Biokinetics of 99mTc-UBI 29-41 in humans
Introduction
An ideal radiopharmaceutical for infection imaging should satisfy the following criteria: high and specific uptake at the site of infection; rapid detection of infection; rapid background clearance; minimal accumulation in non-target tissues; low toxicity and zero immune response and in particular, an ability to differentiate infection from sterile inflammation [1].
Recently, antimicrobial peptides have been proposed as new 99mTc agents to distinguish bacterial infections from sterile inflammatory processes [2], and also, to monitor the efficacy of antibiotic therapy [1], [2]. Ubiquicidin 29-41 (UBI) is a fragment of the cationic antimicrobial peptide that is present in various species including humans. Its amino acid sequence is Thr-Gly-Arg-Ala-Lys-Arg-Arg-Met-Gln-Tyr-Asn-Arg-Arg (MW 1.69 kDa). After 99mTc labeling through probably the amine groups of Arg7 and Lys, UBI showed radiochemical purities over 97%, high stability in human serum and in cysteine solutions [3]. In vitro test demonstrated that 99mTc-UBI was specifically bound to bacteria and fungi and that it is accumulated at sites of infection showing an average infection/inflammation ratio of 2.08 ± 0.49 in experimental animals [4], [5]. These biodistribution studies have demonstrated a fast renal clearance with minimal hepatobiliary excretion in mice [3], [4], [5].
The aim of this study was to establish a 99mTc-UBI biokinetic model and evaluate its feasibility as an infection imaging agent in humans using 67Ga-citrate as a control.
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Materials and methods
Ubiquicidin 29-41 fragment peptide (UBI) was synthesized and characterized at the Leiden University Medical Center; The Netherlands. All the other reagents were analytical grade and were used without further purification. The 99mTc-pertechnetate was obtained from a GETEC 99Mo/99mTc generator (ININ). 67Ga-citrate was purchased at a radiochemical concentration of 37 MBq/mL (Syncor-Mexico).
Six children between 2 and 15 years old with suspected bone infection in different areas of the skeleton were
Results
None of the children reported any adverse reaction as nausea, dysnea, bronchospasm, decreased blood pressure, itching, flushing, hives, chills, coughing, bradycardia, muscle cramps or dizziness after the radiopharmaceuticals were administered.
The average radiochemical purity of 99mTc-UBI, determined by Sep-Pak cartridge and reverse phase HPLC, was in all the cases over 97%.
99mTc-UBI showed a fast renal clearance (Fig. 1, Fig. 2). Two hours after administration the percentage of the injected
Discussion
For reliable biokinetic studies, it is essential to obtain valid data from biological samples and from images. However, the study of new methods to obtain “absolute activities” from scintigraphic images continues [7]. An accurate estimation of the activity in any organ from the measured counting rate requires correction for the system calibration factor (cpm/MBq), for attenuation, scatter, background activity, organ and patient thickness and physical decay of the radionuclide used. In this
Acknowledgements
This work was partially supported by CONACyT (Consejo Nacional de Ciencia y Tecnología) and UAEM (Universidad Autónoma del Estado de México).
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