Purpose: Vitamin B12 (cyanocobalamin, Cbl) is accumulated by rapidly replicating prokaryotic and eukaryotic cells. We investigated the potential of a Tc-99m labelled Cbl derivative ([99mTc]PAMA(4)-Cbl) for targeting infections caused by Escherichia coli and Staphylococcus aureus. In vitro binding assays were followed by biodistribution studies in a mouse model of foreign body infection. Procedures: E. coli (ATCC 25922) and S. aureus (ATCC 43335) were used as test strains. [57Co]Cbl, [67Ga]citrate and [99mTc]DTPA served as reference compounds. The in vitro competitive binding of [57Co]Cbl or [99mTc]PAMA(4)-Cbl, and unlabeled Cbl, to viable or killed bacteria, was evaluated at 37 and 4 °C. A cage mouse model of infection was used for biodistribution of intravenous [57Co]Cbl and [99mTc]PAMA(4)-Cbl in cage and dissected tissues of infected and non-infected mice. Results: Maximum binding (mean ± SD) of [57Co]Cbl to viable E. coli was 81.7 ± 2.6 % and to S. aureus 34.0 ± 6.7 %, at 37 °C; no binding occurred to heat-killed bacteria. Binding to both test strains was displaced by 100- to 1000-fold excess of unlabeled Cbl. The in vitro binding of [99mTc]PAMA(4)-Cbl was 100-fold and 3-fold lower than the one of [57Co]Cbl for E. coli and S. aureus, respectively. In vivo, [99mTc]PAMA(4)-Cbl showed peak percentage of injected dose (% ID) values between 1.33 and 2.3, at 30 min post-injection (p.i.). Significantly higher retention occurred in cage fluids infected with S. aureus at 4 h and with E. coli at 8 h p.i. than in non-infected animals. Accumulation into infected cages was also higher than the one of [99mTc]DTPA, which showed similar biodistribution in infected and sterile mice. [57Co]Cbl gradually accumulated in cages with peaks % ID between 3.58 and 4.83 % achieved from 24 to 48 h. Discrimination for infection occurred only in E. coli-infected mice, at 72 h p.i. [67Ga]citrate, which showed a gradual accumulation into cage fluids during 12 h, was discriminative for infection from 48 to 72 h p.i. (P < 0.05). Conclusion: Cbl displayed rapid and specific in vitro binding to test strains. [99mTc]PAMA(4)-Cbl was rapidly cleared from most tissues and discriminated between sterile and infected cages, being a promising candidate for imaging infections in humans.
|Titolo:||Evaluation of a Novel Tc-99m Labelled Vitamin B12 Derivative for Targeting Escherichia coli and Staphylococcus aureus In Vitro and in an Experimental Foreign-Body Infection Model|
GALLI, FILIPPO [Supervision]
SIGNORE, Alberto [Supervision] (Corresponding author)
|Data di pubblicazione:||2015|
|Citazione:||Evaluation of a Novel Tc-99m Labelled Vitamin B12 Derivative for Targeting Escherichia coli and Staphylococcus aureus In Vitro and in an Experimental Foreign-Body Infection Model / D., Baldoni; R., Waibel; P., Bläuenstein; Galli, Filippo; V., Iodice; Signore, Alberto; R., Schibli; A., Trampuz. - In: MOLECULAR IMAGING AND BIOLOGY. - ISSN 1536-1632. - STAMPA. - 17:6(2015), pp. 829-837.|
|Appare nella tipologia:||01a Articolo in rivista|