The tripeptide formyl-Met-Leu-Phe (fMLF) is a prototype of N-formylated chemotactic peptides for neutrophils owing to its ability to bind and activate the G protein-coupled formyl peptide receptor (FPR). Here, we developed an 18F-labeled fMLF derivative targeting FPR as a positron emission tomography (PET) imaging probe for bacterial infections

Infectious diseases still majorly account for the cause of death, and they require social measures. Bacteriological or serological tests are undoubtedly the gold standard for diagnosing infectious diseases. However, these tests require time to obtain results.

Furthermore, although these tests prove the existence of bacteria, it is impossible to distinguish which part of the living body is infected. Therefore, the local diagnosis of infectious diseases using diagnostic imaging has been clinically used for a long time.

Presently, X-Ray, CT, and MRI are used for diagnostic imaging for infectious diseases, but none of them specifically cater to the spread of inflammatory lesions associated with infection; thus, if the inflammatory foci do not enlarge, accurate diagnosis presents a challenge.

Therefore, nuclear medicine techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) that can obtain functional information have attracted attention.

Nuclear medicine techniques

Scintigraphy and SPECT using autologous leukocytes labeled with 111In or 99mTc are considered the gold standard for diagnosing infections. However, there are certain drawbacks as leukocytes obtained from the blood sample must be labeled ex vivo. This process, performed in a specialized laboratory, raises the potential risk of infection of both the patient and laboratory personnel.

67Ga-citrate and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) have been in use as SPECT and PET imaging probes for the detection of inflammatory and infectious conditions.6–8 However, none of these probes are specific for bacterial infections. Hence, novel safety and specific imaging probes for the early detection of bacterial infections are needed.9

The study demonstrates that the fMLF derivative fMLFXYk(FB)k (X?=?Nle) has a high affinity for FPR (Ki?=?0.62?±?0.13?nM). The radiochemical yield and purity of [18F]fMLFXYk(FB)k were 16% and >96%, respectively.

The in vivo biodistribution study showed that [18F]fMLFXYk(FB)k uptake was higher in the bacterially infected region than in the non-infected region. We observed the considerably higher infection-to-muscle ratio of 4.6 at 60?min after [18F]fMLFXYk(FB)k injection. Furthermore, small-animal PET imaging studies suggested that [18F]fMLFXYk(FB)k uptake in the bacterially infected region was clearly visualized 60?min after injection.