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Synthetic antimicrobial peptide fragment, 99mTc-Ubiquicidin 29–41, is shown to be sensitive and also specific for imaging bacterial infections. We undertook this study to explore the advantage of using a positron emission agent, 68Ga-DOTA-Ubiquicidin 29–41 (68Ga-DOTA-UBI), for detecting Staph-A infection in an animal model, and also evaluated its ability to distinguish a turpentine-induced sterile inflammation in an animal model. Pure Ga-68 was freshly eluted from a 68Ge/68Ga generator (IGG-100). DOTA-UBI (50 μg) was ra diolabeled with pure Ga-68 (500MBq) by incubating the reaction mixture at pH 4.5 for 10 min, 95°C. Rats were infected with Staph-A at the hind leg joint of rats to form bacterial abscess. Sterile inflammation was induced in the right thigh muscle by injecting 200 μl of 100% turpentine oil. Rats were injected intravenously with 10–15 MBq of tracer, and images were acquired at different time intervals with Siemens (Biograph mCT) positron emission tomography computed tomography scanner. The early images at 6 min postinjection clearly indicated mild uptake of the agent corresponding to the infection site, which increased dramatically at 20, 30, and 60 min postinjection. The target to background ratio (T/B) increased significantly over the same time period of study (1.6, 4.2, and 6.1, respectively). There was a mild uptake of 68Ga-DOTA-UBI at the site corresponding to sterile inflammation at 6 min postinjection, which was rapidly washed off as seen at 25 and 45 min images. The images indicated fast clearance of the agent from liver and soft tissues within 6 min. Control rats showed similar biodistribution of activity. The mild uptake of 68Ga-DOTA-UBI at the corresponding Staph-A infection lesion and very fast kinetics of clearance from the blood pool and soft tissues suggested a very high clinical potential for this agent. The absence of uptake of the agent at sterile inflammation site suggests that the agent may be useful in distinguishing infection from inflammation.

A translocator protein 18 kDa targeted radiotracer, N,N-diethyl-2-(2-(4-[18F]fluorophenyl)-5,7-dimethylpyrazolo[1,5-a] pyrimidin-3-yl) acetamide ([18F]FDPA), was automated synthetized and evaluated for cardiac inflammation imaging. Various reaction conditions for an automated synthesis were systematically optimized. MicroPET/CT imaging were performed on normal rats and rats with myocardial infarction (MI). Normalized SUV ratios of [18F]FDPA to [13N]NH3 (NSRs) in different regions were calculated to normalize the uptake of [18F]FDPA to perfusion. The amount of TBAOMs and the volume/proportion of water were crucial for synthesis. After optimization, the total synthesis time was 68 min. The non-decay corrected radiochemical yields (RCYs) and molar activities were 19.9 ± 1.7% and 169.7 ± 46.5 GBq/μmol, respectively. In normal rats, [18F]FDPA showed a high and stable cardiac uptake and fast clearance from other organs. In MI rats, NSRs in the peri-infarct and infarct regions, which were infiltrated with massive inflammatory cells revealed by pathology, were higher than that in the remote region (1.20 ± 0.01 and 1.08 ± 0.10 vs. 0.89 ± 0.05, respectively). [18F]FDPA was automated synthesized with high RCYs and molar activities. It showed a high uptake in inflammation regions and offered a wide time window for cardiac imaging, indicating it could be a potential cardiac inflammation imaging agent.

Small-molecular and macromolecular optical probes based on an iridium complex chromophore were designed for detecting hypoxic inflammation in this work. The optical probes had a large conjugated ligand that could extend its phosphorescence emission to the red-wavelength region, thus increasing the tissue penetration depth of the optical signal. Due to good water solubility, the macromolecular optical probe could image both monolayer cells and three-dimensional multicellular spheroids. Moreover, this macromolecular probe was able to effectively image inflammation and distinguish healthy and inflammatory regions in a mouse model of lipopolysaccharide (LPS)-induced inflammation with low background interference. Furthermore, we integrated the hydrophobic small-molecular probe into the polyurethane thin film, and the resulting film successfully monitored the inflammation of chronic wounds in a mouse model. This work demonstrated the great potential of the iridium complex in optical imaging hypoxia and hypoxia-associated inflammation and will have significant impact on the design of high-sensitivity sensors for the detection of hypoxia.

