99mTc-Alafosfalin: an antibiotic peptide infection imaging agent

Tsopelas, Chris; Penglis, S.; Ruszkiewicz, Andrew; Bartholomeusz, F. D.L.

doi:10.1016/s0969-8051(02)00348-7

Cited by 36 publications

(22 citation statements)

References 22 publications

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“…Others that have been considered as infection specific agents include the small peptide analog of lactoferrin (4); labeled alafosfalin (5) and human neutrophil peptide-1 (2,6). This laboratory is investigating the use of 99m Tc-labeled bacteriophage for infection specific imaging (7).…”

Section: Introductionmentioning

confidence: 99%

Investigation of four 99mTc-labeled bacteriophages for infection-specific imaging

Rusckowski

Gupta

Liu

et al. 2008

Nuclear Medicine and Biology

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This laboratory is investigating radiolabeled bacteriophages for specific detection of infection through gamma imaging. Previously a 99m Tc-labeled M13 phage demonstrated specific binding for its host Escherichia coli in vitro and in mice through imaging.Methods-This study was extended to phages P22, E79, VD-13, and phage 60. Each was radiolabeled with 99m Tc using the chelator MAG 3 , labeled phages were evaluated for binding to host and non host bacteria in vitro and in a mouse model. Results-In vitro each 99mTc-phage bound to its host at least 4-fold higher than to non host bacteria. For example, 99m Tc-E79 showed 10-to 20-fold greater binding to host Pseudomonas aeruginosa than non host Escherichia coli and Salmonella enterica, respectively. 99m Tc-phage 60 showed 20-fold greater binding to host Klebsiella pneumoniae over non hosts. Mice received host or non host bacteria in one thigh and 3 h later the 99m Tc-phages were administered iv. After a further 3 h the tissues were counted. Liver accumulation was highest for 99m Tc-E79, averaging 39% compared to an average of 13% for the other 99m Tc-phages. Animals infected with host bacteria showed infected thigh to normal thigh ratios of 14.2 for 99m Tc-E79, 2.9 for 99m Tc-P22, 3.5 for 99m Tc-VD-13 and 2.1 for 99m Tc-phage 60.Conclusions-Although specific host binding was observed in vitro for each of the these four 99m Tc-phages, only 99m Tc-E79 showed specificity for its host in an in vivo model.

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Section: Introductionmentioning

confidence: 99%

Investigation of four 99mTc-labeled bacteriophages for infection-specific imaging

Rusckowski

Gupta

Liu

et al. 2008

Nuclear Medicine and Biology

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“…The 99m Tc-immunoglobulins examined in this study have resulted in higher T/C ratios than other reported agents including 99m 99m Tc-ciprofloxacin 29 and radioactive liposomes 30 in rat models of infection. However the ratios are lower than 99m Tc-tin colloidlabelled-leukocytes, 17 indicating that these cells actively participate over a longer duration than immunoglobulins in the inflammatory process. This is one of the main reasons why radioactive leukocytes still feature prominently in the routine diagnostic imaging of infection and inflammation.…”

Section: Discussionmentioning

confidence: 87%

“…The mechanism of concentration of immunoglobulins in the S. aureas infection is still uncertain 31 but has been proposed to involve Fc receptor binding with local inflammatory cells, or other 'non-specific' retention processes such as increased permeability. Increased permeability is unlikely to explain the tracer retention mechanism because the non-specific small molecule 99m Tc-DTPA in the same rat model was reported to give lower T/C ratios than these immunoglobulins as 3.5-1.9 over 1-4 h, 17 or the larger soluble polymer 99m Tc-dextran gave T/C of $2-3.5 (versus 99m Tc-DTPA with $1-3.5) over 1-6 h in a mouse model of sterile inflammation. 32 The Fc portion of antibodies is known to bind with Fcg receptors on the surfaces of monocytes, macrophages and neutrophils to initiate immunomodulatory functions such as phagocytosis, release of inflammatory mediators, antigen expression and generation of oxygen radicals.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of99mTc-immunoglobulins for imaging infection in the rat

