dc.contributor.author |
Ebenhan, Thomas
|
|
dc.contributor.author |
Zeevaart, Jan Rijn
|
|
dc.contributor.author |
Venter, Jacobus D.
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|
dc.contributor.author |
Govender, Thavendran
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|
dc.contributor.author |
Kruger, Gert H.
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|
dc.contributor.author |
Jarvis, Neil V.
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|
dc.contributor.author |
Sathekge, Mike Machaba
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dc.date.accessioned |
2014-08-19T08:47:02Z |
|
dc.date.available |
2014-08-19T08:47:02Z |
|
dc.date.issued |
2014-02 |
|
dc.description.abstract |
Antimicrobial peptides such as ubiquicidin (UBI) are believed to differentiate between mammalian and bacterial or fungal cells. (99m)Tc-UBI29-41 was previously tested for detecting infection in humans using SPECT. For the present study, the UBI fragment UBI29-41 (TGRAKRRMQYNRR) was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA), radiolabeled with (68)Ga, and investigated in a rabbit infection model.
METHODS : (68)Ga was obtained from a 1.85-GBq (68)Ge/(68)Ga generator. New Zealand White rabbits were anesthetized with ketamine/medetomidine before tracer administration and placed in a clinical PET/CT scanner. (68)Ga-1,4,7-triazacyclononane-1,4,7-triacetic-acid-ubiquicidin29-41 ((68)Ga-NOTA-UBI29-41) was formulated in saline solution, and 101 ± 41 MBq were administered intravenously. The tracer distribution was studied by PET/CT imaging in animals (a) that were healthy, (b) bearing muscular Staphylococcus aureus infections and turpentine oil-induced muscular inflammations, and (c) bearing ovalbumin-induced lung inflammations. Static PET/CT imaging was performed at different time intervals up to 120 min after injection. For calculation of target-to-nontarget ratios, standardized uptake values were normalized against healthy thigh muscle, representing nontargeted tissue.
RESULTS : PET/CT images of healthy animals showed predominant distribution in the kidneys, liver, and bladder; heart and spleen showed moderate, declining uptake, only. The biologic half-life in blood was 29 min. Urinary accumulation of (68)Ga-NOTA-UBI29-41 peaked at 3.8 ± 0.91 percentage injected dose per gram (%ID) at 120 min, and 88 ± 5.2 %ID was recovered in total urine. (68)Ga-NOTA-UBI29-41 imaging in (b) selectively visualized the muscular infection site and was differentiated from sterile inflammatory processes. Standardized uptake value ratios for muscles (infected/inflamed) were 2.9 ± 0.93, 2.9 ± 0.50, 3.5 ± 0.86, and 3.8 ± 0.90 at 5, 30, 60, and 90 min after injection, respectively. Rabbit lungs with asthma showed insignificant uptake.
CONCLUSION : (68)Ga-NOTA-UBI29-41 was strongly localized in bacteria-infected areas and minimally detected in a sterile inflammation area in rabbit muscles. The findings propose this compound to be an excellent first-line PET/CT tracer to allow the distinguishing of infection from inflammation. |
en_US |
dc.description.librarian |
hb2014 |
en_US |
dc.description.uri |
http://jnm.snmjournals.org/ |
en_US |
dc.identifier.citation |
Ebenhan, T, Zeevaart, JR, Venter, JD, Govender, T, Kruger, GH, Jarvis, NV & Sathekge, MM 2014, 'Preclinical evaluation of 68Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-ubiquicidin as a radioligand for PET infection imaging', Journal of Nuclear Medicine, vol. 55, no. 2, pp. 308-314. |
en_US |
dc.identifier.issn |
0161-5505 (print) |
|
dc.identifier.issn |
1535-5667 (online) |
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dc.identifier.other |
10.2967/jnumed.113.128397 |
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dc.identifier.uri |
http://hdl.handle.net/2263/41441 |
|
dc.language.iso |
en |
en_US |
dc.publisher |
Society of Nuclear Medicine |
en_US |
dc.rights |
© 2014 Society of Nuclear Medicine and Molecular Imaging. This research was originally published in Journal of Nuclear Medicine, Preclinical evaluation of 68Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-ubiquicidin as a radioligand for PET infection imaging, Ebenhan, T, Zeevaart, JR, Venter, JD, Govender, T, Kruger, GH, Jarvis, NV & Sathekge, MM, vol. 55, no.2, pp. 308-314, doi : 10.2967/jnumed.113.128397. |
en_US |
dc.subject |
68Ga labeling |
en_US |
dc.subject |
PET/CT |
en_US |
dc.subject |
UBI29-41 |
en_US |
dc.subject |
Infection |
en_US |
dc.subject |
Ubiquicidin |
en_US |
dc.subject |
Computerized tomography (CT) |
|
dc.subject |
Positron emission tomography (PET) |
|
dc.title |
Preclinical evaluation of 68Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-ubiquicidin as a radioligand for PET infection imaging |
en_US |
dc.type |
Postprint Article |
en_US |