To improve the bioimaging signal-to-noise ratio (SNR), long-term imaging capability, and decrease the potential biotoxicity, an in vivo cross-linking strategy was developed by using sub-10 nm, glutathione-modified, lanthanide nanoprobes. After administration, the nanoprobes cross-link in response to reactive oxygen species (ROS) at the inflamed area and enable the quick imaging of ROS in the second near-infrared (NIR-II) window. These nanoprobes could be rapidly excreted due to their ultra-small size. This strategy may also be applied to other ultra-small contrast agents for the precise bioimaging by in situ lesion cross-linking.

Positron Emission Tomography is an attractive imaging modality for monitoring the migration of cells to pathological tissue. We evaluated a new method for radiolabelling leukocytes with zirconium-89 (89Zr) using chitosan nanoparticles (CN, Z-average size 343 ± 210 nm and zeta potential +46 ± 4 mV) as the carrier. We propose that cell uptake of 89Zr-loaded CN occurred in a two-step process; cell membrane interaction with 89Zr-loaded CN was followed by a slower cell internalisation step.

Contains fulltext : 229164.pdf (Publisher’s version ) (Open Access) Perfluorocarbons hold great promise both as imaging agents, particularly for (19)F MRI, and in therapy, such as oxygen delivery. (19)F MRI is unique in its ability to unambiguously track and quantify a tracer while maintaining anatomic context, and without the use of ionizing radiation. This is particularly well-suited for inflammation imaging and quantitative cell tracking. However, perfluorocarbons, which are best suited for imaging - like perfluoro-15-crown-5 ether (PFCE) - tend to have extremely long biological retention. Here, we showed that the use of a multi-core PLGA nanoparticle entrapping PFCE allows for a 15-fold reduction of half-life in vivo compared to what is reported in literature. This unexpected rapid decrease in (19)F signal was observed in liver, spleen and within the infarcted region after myocardial infarction and was confirmed by whole body NMR spectroscopy. We demonstrate that the fast clearance is due to disassembly of the ~200 nm nanoparticle into ~30 nm domains that remain soluble and are cleared quickly. We show here that the nanoparticle ultrastructure has a direct impact on in vivo clearance of its cargo i.e. allowing fast release of PFCE, and therefore also bringing the possibility of multifunctional nanoparticle-based imaging to translational imaging, therapy and diagnostics.

Although biological fluorescence imaging in the second near-infrared window (NIR-Ⅱ, 1000-1700 nm) has embodied the advantages of deep tissue penetration, low background noise and high spatial resolution, shortage of high quantum yield (QY) organic fluorophores has become the bottleneck for further development to this field. Now, an ingenious strategy is proposed to address this: constitutional isomerization by utilizing the molecular design philosophy of aggregation-induced emission (AIE). By solely shifting alkyl chain from meta to ortho position, the resulting twisted structure drives the NIR-Ⅱ fluorophores from aggregation-caused quenching (ACQ) to AIE. In this way, the AIE luminogen (AIEgen), 2TT-oC6B, is provided with an emission peak at 1030 nm and a QY of 11% in nanoparticles, one of the highest reported so far. To endow the targeting ability to deeply located diseases, neutrophils (NEs), the most common immune cells, are used to penetrate the brain tissues. Herein, we show that NEs carrying 2TT-oC6B NPs can penetrate the brain and visualize the deeply located inflammation through intact scalp and skull (3 mm of depth). Notably, the bright 2TT-oC6B fluorophore contributes to a significantly enhanced signal-to-noise ratio of 30.6 in brain inflammation site, which is among the best ones to date. This modern molecule design philosophy could enable a powerful platform for high QY fluorophores and their potential biological applications.

Gallium-68 citrate has been successfully applied in the PET imaging of infections and inflammation in some centers; however further evaluation of the tracer in inflammation models is of great importance.68Ga-citrate prepared from [68Ga]GaCl3 (eluted form an SnO2 based 68Ge/68Ga generator) and sodium citrate at optimized conditions followed by quality control tests was injected to normal and turpentine-oil induced rats PET/CT imaging studies up to 290 min.68Ga-citrate was prepared with acceptable radiochemical purity (99 ITLC,99% HPLC), specific activity (28-30 GBq/mM), chemical purity (Sn, Fe0.3 ppm; Zn0.2 ppm) in 15 min at 50°C. PET/CT imaging of the tracer demonstrated early detection of inflamed site in animal models in 60-80 min.This study demonstrated possible early detection of inflammation foci in vivo using 68Ga-citrate prepared using commercially available 68Ge/68Ga generators for PET imaging.

