In vitro and in vivo assessment of 99mTc-UBI specificity for bacteria

Ferro-Flores, Guillermina; Murphy, Consuelo Arteaga de; Pedraza-López, Martha; Meléndez‐Alafort, Laura; Zhang, Yumin; Rusckowski, Mary; Hnatowich, Donald J.

doi:10.1016/s0969-8051(03)00054-4

Cited by 65 publications

(37 citation statements)

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“…The UBI29-41 peptide fragment proved to be more difficult to synthesize than the UBI30-41 peptide, requiring multiple attempts to produce satisfactory yields of the desired peptide. This was unexpected as previously published reports do not mention difficulties in the synthesis of UBI29-41 [5,6,22]. Since the syntheses were initiated at the Cterminus, it could be suggested that the problem may have occurred on addition of the last amino acid, threonine.…”

Section: Discussionmentioning

confidence: 85%

Peptide synthesis, characterization and 68Ga-radiolabeling of NOTA-conjugated ubiquicidin fragments for prospective infection imaging with PET/CT

Ebenhan

Chadwick

Sathekge

et al. 2014

Nuclear Medicine and Biology

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Section: Discussionmentioning

confidence: 85%

Peptide synthesis, characterization and 68Ga-radiolabeling of NOTA-conjugated ubiquicidin fragments for prospective infection imaging with PET/CT

Ebenhan

Chadwick

Sathekge

et al. 2014

Nuclear Medicine and Biology

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“…One of these chelators is 1,4,7-triazacyclononane-triacetic acid (NOTA), which has a high affinity for 68 Ga and therefore conjugates with peptides to functionalize these toward radiolabeling for prospective PET imaging (14). Preclinical publications (13,15,16) (17,18). Key to this approach is that this peptide accumulates at infection sites but not in sterile inflammatory lesions.…”

mentioning

confidence: 99%

Preclinical Evaluation of ⁶⁸Ga-Labeled 1,4,7-Triazacyclononane-1,4,7-Triacetic Acid-Ubiquicidin as a Radioligand for PET Infection Imaging

et al. 2014

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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 6 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 oilinduced 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 6 0.91 percentage injected dose per gram (%ID) at 120 min, and 88 6 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 6 0.93, 2.9 6 0.50, 3.5 6 0.86, and 3.8 6 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.

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“…The in vitro binding of 99m Tc-UBI 29-41 has been reported to be 34.3% 6 3.0% (5). Corresponding values were approximately 15% for 18 F-UBI 29-41 (8) and 37%-57% for 18 F-UBI 28-41 (Sijtse Zijlstra, unpublished data, 2006) indicating that the 18 F-labeled UBI derivatives have a potential similar to that of 99m Tc-UBI 29-41 for imaging bacterial infections.…”

Section: Discussionmentioning

confidence: 99%

“…99m Tc-UBI 29-41 binds to the negatively charged groups present on the bacterial cell envelope by electrostatic interaction, and there is some evidence that a specific mechanism is responsible for intrabacterial 99m Tc-UBI 29-41 accumulation (5). 99m Tc-UBI has been shown to accumulate at sites of muscular infections in mice and rabbits but not in inflamed aseptic muscular abscesses induced by lipopolysaccharides (6).…”

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confidence: 99%

Comparison of ^99mTc- and ¹⁸F-Ubiquicidin Autoradiography to Anti–Staphylococcus aureus Immunofluorescence in Rat Muscle Abscesses

Salber

Gunawan²,

Langen³

et al. 2008

J Nucl Med

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99m Tc-ubiquicidin (UBI) 29-41 is under clinical evaluation for discrimination between bacterial infection and unspecific inflammation. We compared the distribution of 99m Tc-UBI 29-41, the potential PET tracers 18 F-UBI 29-41 and 18 F-UBI 28-41, and 3 H-deoxyglucose (DG) in rat muscle abscesses to that of antiStaphylococcus aureus immunofluorescent imaging. Methods: Calf abscesses were induced in 15 CDF-Fischer rats after inoculation of Staphylococcus aureus. One to 6 d later, either 18 F-UBI 29-41 and 3 H-DG (n 5 5) or 18 F-UBI 28-41 and 3 H-DG (n 5 6) or 99m Tc-UBI 29-41 and 3 H-DG (n 5 4) were injected simultaneously. Dual-tracer autoradiography of the abscess area was compared with the distribution of bacteria and macrophages. Results: The UBI derivates exhibited increased uptake in the abscess area that partly matched 3 H-DG uptake and macrophage infiltration but showed no congruity with areas that were highly positive for bacteria. Conclusion: A specific binding of UBI derivatives to Staphylococcus aureus in vivo could not be confirmed in this study.

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In vitro and in vivo assessment of 99mTc-UBI specificity for bacteria

Cited by 65 publications

References 10 publications

Peptide synthesis, characterization and 68Ga-radiolabeling of NOTA-conjugated ubiquicidin fragments for prospective infection imaging with PET/CT

Peptide synthesis, characterization and 68Ga-radiolabeling of NOTA-conjugated ubiquicidin fragments for prospective infection imaging with PET/CT

Preclinical Evaluation of ⁶⁸Ga-Labeled 1,4,7-Triazacyclononane-1,4,7-Triacetic Acid-Ubiquicidin as a Radioligand for PET Infection Imaging

Comparison of ^99mTc- and ¹⁸F-Ubiquicidin Autoradiography to Anti–Staphylococcus aureus Immunofluorescence in Rat Muscle Abscesses

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In vitro and in vivo assessment of 99mTc-UBI specificity for bacteria

Cited by 65 publications

References 10 publications

Peptide synthesis, characterization and 68Ga-radiolabeling of NOTA-conjugated ubiquicidin fragments for prospective infection imaging with PET/CT

Peptide synthesis, characterization and 68Ga-radiolabeling of NOTA-conjugated ubiquicidin fragments for prospective infection imaging with PET/CT

Preclinical Evaluation of 68Ga-Labeled 1,4,7-Triazacyclononane-1,4,7-Triacetic Acid-Ubiquicidin as a Radioligand for PET Infection Imaging

Comparison of 99mTc- and 18F-Ubiquicidin Autoradiography to Anti–Staphylococcus aureus Immunofluorescence in Rat Muscle Abscesses

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Preclinical Evaluation of ⁶⁸Ga-Labeled 1,4,7-Triazacyclononane-1,4,7-Triacetic Acid-Ubiquicidin as a Radioligand for PET Infection Imaging

Comparison of ^99mTc- and ¹⁸F-Ubiquicidin Autoradiography to Anti–Staphylococcus aureus Immunofluorescence in Rat Muscle Abscesses