Tsopelas

Penglis

Miller

et al. 2006

J Label Compd Radiopharm

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SummaryThree immunoglobulin molecules were evaluated as infection imaging agents in a rat model of S. aureas infection:99m 99m Tc-human immunoglobulin (HIG) and 99m Tc-rat immunoglobulin (RIG). Infliximab is a chimeric monoclonal antibody specific for human tumour necrosis factor alpha (TNFa). Tc-HIG was chosen as an exogenous protein and 99m Tc-RIG as an endogenous marker. Each immunoglobulin was treated with 2-mercaptoethanol and the reduced antibody was isolated by size exclusion chromatography. In combination with Sn II -methylenediphosphonic acid, cold kit formulations were prepared. Native and reduced infliximab were tested for rat TNFa binding ability in vitro. A focal intramuscular infection of S. aureus (1 Â 10 8 colony forming units) was induced in the left thigh muscle of rats, that developed for 24 h. In separate experiments each tracer was administered by intravenous injection, then whole body scintigraphic imaging and biodistribution studies were performed at 1 and 4 h later. 99m 99m Tc-HIG and 99m Tc-RIG were prepared with 595% radiochemical purity from stable cold kits.Results from the organ assay gave infected (target) to non-infected (control) muscle ratios for 99m Tc-infliximab as 5.7 AE 0.8, 7.1 AE 1.2, 99m Tc-HIG gave 3.1 AE 1.1, 7.8 AE 1.2, and 99m Tc-RIG 7.9 AE 0.3, 12.5 AE 1.5 at 1 and 4 h, respectively. Infliximab and Sn II -infliximab did not bind to rat TNFa by the in vitro assay. Although lacking specific affinity for TNFa, 99m Tc-infliximab accumulated at infectious sites in vivo. 99m Tc-infliximab gave similar infection uptake ratios to 99m Tc-HIG at 1 and 4 h, but these proteins were inferior in comparison to 99m Tc-RIG, and is likely to be due to

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“…The organ uptake values are consistent with a previous study in Staphylococcus aureas infected rats where liver (83%) and spleen (12%) activity totalled >90% of the injected dose of 99m Tc-SnF 2 labelled leucocytes at 1 h post injection. 10 Pre-injection of SnF 2 colloid resulted in a significant increase in liver activity and a 30% decrease in spleen activity. Tc-neutrophils in whole blood gave an identical Tc-SnF 2 colloid (with no cold colloid pre-injection) for the lungs (p=0.260), liver (p=0.162) and spleen (p=0.202).…”

Section: Distribution Of 99m Tc-snf 2 Labelled Neutrophils In Whole Bmentioning

confidence: 96%

Preparation and biological evaluation of ^99mTc‐stannous fluoride colloid‐labelled‐leucocytes in rats ^99mTc‐stannous fluoride‐labelled‐leucocytes in rats

Tsopelas¹,

Smith²,

Drew³

et al. 2003

Labelled Comp Radiopharmac

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99mTc-Alafosfalin: an antibiotic peptide infection imaging agent

Cited by 36 publications

References 22 publications

Investigation of four 99mTc-labeled bacteriophages for infection-specific imaging

Investigation of four 99mTc-labeled bacteriophages for infection-specific imaging

Evaluation of99mTc-immunoglobulins for imaging infection in the rat

Preparation and biological evaluation of ^99mTc‐stannous fluoride colloid‐labelled‐leucocytes in rats ^99mTc‐stannous fluoride‐labelled‐leucocytes in rats

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99mTc-Alafosfalin: an antibiotic peptide infection imaging agent

Cited by 36 publications

References 22 publications

Investigation of four 99mTc-labeled bacteriophages for infection-specific imaging

Investigation of four 99mTc-labeled bacteriophages for infection-specific imaging

Evaluation of99mTc-immunoglobulins for imaging infection in the rat

Preparation and biological evaluation of 99mTc‐stannous fluoride colloid‐labelled‐leucocytes in rats 99mTc‐stannous fluoride‐labelled‐leucocytes in rats

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Preparation and biological evaluation of ^99mTc‐stannous fluoride colloid‐labelled‐leucocytes in rats ^99mTc‐stannous fluoride‐labelled‐leucocytes in rats