68Ga-labeled PET tracers for targeting tumor hypoxia : Role of bifunctional chelators on pharmacokinetics
Copyright © 2021 Elsevier Inc. All rights reserved..
INTRODUCTION: By virtue of their oxygen dependant accumulation in hypoxic cells, radiolabeled nitroimidazole analogues have been widely used for detecting tumor hypoxia. Present study evaluates two 2-nitroimidazole (2-NIM) based 68Ga-labeled radiotracers, [68Ga]Ga-DOTAGA-2-NIM and [68Ga]Ga-NODAGA-2-NIM, for hypoxia targeting applications.
METHODS: Bifunctional chelating agents suitable for radiolabeling with 68Ga, viz. 1,4,7,10-tetraazacyclododececane,1-(glutaric acid)-4,7,10-triacetic acid (DOTAGA) and 1,4,7-triazacyclododececane,1-(glutaric acid)-4,7-diacetic acid (NODAGA), were coupled to appropriately modified 2-nitroimidazole to obtain 2-NIM-DOTAGA and 2-NIM-NODAGA, respectively. These ligands were radiolabeled using [68Ga]GaCl3 obtained from a commercial 68Ge/68Ga-generator to obtain corresponding 68Ga-complexes. Both the radiotracers were tested for their hypoxia selectivity in CHO cells under hypoxic and normoxic conditions. Biodistribution studies in fibrosarcoma tumor bearing Swiss mice were carried out to evaluate the radiotracer in vivo.
RESULTS: The 68Ga complexes of 2-NIM-DOTAGA and 2-NIM-NODAGA could be prepared in ~82% and ~90% yield, respectively. In vitro studies of the complexes in CHO cells showed significant accumulation of [68Ga]Ga-NODAGA-2-NIM complex under hypoxic conditions with hypoxic to normoxic ratio of 2.88 ± 0.36 at 180 min post incubation. The [68Ga]Ga-DOTAGA-2-NIM complex also showed hypoxia selectivity albeit to a lesser extent. Biodistribution studies of the complexes in Swiss mice bearing fibrosarcoma tumor showed significant tumor uptake by both radiolabeled complexes. [68Ga]Ga-NODAGA-2-NIM showed a more favorable pharmacokinetics with respect to [68Ga]Ga-DOTAGA-2-NIM.
CONCLUSION: The nitroimidazole radiotracer with NODAGA chelator displayed more favorable pharmacokinetics and good hypoxia selectivity, making it a promising candidate for further investigation. The present study also provides an insight into the possible role of bifunctional chelator on overall pharmacokinetics of small molecule radiotracers.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2021 |
---|---|
Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:96-97 |
---|---|
Enthalten in: |
Nuclear medicine and biology - 96-97(2021) vom: 15. Mai, Seite 61-67 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Mittal, Sweety [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 16.12.2021 Date Revised 16.12.2021 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1016/j.nucmedbio.2021.03.004 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM323936024 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM323936024 | ||
003 | DE-627 | ||
005 | 20231225185239.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2021 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.nucmedbio.2021.03.004 |2 doi | |
028 | 5 | 2 | |a pubmed24n1079.xml |
035 | |a (DE-627)NLM323936024 | ||
035 | |a (NLM)33838524 | ||
035 | |a (PII)S0969-8051(21)00047-0 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Mittal, Sweety |e verfasserin |4 aut | |
245 | 1 | 0 | |a 68Ga-labeled PET tracers for targeting tumor hypoxia |b Role of bifunctional chelators on pharmacokinetics |
264 | 1 | |c 2021 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 16.12.2021 | ||
500 | |a Date Revised 16.12.2021 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2021 Elsevier Inc. All rights reserved. | ||
520 | |a INTRODUCTION: By virtue of their oxygen dependant accumulation in hypoxic cells, radiolabeled nitroimidazole analogues have been widely used for detecting tumor hypoxia. Present study evaluates two 2-nitroimidazole (2-NIM) based 68Ga-labeled radiotracers, [68Ga]Ga-DOTAGA-2-NIM and [68Ga]Ga-NODAGA-2-NIM, for hypoxia targeting applications | ||
520 | |a METHODS: Bifunctional chelating agents suitable for radiolabeling with 68Ga, viz. 1,4,7,10-tetraazacyclododececane,1-(glutaric acid)-4,7,10-triacetic acid (DOTAGA) and 1,4,7-triazacyclododececane,1-(glutaric acid)-4,7-diacetic acid (NODAGA), were coupled to appropriately modified 2-nitroimidazole to obtain 2-NIM-DOTAGA and 2-NIM-NODAGA, respectively. These ligands were radiolabeled using [68Ga]GaCl3 obtained from a commercial 68Ge/68Ga-generator to obtain corresponding 68Ga-complexes. Both the radiotracers were tested for their hypoxia selectivity in CHO cells under hypoxic and normoxic conditions. Biodistribution studies in fibrosarcoma tumor bearing Swiss mice were carried out to evaluate the radiotracer in vivo | ||
520 | |a RESULTS: The 68Ga complexes of 2-NIM-DOTAGA and 2-NIM-NODAGA could be prepared in ~82% and ~90% yield, respectively. In vitro studies of the complexes in CHO cells showed significant accumulation of [68Ga]Ga-NODAGA-2-NIM complex under hypoxic conditions with hypoxic to normoxic ratio of 2.88 ± 0.36 at 180 min post incubation. The [68Ga]Ga-DOTAGA-2-NIM complex also showed hypoxia selectivity albeit to a lesser extent. Biodistribution studies of the complexes in Swiss mice bearing fibrosarcoma tumor showed significant tumor uptake by both radiolabeled complexes. [68Ga]Ga-NODAGA-2-NIM showed a more favorable pharmacokinetics with respect to [68Ga]Ga-DOTAGA-2-NIM | ||
520 | |a CONCLUSION: The nitroimidazole radiotracer with NODAGA chelator displayed more favorable pharmacokinetics and good hypoxia selectivity, making it a promising candidate for further investigation. The present study also provides an insight into the possible role of bifunctional chelator on overall pharmacokinetics of small molecule radiotracers | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a BFCA | |
650 | 4 | |a Bifunctional chelating agent | |
650 | 4 | |a Gallium-68 | |
650 | 4 | |a Nitroimidazole | |
650 | 4 | |a Positron emission tomography | |
650 | 4 | |a Tumor hypoxia | |
650 | 7 | |a 1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane |2 NLM | |
650 | 7 | |a Acetates |2 NLM | |
650 | 7 | |a Gallium Radioisotopes |2 NLM | |
650 | 7 | |a Heterocyclic Compounds, 1-Ring |2 NLM | |
700 | 1 | |a Sharma, Rohit |e verfasserin |4 aut | |
700 | 1 | |a Mallia, Madhava B |e verfasserin |4 aut | |
700 | 1 | |a Sarma, Haladhar Dev |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Nuclear medicine and biology |d 1996 |g 96-97(2021) vom: 15. Mai, Seite 61-67 |w (DE-627)NLM075154803 |x 1872-9614 |7 nnns |
773 | 1 | 8 | |g volume:96-97 |g year:2021 |g day:15 |g month:05 |g pages:61-67 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.nucmedbio.2021.03.004 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 96-97 |j 2021 |b 15 |c 05 |h 61-67 |