Cargando…
DOTA-ZOL: A Promising Tool in Diagnosis and Palliative Therapy of Bone Metastasis—Challenges and Critical Points in Implementation into Clinical Routine
The novel compound 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-ZOL (DOTA-conjugated zoledronic acid) is a promising candidate for the diagnosis and therapy of bone metastasis. The combination of the published methodology for this bisphosphonate with pharmaceutical and regulatory...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412164/ https://www.ncbi.nlm.nih.gov/pubmed/32629930 http://dx.doi.org/10.3390/molecules25132988 |
_version_ | 1783568545100070912 |
---|---|
author | Meisenheimer, Michael Kürpig, Stefan Essler, Markus Eppard, Elisabeth |
author_facet | Meisenheimer, Michael Kürpig, Stefan Essler, Markus Eppard, Elisabeth |
author_sort | Meisenheimer, Michael |
collection | PubMed |
description | The novel compound 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-ZOL (DOTA-conjugated zoledronic acid) is a promising candidate for the diagnosis and therapy of bone metastasis. The combination of the published methodology for this bisphosphonate with pharmaceutical and regulatory requirements turned out to be unexpectedly challenging. The scope of this work is the presentation and discussion of problems encountered during this process. Briefly, the radiolabelling process and purification, as well as the quality control published, did not meet the expectations. The constant effort setting up an automated radiolabelling procedure resulted in (a) an enhanced manual method using coated glass reactors, (b) a combination of three different reliable radio thin-layer chromatography (TLC) methods instead of the published and (c) a preliminary radio high-pressure liquid chromatography (HPLC) method for identification of the compound. Additionally, an automated radiolabelling process was developed, but it requires further improvement, e.g., in terms of a reactor vessel or purification of the crude product. The published purification method was found to be unsuitable for clinical routine, and an intense screening did not lead to a satisfactory result; here, more research is necessary. To sum up, implementation of DOTA-ZOL was possible but revealed a lot of critical points, of which not all could be resolved completely yet. |
format | Online Article Text |
id | pubmed-7412164 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74121642020-08-17 DOTA-ZOL: A Promising Tool in Diagnosis and Palliative Therapy of Bone Metastasis—Challenges and Critical Points in Implementation into Clinical Routine Meisenheimer, Michael Kürpig, Stefan Essler, Markus Eppard, Elisabeth Molecules Article The novel compound 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-ZOL (DOTA-conjugated zoledronic acid) is a promising candidate for the diagnosis and therapy of bone metastasis. The combination of the published methodology for this bisphosphonate with pharmaceutical and regulatory requirements turned out to be unexpectedly challenging. The scope of this work is the presentation and discussion of problems encountered during this process. Briefly, the radiolabelling process and purification, as well as the quality control published, did not meet the expectations. The constant effort setting up an automated radiolabelling procedure resulted in (a) an enhanced manual method using coated glass reactors, (b) a combination of three different reliable radio thin-layer chromatography (TLC) methods instead of the published and (c) a preliminary radio high-pressure liquid chromatography (HPLC) method for identification of the compound. Additionally, an automated radiolabelling process was developed, but it requires further improvement, e.g., in terms of a reactor vessel or purification of the crude product. The published purification method was found to be unsuitable for clinical routine, and an intense screening did not lead to a satisfactory result; here, more research is necessary. To sum up, implementation of DOTA-ZOL was possible but revealed a lot of critical points, of which not all could be resolved completely yet. MDPI 2020-06-30 /pmc/articles/PMC7412164/ /pubmed/32629930 http://dx.doi.org/10.3390/molecules25132988 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Meisenheimer, Michael Kürpig, Stefan Essler, Markus Eppard, Elisabeth DOTA-ZOL: A Promising Tool in Diagnosis and Palliative Therapy of Bone Metastasis—Challenges and Critical Points in Implementation into Clinical Routine |
title | DOTA-ZOL: A Promising Tool in Diagnosis and Palliative Therapy of Bone Metastasis—Challenges and Critical Points in Implementation into Clinical Routine |
title_full | DOTA-ZOL: A Promising Tool in Diagnosis and Palliative Therapy of Bone Metastasis—Challenges and Critical Points in Implementation into Clinical Routine |
title_fullStr | DOTA-ZOL: A Promising Tool in Diagnosis and Palliative Therapy of Bone Metastasis—Challenges and Critical Points in Implementation into Clinical Routine |
title_full_unstemmed | DOTA-ZOL: A Promising Tool in Diagnosis and Palliative Therapy of Bone Metastasis—Challenges and Critical Points in Implementation into Clinical Routine |
title_short | DOTA-ZOL: A Promising Tool in Diagnosis and Palliative Therapy of Bone Metastasis—Challenges and Critical Points in Implementation into Clinical Routine |
title_sort | dota-zol: a promising tool in diagnosis and palliative therapy of bone metastasis—challenges and critical points in implementation into clinical routine |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412164/ https://www.ncbi.nlm.nih.gov/pubmed/32629930 http://dx.doi.org/10.3390/molecules25132988 |
work_keys_str_mv | AT meisenheimermichael dotazolapromisingtoolindiagnosisandpalliativetherapyofbonemetastasischallengesandcriticalpointsinimplementationintoclinicalroutine AT kurpigstefan dotazolapromisingtoolindiagnosisandpalliativetherapyofbonemetastasischallengesandcriticalpointsinimplementationintoclinicalroutine AT esslermarkus dotazolapromisingtoolindiagnosisandpalliativetherapyofbonemetastasischallengesandcriticalpointsinimplementationintoclinicalroutine AT eppardelisabeth dotazolapromisingtoolindiagnosisandpalliativetherapyofbonemetastasischallengesandcriticalpointsinimplementationintoclinicalroutine |