Pathogen-Specific Bacterial Imaging in Nuclear Medicine

Abstract

When serious infections are suspected, patients are often treated empirically with broad-spectrum antibiotics while awaiting results that provide information on the bacterial class and species causing the infection, as well as drug susceptibilities. For deep-seated infections, these traditional diagnostic techniques often rely on tissue biopsies to obtain clinical samples which can be expensive, dangerous, and has the potential of sampling bias. Moreover, these procedures and results can take several days and may not always provide reliable information. This combination of time and effort required for proper antibiotic selection has become a barrier leading to indiscriminate broad-spectrum antibiotic use. Exposure to nosocomial infections and indiscriminate use of broad-spectrum antibiotics are responsible for promoting bacterial drug-resistance leading to substantial morbidity and mortality, especially in hospitalized and immunosuppressed patients. Therefore, early diagnosis of infection and targeted antibiotic treatments are urgently needed to reduce morbidity and mortality caused by bacterial infections worldwide. Reliable pathogen-specific bacterial imaging techniques have the potential to provide early diagnosis and guide antibiotic treatments.

An update on radiotracer development for molecular imaging of bacterial infections

“…From preclinical studies in vivo it has been shown that 99m Tc-UBI 29-41 (coordination unknown) and 99m Tc-HYNIC UBI 29-41 (Scheme 4) accumulated specifically in infected tissues with abscessto-muscle ratios between 2 and 3 [14,56,57]. Both recently developed PET analogues 68 Ga-NOTA-UBI 29-41 [12,[58][59][60][61] and 68 Ga-NOTA-UBI 31-38 [62] showed comparable uptake characteristics in infected thigh muscles in mice and rabbits. However, UBI 29-41 also accumulated in infections with the yeast C. albicans [63], which reduces specificity of this tracer for imaging of bacterial infections alone.…”

“…This review is an update of our earlier review published in 2013 [14], as well as other thematic reviews [12,[15][16][17][18][19][20][21].…”

“…Molecular imaging solutions-as in oncology-have been shown to aid non-invasive diagnosis of bacterial infections in an early (non-disruptive) state [11]. Examples of these techniques are summarised in Table 1 and includes radiotracers such as 67 Ga-citrate, 99m Tc-labelled autologous leukocytes and [ 18 F]-FDG, which are commonly used in western clinical practise [9,12,13]. For the current review, the PubMed/ MEDLINE and Embase (OvidSP) literature databases were systematically searched for publications on SPECT and PET on specific imaging of bacterial using specific guidelines with MeSH-terms, truncations, and completion using crossreferences.…”

Positron Emission Tomography Imaging with 2-[18F]F-p-Aminobenzoic Acid Detects Staphylococcus aureus Infections and Monitors Drug Response

“…Previous efforts to develop pathogen-specific PET imaging methods have classically focused on radiolabeling existing antibiotics or antimicrobial peptides. 7 − 10 While this approach builds upon known chemistry and target interaction, both antibiotics and antimicrobial peptides are pharmacologically active and may paradoxically destroy the bacteria and interfere with the signal. Also, these compounds lack the capacity for signal amplification that could be achieved with agents that accumulate in bacteria.…”

Radiosynthesis and validation of [Carboxy‐11C]4‐Aminobenzoic acid ([11C]PABA), a PET radiotracer for imaging bacterial infections

“…Given that current imaging techniques remain nonspecific for imaging bacterial infections, there remains a need for developing bacteria-specific radiotracers that identify a wide range of clinically relevant bacteria with high sensitivity. 1 After approximately 1000 small molecules were screened, several promising candidates were identified for radiolabeling and imaging infections, including paraaminobenzoic acid (4-aminobenzoic acid; PABA). In tritiated form, PABA was demonstrated to accumulate in a broad class of bacteria including Gram-positives, Gramnegatives (as well as Pseudomonas spp.…”