Mixed leukocyte (white blood cells [WBCs]) trafficking using positron emission tomography (PET) is receiving growing interest to diagnose and monitor inflammatory conditions. PET, a high sensitivity molecular imaging technique, allows precise quantification of the signal produced from radiolabelled moieties. We have evaluated a new method for radiolabelling WBCs with either zirconium-89 ((89) Zr) or copper-64 ((64) Cu) for PET imaging. Chitosan nanoparticles (CNs) were produced by a process of ionotropic gelation and used to deliver radiometals into WBCs. Experiments were carried out using mixed WBCs freshly isolated from whole human blood. WBCs radiolabelling efficiency was higher with [(89) Zr]-loaded CN (76.8 ± 9.6% (n = 12)) than with [(64) Cu]-loaded CN (26.3 ± 7.0 % (n = 7)). [(89) Zr]-WBCs showed an initial loss of 28.4 ± 5.8% (n = 2) of the radioactivity after 2 h. This loss was then followed by a plateau as (89) Zr remains stable in the cells. [(64) Cu]-WBCs showed a loss of 85 ± 6% (n = 3) of the radioactivity after 1 h, which increased to 96 ± 6% (n = 3) loss after 3 h. WBC labelling with [(89) Zr]-loaded CN showed a fast kinetic of leukocyte association, high labelling efficiency and a relatively good retention of the radioactivity. This method using (89) Zr has a potential application for PET imaging of inflammation.

Easy and early detection of infection and inflammation is essential for early and effective treatment. In this study, PEGylated micelles were designed and both micelles and Levofloxacin were radiolabeled with 99mTcO4- to develop potential radiotracers for detection of infection/inflammation. Radiolabeling efficiency, in vitro stability and bacterial binding of 99mTc-Levofloxacin and 99mTc-micelles were compared. The aim of this study is to formulate and compare 99mTc-Levofloxacin and 99mTc-micelles as infection and inflammation agents having different mechanisms for the accumulation at infection and inflammation site. PEGylated micelles were designed with a particle size of 80 ± 0.7 nm and proper characterization properties. High radiolabeling efficiency was achieved for 99mTc-Levofloxacin (96%) and 99mTc-micelles (87%). The radiolabeling efficiency was remained stable with some insignificant alterations for both radiotracers at 25 °C for 24 h. Although in vitro bacterial binding of 99mTc-levofloxacine was higher than 99mTc-micelles, 99mTc-micelles may also be evaluated potential agent due to long circulation and passive accumulation mechanisms at infection/inflammation site. Both radiopharmaceutical agents exhibit potential results in design, characterization, radiolabeling efficiency and in vitro bacterial binding point of view., Graphical abstract Image 1, Highlights • PEGylated, nanosized micelles were designed and characterized. • High radiolabeling efficiency was achieved for both Levofloxacin and micelles. • Labeling efficiency was remained stable for both radiotracers at 25 °C for 24 h. • 99mTc-Levofloxacin showed high and specific bacterial binding in vitro. • 99mTc-micelles showed lesser in vitro bacterial binding.

Experiments on labeling of diclofenac, an anti-inflammatory drug, with 99m Tc were performed. High (about 96%) yield of 99m Tc-diclofenac is reached under the following conditions: 50 μg of Sn(II), 100 μg of the substrate, 30 min, pH 7. 99m Tc-diclofenac was stable for 4 h. Biological distribution of 99m Tc-diclofenac was investigated in mice bearing inflammations experimentally induced in the left thigh by Escherichia coli (bacterial infection model) and turpentine oil (sterile inflammation model). The uptake ratio in the inflamed and contralateral thighs (target-to-nontarget, T/NT) was evaluated. In the case of bacterial infection, the T/NT ratio only slightly exceeds unity, whereas in the case of sterile inflammation it reaches 4.46 ± 0.07 in 2 h. Thus, 99m Tc-diclofenac allows differentiation between septic and aseptic inflammation and can be recommended for further clinical trials.

