Radionuclide Imaging of Infection: In Search of the Grail

Palestro, Christopher J.

doi:10.2967/jnumed.108.058297

Cited by 45 publications

(36 citation statements)

References 16 publications

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“…We built on past efforts to develop an imaging tool that specifically identifies live bacteria without confounding signal from sterile inflammation or cancer. Bacteria, from a different phylogenetic domain, should have molecular imaging targets more diverse and accessible for imaging pathology than, for example, a cancer cell, where there are just a few genetic mutations to differentiate that cancer cell from normal host tissues (4). With this in mind, we revisited the idea of an antibiotic PET radiotracer because of the small-molecule characteristics of the antibiotic and the sensitivity and spatial localization of PET.…”

Section: Discussionmentioning

confidence: 99%

“…With this in mind, we revisited the idea of an antibiotic PET radiotracer because of the small-molecule characteristics of the antibiotic and the sensitivity and spatial localization of PET. It is surprising, perhaps, that this advancement comes at a time when interest in antibiotic radiotracers for imaging infection has waned, especially after tracer derivatives of ciprofloxacin have had mixed clinical results (4,19). Further in vitro studies with quinolone radiotracers showed binding to heat-killed bacteria and nonspecific uptake in the presence of excess unlabeled compound, tempering enthusiasm for clinical use (20,21).…”

Section: Discussionmentioning

confidence: 99%

“…Given these clear potential uses, past efforts have focused largely on nuclear techniques based on radiotracers derived from peptides, antibiotics, and sugars due to the required sensitivity needed for identifying bacteria (3,4). Still, no bacterial imaging agent is routinely used clinically, and among the previously developed agents many are not sufficiently broad spectrum to provide strong negative and positive predictive values to inform clinical decision making.…”

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confidence: 99%

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Bacterial infection imaging with [ ¹⁸ F]fluoropropyl-trimethoprim

Sellmyer

Lee

Hou

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

113

110

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There is often overlap in the diagnostic features of common pathologic processes such as infection, sterile inflammation, and cancer both clinically and using conventional imaging techniques. Here, we report the development of a positron emission tomography probe for live bacterial infection based on the small-molecule antibiotic trimethoprim (TMP). [18F]fluoropropyl-trimethoprim, or [18F]FPTMP, shows a greater than 100-fold increased uptake in vitro in live bacteria (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) relative to controls. In a rodent myositis model, [18F]FPTMP identified live bacterial infection without demonstrating confounding increased signal in the same animal from other etiologies including chemical inflammation (turpentine) and cancer (breast carcinoma). Additionally, the biodistribution of [18F]FPTMP in a nonhuman primate shows low background in many important tissues that may be sites of infection such as the lungs and soft tissues. These results suggest that [18F]FPTMP could be a broadly useful agent for the sensitive and specific imaging of bacterial infection with strong translational potential.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Bacterial infection imaging with [ ¹⁸ F]fluoropropyl-trimethoprim

Sellmyer

Lee

Hou

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

113

110

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“…Inf ectious diseases have a major impact on global morbidity and mortality despite advances in both diagnosis and treatment (1). The early identification and correct diagnosis of an active infection is crucial to its effective control or adequate treatment.…”

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confidence: 99%

Preclinical Evaluation of ⁶⁸Ga-Labeled 1,4,7-Triazacyclononane-1,4,7-Triacetic Acid-Ubiquicidin as a Radioligand for PET Infection Imaging

et al. 2014

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Antimicrobial peptides such as ubiquicidin (UBI) are believed to differentiate between mammalian and bacterial or fungal cells. 99m Tc-UBI29-41 was previously tested for detecting infection in humans using SPECT. For the present study, the UBI fragment UBI29-41 (TGRAKRRMQYNRR) was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA), radiolabeled with 68 Ga, and investigated in a rabbit infection model. Methods: 68 Ga was obtained from a 1.85-GBq 68 Ge/ 68 Ga generator. New Zealand White rabbits were anesthetized with ketamine/medetomidine before tracer administration and placed in a clinical PET/CT scanner. 68 Ga-1,4,7-triazacyclononane-1,4,7-triacetic-acid-ubiquicidin29-41 ( 68 Ga-NOTA-UBI29-41) was formulated in saline solution, and 101 6 41 MBq were administered intravenously. The tracer distribution was studied by PET/CT imaging in animals (a) that were healthy, (b) bearing muscular Staphylococcus aureus infections and turpentine oilinduced muscular inflammations, and (c) bearing ovalbumin-induced lung inflammations. Static PET/CT imaging was performed at different time intervals up to 120 min after injection. For calculation of target-to-nontarget ratios, standardized uptake values were normalized against healthy thigh muscle, representing nontargeted tissue. Results: PET/CT images of healthy animals showed predominant distribution in the kidneys, liver, and bladder; heart and spleen showed moderate, declining uptake, only. The biologic half-life in blood was 29 min. Urinary accumulation of 68 Ga-NOTA-UBI29-41 peaked at 3.8 6 0.91 percentage injected dose per gram (%ID) at 120 min, and 88 6 5.2 %ID was recovered in total urine. 68 Ga-NOTA-UBI29-41 imaging in (b) selectively visualized the muscular infection site and was differentiated from sterile inflammatory processes. Standardized uptake value ratios for muscles (infected/ inflamed) were 2.9 6 0.93, 2.9 6 0.50, 3.5 6 0.86, and 3.8 6 0.90 at 5, 30, 60, and 90 min after injection, respectively. Rabbit lungs with asthma showed insignificant uptake. Conclusion: 68 Ga-NOTA-UBI29-41 was strongly localized in bacteria-infected areas and minimally detected in a sterile inflammation area in rabbit muscles. The findings propose this compound to be an excellent first-line PET/CT tracer to allow the distinguishing of infection from inflammation.

