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Imaging Tracer Specific to Bacterial Infections Shows Early Promise

— Maltodextrin-based PET scan agent ID'd early-stage infections in rats

MedpageToday

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It may be possible to distinguish infection from inflammation with maltodextrin imaging agents, according to one rat study looking at these tracers to catch infections early on for implanted cardiac devices.

One such tracer, maltohexaose conjugated with fluorescent dye, accumulated at 1 hour after injection in a model of subclinical device pocket infection in rats (intensity ratio 1.54 versus 1.26 for sterile control versus 1.20 for inflammation model, P<0.05). This observation persisted for over 24 hours, according to W. Robert Taylor, MD, PhD, of Emory University School of Medicine in Atlanta, and colleagues.

Action Points

  • Note that this rat study found that a maltodextrin tracer may be useful in identifying bacterial infection versus inflammation in implanted cardiac devices.
  • Small areas of infection may be below the limit of resolution of most PET scanners, however.

Positron emission tomography (PET) imaging confirmed that another maltodextrin-based probe, 18F fluoro-maltohexaose, was specific to infected areas 30 minutes after injection, Taylor's group reported online in . This was a better result than seen with another radiotracer, 18F fluorodeoxyglucose, which accumulated in both infected and inflamed areas.

"Our results indicate that maltohexaose based imaging probes are potentially useful for the specific and sensitive diagnosis of infections associated with implantable cardiac devices," the researchers concluded, noting that device infection after primary pacemaker or implantable cardioverter defibrillator implantation occurs in about 0.5% of patients and incidence jumps 10-fold after device replacement or upgrade surgery.

"This raises the possibility that in select patients with early stage infection, there exists the possibility to effectively treat the infection with antibiotics without the need to extract the device. In addition, our approach to bacterial imaging could also be used to monitor the efficacy of antibiotic therapy," they suggested. "The impact of this approach on morbidity and mortality as well as the costs associated with infected medical devices could be very significant."

The basis of their analyses came from comparing three groups of male rats implanted with stainless steel mock cardiac devices: ones injected with bacteria, others that got oil of turpentine to induce non-infectious inflammation, and a group receiving neither as control. Two days after receiving these assigned treatments, the imaging agents were injected intravenously and the animals scanned.

Because bacteria ingest maltodextrin quickly, researchers presumed that probes based on this artificial sugar -- often found in sweets such as soda and candy -- would lead straight to infected sites.

"In our experiments, we intentionally performed the in vivo studies using a very mild degree of infection in order to mimic a pre-clinical infection," Taylor and colleagues noted.

However, it is unclear exactly how much bacteria was injected in their experiments, Mohammad Sajadi, MD, of Baltimore's University of Maryland School of Medicine, and colleagues pointed out in an accompanying editorial.

Sajadi's group called 18F-maltodextrin a "plausible specific tracer for bacteria" but cautioned that how well it does depends on the amount of tracer accumulated in a target region, and the spatial resolution of PET.

"If the total number of bacteria is low, or the bacteria are engulfed by leukocytes and unable to access the tracer, then it is possible that the tracer signal may not be high enough to be detected by PET. This is particularly critical, as most of the current non-digital PET machines have a poor spatial resolution of about 6 mm, with associated partial volume effect for small lesions. Although the poor spatial resolution of PET can be compensated by a high local tracer signal, this may not be the case for mild infection with small number of bacteria," they wrote.

Another problem is that heart and lung movements during PET scanning may impede a search for bacteria lodged in cardiac devices, the editorialists added.

"This is an important progress in the field which has eluded clinicians and radiologists for half a century," Sajadi and colleagues wrote. "It is rather premature, however, to predict the ultimate success of this imaging probe in the clinical setting, given the myriad of technical challenges related to the total number of bacteria present at the site of the infection and the spatial resolution of PET. In addition, further testing is needed to validate that the biofilm does not interfere with maltohexaose uptake."

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    Nicole Lou is a reporter for ľֱ, where she covers cardiology news and other developments in medicine.

Disclosures

Authors of the study are listed as inventors of the imaging agents studied in an patent application held by Emory University and the Georgia Institute of Technology.

Sajadi disclosed no relevant conflicts of interest.

Primary Source

JACC: Cardiovascular Imaging

Takemiya K, et al "Novel PET and near infrared imaging probes for the specific detection of bacterial infections associated with cardiac devices" JACC Cardiovasc Imaging 2018.

Secondary Source

JACC: Cardiovascular Imaging

Sajadi MM, et al "Target bacteria-specific 18F-Fluoro-maltohexaose but not FDG PET distinguishes infection from inflammation" JACC Cardiovasc Imaging 2018.