Estrogens may have pro- and anti-inflammatory properties depending on the situation and the involved tissue. 2-Aminoestrone-3-methyl ether as an estrogenic derivative was prepared with a yield of 55 % and well characterized. 99mTc–2-aminoestrone-3-methyl ether radiotracer was synthesized to study its inflammatory binding specificity as a novel selective radiopharmaceutical for inflammation imaging. In-vivo biodistribution study of 99mTc–2-amino estrone-3-methyl ether complex in both bacterial infection and sterile inflammation showed high and rapid accumulation of 99mTc–2-aminoestrone-3-methyl ether complex at the site of sterile inflammation compared to bacterial infection sites (target-to-non target ratio equal to 4.12 ± 0.02). This high biological accumulation in inflamed cells suggests that 99mTc–2-aminoestrone-3-methyl ether complex may be suitable as a potential selective radiotracer able to image inflammatory sites.

Inflammatory processes can reliably be assessed by 19 F MRI using perfluorocarbons (PFCs), which is primarily based on the efficient uptake of emulsified PFCs by circulating cells of the monocyte–macrophage system and subsequent infiltration of the 19 F-labeled cells into affected tissue. An ideal candidate for the sensitive detection of fluorineloaded cells is the biochemically inert perfluoro-15-crown-5 ether (PFCE), as it contains 20 magnetically equivalent 19 F atoms. However, the biological half-life of PFCE in the liver and spleen is extremely long, and so this substance is not suitable for future clinical applications. In the present study, we investigated alternative, nontoxic PFCs with predicted short biological half-lives and high fluorine content: perfluorooctyl bromide (PFOB), perfluorodecalin (PFD) and trans-bis-perfluorobutyl ethylene (F-44E). Despite the complex spectra of these compounds, we obtained artifact-free images using sine-squared acquisition-weighted three-dimensional chemical shift imaging and dedicated reconstruction accomplished with in-house-developed software. The signal-to-noise ratio of the images was maximized using a Nutall window with only moderate localization error. Using this approach, the retention times of the different PFCs in murine liver and spleen were determined at 9.4T. The biological half-lives were estimated to be 9days (PFD), 12days (PFOB) and 28days (F-44E), compared with more than 250days for PFCE. In vivo sensitivity for inflammation imaging was assessed using an ear clip injury model. The alternative PFCs PFOB and F-44E provided 37% and 43%, respectively, of the PFCE intensities, whereas PFD did not show any signal in the ear model. Thus, for in vivo monitoring of inflammatory processes, PFOB emerges as the most promising candidate for possible future translation of 19 FM R inflammation imaging to human applications. Copyright © 2013 John Wiley & Sons, Ltd. Additional supporting information may be found in the online version of this article at the publisher’s web site.

Labeling of Meloxicam with 99mTc was done by direct addition of pertechnetate in isotonic solution to Sn-Meloxicam solution. High labeling yield (98%) was attained in 30 min at room temperature. The effect of various factors on the labeling yield was studied. No less than 0.5 mg of Meloxicam should be used to prevent the formation of colloids in the reaction medium. 75 μg of stannous chloride dihydrate was found to be sufficient to reduce all pertechnetate without the detection of free pertechnetate or colloids in the reaction mixture. The labeling should be done in alkaline solutions (pH 9–11). The labeled compound was separated and purified by HPLC. The biological distribution in infected mice demonstrates the suitability of 99mTc-labeled Meloxicam for inflammation and tumor imaging.

BACKGROUND: There is currently no clinical imaging technique available to assess the degree of inflammation associated with atherosclerotic plaques. This study aims to develop targeted superparamagnetic particles of iron oxide (SPIO) as a magnetic resonance imaging (MRI) probe for detecting inflamed endothelial cells. METHODS: The in vitro study consists of the characterisation and detection of inflammatory markers on activated endothelial cells by immunocytochemistry and MRI using biotinylated anti-P-selectin and anti-VCAM-1 (vascular cell adhesion molecule 1) antibody and streptavidin conjugated SPIO. RESULTS: Established an in vitro cellular model of endothelial inflammation induced with TNF-α (tumor necrosis factor alpha). Inflammation of endothelial cells was confirmed with both immunocytochemistry and MRI. These results revealed both a temporal and dose dependent expression of the inflammatory markers, P-selectin and VCAM-1, on exposure to TNF-α. CONCLUSION: This study has demonstrated the development of an in vitro model to characterise and detect inflamed endothelial cells by immunocytochemistry and MRI. This will allow the future development of contrast agents and protocols for imaging vascular inflammation in atherosclerosis. This work may form the basis for a translational study to provide clinicians with a novel tool for the in vivo assessment of atherosclerosis.

Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a ligand of inflammation-inducible vascular adhesion protein-1 (VAP-1). We compared 68Ga-DOTA- and 18F-fluorodeoxyribose- (FDR-) labeled Siglec-9 motif peptides for PET imaging of inflammation. Methods. Firstly, we examined 68Ga-DOTA-Siglec-9 and 18F-FDR-Siglec-9 in rats with skin/muscle inflammation. We then studied 18F-FDR-Siglec-9 for the detection of inflamed atherosclerotic plaques in mice and compared it with previous 68Ga-DOTA-Siglec-9 results. Lastly, we estimated human radiation dosimetry from the rat data. Results. In rats, 68Ga-DOTA-Siglec-9 (SUV, 0.88±0.087) and 18F-FDR-Siglec-9 (SUV, 0.77±0.22) showed comparable (P=0.29) imaging of inflammation. In atherosclerotic mice, 18F-FDR-Siglec-9 detected inflamed plaques with a target-to-background ratio (1.6±0.078) similar to previously tested 68Ga-DOTA-Siglec-9 (P=0.35). Human effective dose estimates for 68Ga-DOTA-Siglec-9 and 18F-FDR-Siglec-9 were 0.024 and 0.022 mSv/MBq, respectively. Conclusion. Both tracers are suitable for PET imaging of inflammation. The easier production and lower cost of 68Ga-DOTA-Siglec-9 present advantages over 18F-FDR-Siglec-9, indicating it as a primary choice for clinical studies.

The potential value of multiplexed positron emission tomography (PET) tracers in mice with turpentine-induced inflammation was evaluated and compared with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) for glucose metabolism imaging. These PET tracers included [18F]fluoromethylcholine ([18F]FCH) for choline metabolism imaging, (S-[11C]methyl)-D-cysteine ([11C]DMCYS) for amino acid metabolism imaging, [11C]bis(zinc(II)-dipicolylamine) ([11C]DPA-Zn2+) for apoptosis imaging, 2-(4-N-[11C]-methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB) for β amyloid binding imaging, and [18F]fluoride (18F−) for bone metabolism imaging. In mice with turpentine-induced inflammation mice, the biodistribution of all the tracers mentioned above at 5, 15, 30, 45, and 60 min postinjection was determined. Also, the time-course curves of the tracer uptake ratios for inflammatory thigh muscle (IM) to normal uninflammatory thigh muscle (NM), IM to blood (BL), IM to brain (BR), and IM to liver (LI) were acquired, respectively. Moreover, PET imaging with the tracers within 60 min postinjection on a clinical PET/CT scanner was also conducted. [18F]FDG and 18F− showed relatively higher uptake ratios for IM to NM, IM to BL, IM to BR, and IM to LI than [18F]FCH, [11C]DPA-Zn2+, [11C]DMCYS and [11C]PIB, which were highly consistent with the results delineated in PET images. The results demonstrate that 18F− seems to be a potential PET tracer for inflammation imaging. [18F]FCH and [11C]DMCYS, with lower accumulation in inflammatory tissue than [18F]FDG, are not good PET tracers for inflammation imaging. As a promising inflammatory tracer, the chemical structure of [11C]DPA-Zn2+ needs to be further optimized.

