Authors:Andrzej Skoczowski, Anna Janeczko, Gábor Gullner, István Tóbias, Andrzej Kornas, and Balázs Barna
]. During hypersensitive response cell permeability rapidly increases as cell membranes break down. Pathogen infections not only affect defence reactions but also cause changes in photosynthesis [ 19 , 20 ]. Bonfig et al. [ 21 ] found that infection of
Authors:F. Yurt Lambrecht, O. Yilmaz, P. Unak, B. Seyitoglu, K. Durkan, S. Yolcular, and H. Baskin
The aim of this study was to evaluate 99mTc labeled human β-defensin-1 (HBD-1) for discrimination between bacterial infection and sterile inflammation. For this purpose,
HBD-1 was radiolabeled with 99mTc and its in vivo distribution was evaluated in inflamed rats with Staphylococcus aureus (S. aureus) and sterile inflamed rats with turpentine oil. After injection into inflamed and sterile inflamed rats, 99mTc-HBD-1 was rapidly removed from the circulation via the kidneys. Binding of 99mTc-HBD-1 to inflamed muscle (T/NT = 20 at 120 min) was two times higher than binding to sterile inflamed muscle (T/NT = 10
at 120 min) of rats. It was demonstrated that 99mTc-HBD-1 can be used to detect S. aureus inflammation in rats. However, the radiolabeled antimicrobial peptide showed only poor uptake in sterile inflammation with
turpentine oil in rats. As a result, 99mTc-HBD-1 can be useful for detection of bacterial inflammation.
Authors:F. Lambrecht, O. Yilmaz, E. Bayrak, G. Kocagozoglu, and K. Durkan
The aim of this study was to determine whether [131I]apigenin is a powerful and discrimination infection from inflammation for scintigraphic imaging. The study was carried out
in inflamed rats with Staphylococcus aureus (S. aureus) and sterile inflamed rats with turpentine oil. Biodistribution study of [131I]apigenin was performed in the rats. Apigenin was labeled with 131I by iodogen method. Obtained [131I]apigenin with high yield (98%) was injected i.v. to both group rats. The results were expressed as the percent uptake of
injected dose per gram of organ (%ID/g), the bacterial infected and sterile inflamed muscles. Binding of [131I]apigenin to the infected thigh muscle (target muscle = T) and normal thigh muscle (non-target muscle = NT) ratio (T/NT = 4.51
at 15 min) was higher than binding to bacterial inflamed muscle (T/NT = 2.25 at 15 min) of rats. [131I]apigenin showed good localization in both inflamed tissues. This uptake in the sterile inflamed tissue is higher than bacterial
infected tissue. [131I]apigenin might be useful for imaging of inflamed tissues. However, it is not discriminate sterile inflamed tissue from bacterial
Prompt localization of infection sites is essential for initiating appropriate therapeutic measures. There have been major
advances in the management of patients suffering from infective and/or inflammatory disorders as a result of introduction
of newer drugs with high sensitivity and specificity. Since the last decade, 99mTc-ciprofloxacin was used as a biologically active radiopharmaceutical to diagnose inflammation but it has some problems related
to radiochemical purity and stability. The aim of this study is to develop simple and easy formulation of cefoperazone (other
broad spectrum antimicrobial agent) with 99mTc a ready to use labeling kit for infection imaging. The optimum condition that gives high labeling yield of 99mTc-cefoperazone complex, 97.9%, was achieved by using 3 mg cefoperazone, 100 μg Sn(II), at pH 8 and 10-minute reaction time.
For in vivo binding of 99mTc-cefoperazone pharmacokinetic studies were carried in experimentally induced infection, in the left thigh, using Staphylococcus aureus in rats. Both thighs of the rats were dissected and counted and the ratio of bacterial infected thigh/contralateral thigh
was then evaluated. The time for maximum accumulation of 99mTc-cefoperazone at the site of infection (T/NT = 4.5) was 45-minute post intravenous injection, followed by gradual decline. So, 99mTc-cefoperazone complex is simple and stable preparation for infection imaging after 45-minute post injection.