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“…Nuclear medicine has played an important role in the evaluation of patients suspected of harboring infection for decades, including the use of 99m Tc-methylene diphosphonate (MDP), 67 Gallium-citrate ( 67 Ga), and 111 In-oxine-and 99m Tc-hexamethylpropyleneamine oxime (HMPAO)-labeled autologous leukocytes [2,9,10]. However, studies investigating the application of nuclear medicine to fever of unknown origin or occult sepsis in critically ill patients are limited [6,7,11].…”

Section: Introductionmentioning

confidence: 99%

Role of Gallium-67 scintigraphy in the evaluation of occult sepsis in the medical ICU

et al. 2011

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Patients in intensive care units (ICUs) frequently have multiple infections or persistent fever despite management. The aim of this study was to evaluate the diagnostic contribution of gallium-67 scintigraphy in ICU patients with suspected occult sepsis. One hundred and seventeen patients (>18 years) who had undergone gallium-67 scintigraphy in the ICU of our medical center over a 3-year period were retrospectively reviewed and analyzed. Patients were categorized into Group 1 (n = 84), those with a known infectious source, but who still had persistent fever or sepsis despite antibiotic treatment or abscess drainage; or Group 2 (n = 33), those without an evident infectious source after clinical, physical, and imaging studies. Among the 117 patients, 19 (16.2%) had a new diagnosis. In Group 1, 12 patients (14%) had a new infection, including pneumonia (4 patients), bed sore infection (2 patients), pulmonary tuberculosis (2 patients), leg cellulitis (1 patient), psoas muscle abscess (1 patient), osteomyelitis (1 patient), and infective endocarditis (1 patient). In Group 2, seven patients (21.2%) had a new infectious source, including septic arthritis (3 patients), osteomyelitis (2 patients), neck abscess (1 patient), and cholecystitis (1 patient). Significant differences were not observed between patients with positive and negative findings on gallium-67 scintigraphy in characteristics, underlying diseases, laboratory data, and outcomes. Gallium-67 scintigraphy helped to detect new or additional infectious sites, particularly bone, joint, and soft tissues. However, differences in hospital stay and mortality were not observed between patients with positive and negative findings.

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Radionuclide Imaging of Infection: In Search of the Grail

Cited by 45 publications

References 16 publications

Bacterial infection imaging with [ ¹⁸ F]fluoropropyl-trimethoprim

Bacterial infection imaging with [ ¹⁸ F]fluoropropyl-trimethoprim

Preclinical Evaluation of ⁶⁸Ga-Labeled 1,4,7-Triazacyclononane-1,4,7-Triacetic Acid-Ubiquicidin as a Radioligand for PET Infection Imaging

Role of Gallium-67 scintigraphy in the evaluation of occult sepsis in the medical ICU

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Radionuclide Imaging of Infection: In Search of the Grail

Cited by 45 publications

References 16 publications

Bacterial infection imaging with [ 18 F]fluoropropyl-trimethoprim

Bacterial infection imaging with [ 18 F]fluoropropyl-trimethoprim

Preclinical Evaluation of 68Ga-Labeled 1,4,7-Triazacyclononane-1,4,7-Triacetic Acid-Ubiquicidin as a Radioligand for PET Infection Imaging

Role of Gallium-67 scintigraphy in the evaluation of occult sepsis in the medical ICU

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Bacterial infection imaging with [ ¹⁸ F]fluoropropyl-trimethoprim

Bacterial infection imaging with [ ¹⁸ F]fluoropropyl-trimethoprim

Preclinical Evaluation of ⁶⁸Ga-Labeled 1,4,7-Triazacyclononane-1,4,7-Triacetic Acid-Ubiquicidin as a Radioligand for PET Infection Imaging