The objective of this study is to design fluorescent nanoprobes for inflammation imaging. An antibody against CD11b expressed on the surfaces of mouse macrophages (anti-CD11b), was fluorescently labeled. Protein G, which has an ability to bind the Fc region of antibody, was conjugated onto the surface of silica nanoparticles (SiNP). Then, the fluorescent-labeled anti-CD11b was orientedly immobilized to the SiNP surface through the specific protein G-antibody interaction. After the intravenous injection of anti-CD11b orientedly immobilized SiNP to the mouse model of acute interstitial nephritis, unilateral ureteral obstruction (UUO) of one kidney, the fluorescent intensity at the UUO and non-treated, normal kidneys was assessed. The anti-CD11b orientedly immobilized SiNP were accumulated in the UUO kidney to a significantly great extent compared with the normal, non-inflamed kidney. The fluorescence intensity of inflamed kidney 6 and 12 h after injection of the anti-CD11b orientedly immobilized SiNP were significantly higher than that of anti-CD11b randomly immobilized SiNP or free anti-CD11b injection. Histological experiments revealed that the anti-CD11b orientedly immobilized SiNP were associated with macrophages infiltrated into the inflammation site. It is concluded that the anti-CD11b orientedly immobilized SiNP are promising nanoprobes to image the inflammation site at a high intensity.

Interleukin-2 (IL2) binds with high affinity to the IL2 receptors overexpressed on activated T lymphocytes in various pathologic conditions. Radiolabeling of IL2 with a positron-emitting isotope could provide a tool for noninvasive PET of activated T cells in immune-mediated diseases. We report the labeling of IL2 with N-succinimidyl 4-F-18-fluorolbenzoate (F-18-SFB) for the synthesis of N-(4-F-18-fluorobenzoyl)interleukin-2 (F-18-FB-IL2) and the in vitro and in vivo evaluation of this novel radiopharmaceutical for the detection of IL2 receptor-positive cells by PET. Methods: F-18-SFB was efficiently prepared using a 3-step radiochemical pathway. Purified F-18-SFB was incubated with IL2 in borate buffer (pH 8.5) and ethanol at 50 degrees C for 10 min. F-18-FB-IL2 was purified by reversed-phase high-performance liquid chromatography. As in vitro quality controls, a biologic binding assay, sodium dodecyl sulfate polyacrylamide gel electrophoresis, mass spectrometry, and 3-chloroacetic acid precipitation stability tests were performed. Biodistribution studies were performed in BALB/c mice to evaluate the distribution of the tracer in healthy animals. PET experiments were performed in severe combined immunodeficiency disease mice inoculated with phytohemoagglutinin-activated human peripheral blood mononuclear cells (hPBMc). Whole-body images were acquired 30 min after injection of 5-15 MBq of F-18-FB-IL2. Results: F-18-SFB was produced with a 34%-38% radiochemical yield. The radiochemical purity after solid-phase extraction purification ranged from 93% to 96%. Conjugation of F-18-SFB to IL2 yielded F-18-FB-IL2 as the major product. The radiochemical yield of F-18-FB-IL2 after high-performance liquid chromatography purification was 25%-35% based on F-18-SFB. F-18-FB-IL2 was stable in plasma at 37 degrees C and capable of stimulating T cells to an extent similar to native IL2. A biodistribution study showed highest tracer uptake in the kidneys and bladder due to rapid renal clearance of the tracer. Small-animal PET images showed binding of F-18-FB-IL2 to activated hPBMc proportional to the number of injected cells. Conclusion: We report the successful labeling of IL2 with F-18 for PET of activated T lymphocytes. F-18-FB-IL2 is stable, is biologically active, and allows in vivo detection of activated T lymphocytes.

Small synthetic receptor-binding peptides are the agents of choice for diagnostic imaging and radiotherapy of cancers due to their favorable pharmacokinetics. Molecular modification techniques permit the synthesis of a variety of bioactive peptides with chelating groups, without compromising biological properties. Various techniques have been developed that allow efficient and site-specific labeling of peptides with clinically useful radionuclides such as (99m)Tc, (123)I, (111)In, and (18)F. Among them, (99m)Tc is the radionuclide of choice because of its excellent chemical and imaging characteristics. Recently, many (99m)Tc-labeled peptides have proven to be useful imaging agents. Beside (99m)Tc-labeled peptides, several peptides radiolabeled with (111)In and (123)I have been prepared and characterized. In addition, (18)F-labeled peptides hold clinical potential due to their ability to quantitatively detect and characterize a variety of human diseases using positron-emission tomography. The availability of this wide range of peptides labeled with different radionuclides offers multiple diagnostic and therapeutic applications. Various receptors are over-expressed in particular tumor types and peptides binding to these receptors can be used to visualize tumor lesions scintigraphically. Thus, radiolabeled peptides have potential use as carriers for the delivery of radionuclides to tumors, infarcts, and infected tissues for diagnostic imaging and radiotherapy. Many radiolabeled peptides are currently under investigation to determine their potential as imaging agents. These peptides are designed mainly for thrombus, tumor, and infection/inflammation imaging. This article presents recent developments in small synthetic peptides for imaging of thrombosis, tumors, and infection/inflammation.