Radiosynthesis of 99mTc-sitafloxacin (99mTc-STF) complex and its efficacy as a potential infection imaging agent was evaluated. Effect of sitafloxacin (STF) concentration,
sodium pertechnetate (Na99mTcO4), stannous chloride dihydrate (SnCl2·2H2O), and pH on the % radiochemical purity yield (RCP) of 99mTc-STF complex was studied. A stable 99mTc-STF complex up to 120 min with maximum %RCP yield was observed by mixing 2 mg of STF with 3 mCi of Na99mTcO4 and 150 μL of SnCl2·2H2O (1 μg/μL in 0.01 N HCl) at a pH 5.5. Artificially infected rats with Staphylococcus aureus were used for studying the biodistribution behavior of the 99mTc-STF complex. After 30 min of the intravenous (I.V.) administration of the 99mTc-STF complex, 7.50 ± 0.10% was absorbed in the infected thigh of the rats and the uptake gradually increased to 18.50 ± 0.20%
within 90 min. Rabbits with artificially induced infection were used for evaluating the scintigraphic accuracy. Higher uptake
in the infected thigh was observed after 2 h of I.V. administration of the 99mTc-STF complex. Target to non-target organ ratio of the % absorbed dose incase of infected/normal muscle was 6.82 ± 0.40,
17.11 ± 0.60, and 23.13 ± 1.00% at 30, 60 and 90 min of administration. Stable and higher %RCP, higher uptake in the infected
thigh, and spectral studies, recommend the 99mTc-STF for routine infection imaging.
Authors:S. Mirshojaei, M. Gandomkar, R. Najafi, S. Sadat Ebrahimi, M. Babaei, A. Shafiei, and M. Talebi
Cefotaxime, a cephalosporin antibiotic, used to treat bacterial infections was investigated to label with 99mTc. Labeling was performed using sodium dithionite as a reducing agent at 100 °C for 10 min and radiochemical analysis involved
ITLC and HPLC methods. The stability of labeled antibiotic was checked in the presence of human serum at 37 °C up to 24 h.
The maximum radiolabeling yield was 92 ± 2%. Bacterial binding assay was performed with S. aureus and the in vivo distribution was studied in mice. Images showed minimal accumulation in non-target tissues, with an average
target/non-target ratio of 2.89 ± 0.58.
Garenoxacin (GXN) was modified to its dithiocarbamate followed by radiolabeling with technetium-99m (99mTc) through [99mTc-N]2+ core. The suitability of the 99mTcN–Garenoxacin dithiocarbamate (GXND) complex as a potential multiresistant Staphylococcus aureus (MDRSA) and penicillin-resistant Streptococci (PRSC) infection radiotracer was assessed in artificially infected rats (AFRT). The radiolabeled complex was investigated
for its radiochemical purity (RCP), permanence in serum using HPLC and TLC methods. In vitro binding with MDRSA and PRSC was
performed at 37 °C. The 99mTcN–GXND showed maximum RCP of 98.00 ± 0.22% and remained more than 90% stable up to 4 h. The 99mTcN–GXND showed saturated in vitro binding with living MDRSA and PRSC, respectively. The complex showed normal biodistribution
in healthy rats (HRT), however in AFRT, seven fold uptakes was observed in infected muscle as compared to inflamed and normal
muscles. Based on the high RCP, stability in serum, better in vitro binding with bacteria, biodistribution behavior and the
target to non-target (infected to inflamed muscle) ratio, we recommend the 99mTcN–GXND complex for in vivo investigation of MDRSA and PRSC infection in human.
Gatifloxacin (GTN) was derivatized to its dithiocarbamate derivative and its radiolabeling with technetium-99m (99mTc) using the [99mTc≡N]2+ core was investigated. The appropriateness of the 99mTcN–gatifloxacin dithiocarbamate (99mTcN–GTND) complex as a potential multi-drug-resistance Streptococcus pneumoniae (MRSP) infection radiotracer was evaluated in terms of stability in saline, serum, in vitro binding with MRSP and biodistribution
in artificially MRSP infected Male Wistar Rats (MWR). In saline the 99mTcN–GTND complex showed more than 90% labeling yield up to 4 h with a maximum yield of 98.25 ± 0.20%, after reconstitution.
