⁶⁸Ga-NOTA-UBI-29-41 as a PET Tracer for Detection of Bacterial Infection

Abstract

The cationic peptide 68 Ga-NOTA-UBI-29-41 was synthesized and characterized. Biodistribution and PET/CT examinations were performed for evaluation of its biologic behavior. Differentiation of infection from sterile inflammation was investigated using microbiology methods at the sites of bacterial infections. Methods: Labeling of UBI-29-41 conjugated with NOTA with 68 Ga was optimized at 20°C-100°C and pH 3.5-5.5. Radiochemical purity, stability up to 260 min, and binding to serum proteins were determined. In vitro binding to Staphylococcus aureus was evaluated from 9.14 · 10 7 to 1.17 · 10 10 cfu/mL. Of 3 groups of Mus musculus Swiss male mice, the first was inoculated intramuscularly with 1.2 · 10 8 cfu of S. aureus to provoke infection, and the second, with 1.2 · 10 8 cfu of heat shock-treated S. aureus to generate sterile inflammation. The third mouse was not treated and served as a control. After 24 h, 68 Ga-NOTA-UBI-29-41 was administrated intravenously, and biodistribution was performed at 30, 60, and 120 min. PET/CT dynamic studies (120 min) were acquired. Sinograms were reconstructed using 3D maximum-likelihood expectation maximization and analyzed with software. Infected or inflamed muscles were dissected, homogenized, and cultured in tryptic soy agar medium. Recovered S. aureus was calculated as cfu/g. Results: 68 Ga-NOTA-UBI-29-41 showed high renal excretion (83.2% ± 7.3%) of injected dose and rapid blood clearance. More than 95% was bound in vitro to 5 · 10 9 cfu/mL. A significantly higher (P , 0.05) accumulation of 68 Ga-NOTA-UBI-29-41 was observed at sites of S. aureus inoculation in infected mice (ratio of target to nontarget, 5.0 at 60 min and 4.1 at 120 min) compared with animals with inflammation (ratio of target to nontarget, 1.6 at 60 min and 1.2 at 120 min). Conclusion: The difference in uptake of 68 Ga-NOTA-UBI-29-41 in the infected muscles compared with the inflamed muscles was clearly observed in the PET/CT images and positively correlated with the degree of infection.

Evaluating Ga-68 Peptide Conjugates for Targeting VPAC Receptors: Stability and Pharmacokinetics

“…Mirzaei et al have used ITLC method to test stability of [ 68 Ga]ECC using fresh human serum [35]. Many studies have used either HPLC or TLC method to test the in vivo and ex vivo stability [36–41]. We have precipitated plasma proteins using chloroform/ethanol (4/1) and analyzed the supernatant by HPLC.…”

A Systematic Approach for Developing Bacteria-Specific Imaging Tracers

“…For example, 99m Tc-ciprofloxacin was evaluated in a clinical study for diagnosing infections (12), but follow-up studies demonstrated nonspecific binding, and an inability to differentiate infection from sterile inflammation (13,14). Radiolabeled peptides have shown promise in preclinical models (15,16), but lack mechanistic binding or uptake, which could limit generalizability (17). In addition, 124 I-FIAU, a nucleoside analog substrate for thymidine kinase, has been described as a γ-herpesvirus and bacteria-selective tracer (18).…”

Specific Imaging of Bacterial Infection Using 6″-18F-Fluoromaltotriose: A Second-Generation PET Tracer Targeting the Maltodextrin Transporter in Bacteria

“…Recent years have seen the development of several PET tracers, including 68 Ga-ubiquicidin and 29-deoxy-29-fluoro-1bD-arabinofuranosyl-5-124 I-iodouracil ( 124 I-FIAU) (9)(10)(11). Of these, 68 Ga-ubiquicidin has shown promise in preclinical studies (11), but further evaluation in multicenter clinical trials is warranted (11,12). Other tracers including 18 F-fluorodeoxysorbitol have been shown to detect only a specific class of bacteria (e.g., gram-negative Enterobacteriaceae) (13).…”