Introduction: Interleukin-2 (IL-2) when radiolabelled with Tc-99m has been proved useful in imaging the side of lymphocytic infiltration in patients with autoimmune disorders and plays a significant role as a T-cell imaging agent. However, the labelling procedures used so far appeared to be rather complex and laborious. The aim of present study was to develop an efficient procedure of Tc-99m-labelling of recombinant human interleukin-2 (rhIL-2) via hydrazinonicotinamide (HYNIC) to develop a dry kit formulation.Methods: Various molar ratios of rhIL-2/HYNIC (from 1:2 to 1:12) were used at the conjugation step. The conjugates were purified on a PD-10 column to remove the excess of unbound HYNIC, as well as of any aggregates. The final peptide concentration was quantified by the BCA method, and the number of HYNIC molecules incorporated into a rhIL-2 molecule was determined based on the reaction with 2-sulfobenzaldehyde. The Tc-99m-labelling was optimized using various amounts of HYNIC rhIL-2, Tc-99m, SnCl2, tricine and nicotinic acid (NA). Quality control included GF-HPLC, ITLC, SDS-PAGE and biological assay. Biodistribution studies were performed in Swiss mice and Wistar rats.Results: Generally, the highest radiolabelling yields were achieved when the HYNIC rhIL-2 conjugates of ca. 2-4 HYNIC molecule substitution ratios were used. The optimal pH of the reaction medium was found to be in the range of 6.5 to 7.0. GF-HPLC analysis indicated that monomer and aggregates of Tc-99m-HYNIC rhIL-2 are formed during radiolabelling. At optimized conditions of wet radiolabel ling, the Tc-99m-HYNIC rhIL-2 monomer was obtained with radiochemical purity >99%, specific activity of ca. 4 GBq/mg rhIL-2 and overall yield lea. 65%. The two-vial freeze-dried kit was prepared: the first vial contained 30 mu g HYNIC rhIL-2, coligands, buffer and antioxidant; the second vial contained tricine and SnCl2. The monomer of Tc-99m-HYNIC rhIL-2 was obtained by gel chromatography on a PD-ID column. No differences between labelled and unlabelled IL2 in terms of biological activity were observed.Conclusions: Our study shows that rhIL-2 can be efficiently radiolabelled with Tc-99m via HYNIC, with tricine and NA as co-ligands using a two-vial freeze-dried kit. This enables the preparation of sterile and ready-to-use Tc-99m-HYNIC(tricine,NA)-rhIL-2 within 1 h. (C) 2010 Elsevier Inc. All rights reserved.

A neutrophil-specific peptide, cinnamoyl-F(D)LF(D)LFK (cFLFLFK), was conjugated consecutively with a polyethylene glycol moiety (3.4K) and 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetic acid (DOTA) to form cFLFLFK-PEG-DOTA. After (64)Cu labeling, Positron Emission Tomography (PET) imaging was successfully able to detect mouse lung inflammation.

Barium concretions are a rare complication of barium administration resulting from prolonged retention of the barium within the bowel. Indium-111 white blood cell localization studies are a sensitive and specific indicator of inflammation. Indium-111 white blood cell localization was noted

The ability to selectively target molecules to specific sites within the body has been one of the most coveted goals in experimental and clinical therapeutics. The performance of many diagnostic and therapeutic agents, both existing and promising new ones (like biomacromolecules such as proteins and DNA), would benefit greatly from targeted delivery strategies. Perhaps the major reason for the resurgence of interest in liposomal delivery systems for targeted delivery relates to the development of long-circulating “stealth” liposomes. As discussed elsewhere in this volume, the principal results have been obtained by modification of the liposomal surface through the use of the hydrophilic polymer polyethylene glycol conjugated to the lipid phosphatidylethanolamine (PEG-PE). This contribution will discuss the utility of PEG-coated liposomes (often referred to as sterically stabilized liposomes) for the imaging and therapy of infectious and inflammatory diseases.

