Synthesis, 68Ga-radiolabeling, and preliminary in vivo assessment of a depsipeptide-derived compound as a potential PET/CT infection imaging agent
Date
2015Author
Mokaleng, Botshelo B.
Zeevaart, Jan R.
Ebenhan, Thomas
Ramesh, Suhas
Govender, Thavendran
Metadata
Show full item recordAbstract
Noninvasive imaging is a powerful tool for early diagnosis and monitoring of various disease processes, such as infections. An
alarming shortage of infection-selective radiopharmaceuticals exists for overcoming the diagnostic limitations with unspecific
tracers such as 67/68Ga-citrate or 18F-FDG. We report here TBIA101, an antimicrobial peptide derivative that was conjugated to
DOTA and radiolabeled with 68Ga for a subsequent in vitro assessment and in vivo infection imaging using Escherichia coli-bearing
mice by targeting bacterial lipopolysaccharides with PET/CT. Following DOTA-conjugation, the compound was verified for its
cytotoxic and bacterial binding behaviour and compound stability, followed by 68Gallium-radiolabeling. 𝜇PET/CT using 68Ga-
DOTA-TBIA101 was employed to detect muscular E. coli-infection in BALB/c mice, as warranted by the in vitro results. 68Ga-
DOTA-TBIA101-PET detected E. coli-infected muscle tissue (SUV = 1.3–2.4) > noninfected thighs (𝑃 = 0.322) > forearm muscles
(𝑃 = 0.092) > background (𝑃 = 0.021) in the same animal. Normalization of the infected thigh muscle to reference tissue showed
a ratio of 3.0 ± 0.8 and a ratio of 2.3 ± 0.6 compared to the identical healthy tissue. The majority of the activity was cleared by
renal excretion.The latter findings warrant further preclinical imaging studies of greater depth, as the DOTA-conjugation did not
compromise the TBIA101’s capacity as targeting vector
URI
http://hdl.handle.net/10394/18350http://www.hindawi.com/journals/bmri/2015/284354/
https://doi.org/10.1155/2015/284354
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- Faculty of Health Sciences [2377]