In serum the 99mTcN–GTND complex showed stability up to 16 h of incubation with the appearance of insignificant 15.95% undesirable side products.
The 99mTcN–GTND complex demonstrated saturated in vitro binding with MRSP with a maximum value of 75.50 ± 1.00% (at 90 min). In MWR
model of group A, almost six times higher uptake of the labeled GTND was monitored in the muscle of MWR infected with live
MRSP as compared to the inflamed and normal muscles. Based on the higher labeling yield in saline, in vitro stability in serum,
saturated in vitro binding with live MRSP and promising biodistribution in MWR model we recommend 99mTcN–gatifloxacin dithiocarbamate complex as a potential MRSP infection radiotracer.
Nitrofurantoin (NFN) radiolabeling with technetium-99m (99mTc) was investigated using different concentration of the NFN, sodium pertechnetate (Na99mTcO4), reducing agent (SnCl2) at different pH ranges (5.1–6.00). The suitability of the 99mTc-NFN was evaluated in terms of the radiochemical purity (RCP) yield, in vitro stability in saline, serum, in vitro binding
with E. coli, biodistribution in E. coli infected model rat (ERT), and scintigraphic accuracy in E. coli infected model rabbit (EBT). The superlative radiochemical succumb at 2.5 mg NFN, 125 μL of SnCl2 (1 μg/μL in 0.01 N HCl), 2.5 mCi of Na99mTcO4, at pH 5.2 at 30, 60, 90, and 120 min after reconstitution was 64.50 ± 0.11, 97.50 ± 0.16, 94.25 ± 0.10, 92.15 ± 0.14 and
90.75 ± 0.0.13%. The complex was found stable in saline and serum for 90% up to 120 min and showed 50–65% in vitro binding
with E. coli. The absorption of the 99mTc-NFN, primarily at E. Coli infected (ECT) muscle of ERT was lower but after 60 min it went up to 7.25 ± 0.17%. The absorption in the blood, liver, spleen,
stomach, intestines, inflamed muscle (N.T1) and normal muscle (N.T2) went down while in the kidney and urine it went up with
time. The ratio of the ECT/N.T1 was 7:1 and N.T2/N.T1 was 2:1. The Whole Body Static (WBS) imaging of the ERB confirmed the
suitability of the 99mTc-NFN as radiotracer. The superlative radiochemical succumb, significant in vitro stability in saline and serum, in vitro
binding with E. coli, ideal biodistribution and scintigraphic accuracy confirmed the viability of the 99mTc-NFN as radiotracer for infection.
The radiolabeling of trovafloxacin dithiocarbamate (TVND) with technetium-99m using [99mTc-N]2+ core was investigated and biologically assessed as prospective infection imaging agent. The achievability of the 99mTcN-TVND complex as a future MRSA infection radiotracer was investigated in artificially methicillin-resistant Staphylococcus aureus (MRSA) infected male Sprague–Dawley rats (MSDR). Radiochemically the 99mTcN-TVND complex was characterized in terms of radiochemical purity (RCP) in saline, in vitro permanence in serum, in vitro
binding with MRSA and biodistribution in living and heat killed MRSA infected MSDR. Radiochemically the complex showed stability
in saline with a 97.90 ± 0.22% yield and serum at 37 °C up to 4 h. The 99mTcN-TVND complex showed saturated in vitro binding with MRSA. Normal in vivo uptake in the MRSA infected MDRS was observed
with a five fold uptake in the infected muscle as compared to inflamed and normal muscles. The high RCP values, in vitro permanence
in serum, better in vitro binding with MRSA, biodistribution behavior and the target to non-target (infected to inflamed muscle)
ratios posed the 99mTcN-TVND complex as a promising MRSA infection radiotracer.