathway. At 1 h p.i., the pancreas (F, 15.7 ± 3.72 and M 14.3 ± 1.61 %ID/g), stomach (F, 15.3 ± 3.63 and M, 19.0 ± 3.49 %ID/g), and lungs (F, 9.26 ± 2.24 and M, 6.17 ± 6.04 %ID/g) were the organs with the highest specific uptake. Pre-injection with [(19)F]AmBF(3)-TATE significantly reduced pancreatic uptake (F, 0.13 ± 0.03 and M, 0.18 ± 0.09 %ID/g) at 1 h p.i. For dosimetry extrapolated to the average adult human, the bladder (0.027–0.030 mGy/MBq), pancreas (0.018–0.028 mGy/MBq), and lungs (0.006–0.013 mGy/MBq) are expected to receive the highest doses. No test-item related effects were observed upon evaluation of clinical observations, body weights, food consumption, clinical pathology, gross pathology, and histopathology for acute toxicity. [(18)F]AmBF(3)-TATE was produced at activity yields of 15.6 ± 4.59 GBq, average molar activity of 435 ± 162 GBq/μmol, and radiochemical purity of 98.0 ± 1.73% with the automated synthesizer. CONCLUSION: [(18)F]AmBF(3)-TATE binds specifically to SSTR2. At 1000× clinical dose, [(19)F]AmBF(3)-TATE was well tolerated with no treatment-related adverse effects. |
format | Online Article Text |
id | pubmed-7080905 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-70809052020-03-23 Pharmacokinetics, radiation dosimetry, acute toxicity and automated synthesis of [(18)F]AmBF(3)-TATE Lau, Joseph Pan, Jinhe Rousseau, Etienne Uribe, Carlos F. Seelam, Sudhakara Reddy Sutherland, Brent W. Perrin, David M. Lin, Kuo-Shyan Bénard, François EJNMMI Res Original Research INTRODUCTION: [(18)F]AmBF(3)-TATE is a somatostatin agonist that selectively binds to somatostatin receptor subtype 2 (SSTR2). For clinical translation, pharmacokinetics, radiation dosimetry, and acute toxicity of [(18)F]AmBF(3)-TATE were assessed with good laboratory practice (GLP) standards. METHODS: ICR mice were intravenously administered 0.8–2.0 MBq of [(18)F]AmBF(3)-TATE, with one group pre-injected with 100 μg of [(19)F]AmBF(3)-TATE 30 min before radiopharmaceutical administration to assess uptake specificity. The mice were euthanized at 0.5, 1, 2, or 4 h post-injection (p.i.). Blood and tissues were collected, weighed, and counted on a gamma counter to determine percentage injected dose per gram (%ID/g). Dosimetry was calculated based on biodistribution data using the mouse and human phantoms included in OLINDA. Acute toxicity was assessed in Sprague-Dawley rats at the dose of 0.742 mg/kg [(19)F]AmBF(3)-TATE, with a 14-day observation/recovery period. Blood chemistry parameters, gross, and histopathology were evaluated. Body weight change and food consumption were monitored. The production of [(18)F]AmBF(3)-TATE was automated on a Trasis AllinOne synthesis module. RESULTS: [(18)F]AmBF(3)-TATE was cleared through the renal and hepatobiliary pathway. At 1 h p.i., the pancreas (F, 15.7 ± 3.72 and M 14.3 ± 1.61 %ID/g), stomach (F, 15.3 ± 3.63 and M, 19.0 ± 3.49 %ID/g), and lungs (F, 9.26 ± 2.24 and M, 6.17 ± 6.04 %ID/g) were the organs with the highest specific uptake. Pre-injection with [(19)F]AmBF(3)-TATE significantly reduced pancreatic uptake (F, 0.13 ± 0.03 and M, 0.18 ± 0.09 %ID/g) at 1 h p.i. For dosimetry extrapolated to the average adult human, the bladder (0.027–0.030 mGy/MBq), pancreas (0.018–0.028 mGy/MBq), and lungs (0.006–0.013 mGy/MBq) are expected to receive the highest doses. No test-item related effects were observed upon evaluation of clinical observations, body weights, food consumption, clinical pathology, gross pathology, and histopathology for acute toxicity. [(18)F]AmBF(3)-TATE was produced at activity yields of 15.6 ± 4.59 GBq, average molar activity of 435 ± 162 GBq/μmol, and radiochemical purity of 98.0 ± 1.73% with the automated synthesizer. CONCLUSION: [(18)F]AmBF(3)-TATE binds specifically to SSTR2. At 1000× clinical dose, [(19)F]AmBF(3)-TATE was well tolerated with no treatment-related adverse effects. Springer Berlin Heidelberg 2020-03-19 /pmc/articles/PMC7080905/ /pubmed/32189151 http://dx.doi.org/10.1186/s13550-020-0611-9 Text en © The Author(s). 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Research Lau, Joseph Pan, Jinhe Rousseau, Etienne Uribe, Carlos F. Seelam, Sudhakara Reddy Sutherland, Brent W. Perrin, David M. Lin, Kuo-Shyan Bénard, François Pharmacokinetics, radiation dosimetry, acute toxicity and automated synthesis of [(18)F]AmBF(3)-TATE |
title | Pharmacokinetics, radiation dosimetry, acute toxicity and automated synthesis of [(18)F]AmBF(3)-TATE |
title_full | Pharmacokinetics, radiation dosimetry, acute toxicity and automated synthesis of [(18)F]AmBF(3)-TATE |
title_fullStr | Pharmacokinetics, radiation dosimetry, acute toxicity and automated synthesis of [(18)F]AmBF(3)-TATE |
title_full_unstemmed | Pharmacokinetics, radiation dosimetry, acute toxicity and automated synthesis of [(18)F]AmBF(3)-TATE |
title_short | Pharmacokinetics, radiation dosimetry, acute toxicity and automated synthesis of [(18)F]AmBF(3)-TATE |
title_sort | pharmacokinetics, radiation dosimetry, acute toxicity and automated synthesis of [(18)f]ambf(3)-tate |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080905/ https://www.ncbi.nlm.nih.gov/pubmed/32189151 http://dx.doi.org/10.1186/s13550-020-0611-9 |
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