A new agent originally introduced for localizing inflammatory lesions is Tc-99m human immunoglobulin G (HIG). Recently, focal uptake of this agent was seen in malignant lesions in a limited number of patients during inflammation imaging studies. In this prospective clinical study, the authors aimed to evaluate the uptake of Tc-99m HIG in malignant lesions. Nineteen patients with histopathologically proven malignant tumors were studied (seven had distant metastases, the primary tumor was surgically removed in two). There was no evidence of inflammation or infection in any patient. The authors imaged patients at 1, 4, and 24 hours after injection. The dose was 15-20 mCi (555-740 MBq). Focal uptake was detected in the primary tumor in six patients and in the metastases in five patients, raising some question about the specificity of Tc-99m HIG imaging for the detection of inflammation and infection.

Tc-99m dextran has been shown to have inflammation imaging capability. Two cases are presented: one with Meckel's diverticulum and another with osteomyelitis. In both, the agent correctly identified the abnormal sites. It appeared to be better than Tc-99m pertechnetate and Tc-99m MDP in these conditions. Its nonprotein nature, easy and stable tagging, and good target-to-nontarget ratio make it a practical inflammation imaging radiotracer.

Item does not contain fulltext Scintigraphic imaging of infection and inflammation is a powerful diagnostic tool in the management of patients with infectious or inflammatory diseases. Most infectious and inflammatory foci can be visualized accurately with radiolabeled autologous leukocytes. However, preparation of this radiopharmaceutical is laborious and requires the handling of potentially contaminated blood. Nowadays, a few radiopharmaceuticals are available that could replace radiolabeled leukocytes, such as: 67Ga-citrate, 99mTc-IgG and 99mTc-labeled antigranulocyte antibody preparations. Furthermore, various agents labeled with 99mTc are currently developed for this application: chemotactic peptides, cytokines and liposomes. Here, the characteristics and the diagnostic potential of established and experimental radiopharmaceuticals for infection and inflammation imaging are reviewed.

Background Vascular adhesion protein-1 (VAP-1) is an adhesion molecule that plays a key role in recruiting leucocytes into sites of inflammation. We have previously shown that 68Gallium-labelled VAP-1-targeting peptide (68Ga-DOTAVAP-P1) is a positron emission tomography (PET) imaging agent, capable of visualising inflammation in rats, but disadvantaged by its short metabolic half-life and rapid clearance. We hypothesised that prolonging the metabolic half-life of 68Ga-DOTAVAP-P1 could further improve its imaging characteristics. In this study, we evaluated a new analogue of 68Ga-DOTAVAP-P1 modified with a mini-polyethylene glycol (PEG) spacer (68Ga-DOTAVAP-PEG-P1) for in vivo imaging of inflammation. Methods Whole-body distribution kinetics and visualisation of inflammation in a rat model by the peptides 68Ga-DOTAVAP-P1 and 68Ga-DOTAVAP-PEG-P1 were evaluated in vivo by dynamic PET imaging and ex vivo by measuring the radioactivity of excised tissues. In addition, plasma samples were analysed by radio-HPLC for the in vivo stability of the peptides. Results The peptide with the mini-PEG spacer showed slower renal excretion but similar liver uptake as the original peptide. At 60 min after injection, the standardised uptake value of the inflammation site was 0.33 ± 0.07 for 68Ga-DOTAVAP-P1 and 0.53 ± 0.01 for 68Ga-DOTAVAP-PEG-P1 by PET. In addition, inflammation-to-muscle ratios were 6.7 ± 1.3 and 7.3 ± 2.1 for 68Ga-DOTAVAP-P1 and 68Ga-DOTAVAP-PEG-P1, respectively. The proportion of unchanged peptide in circulation at 60 min after injection was significantly higher for 68Ga-DOTAVAP-PEG-P1 (76%) than for 68Ga-DOTAVAP-P1 (19%). Conclusion The eight-carbon mini-PEG spacer prolonged the metabolic half-life of the 68Ga-DOTAVAP-P1 peptide, leading to higher target-to-background ratios and improved in vivo PET imaging of inflammation.