TY - JOUR
T1 - [68Ga]Ga-Schizokinen, a Potential Radiotracer for Selective Bacterial Infection Imaging
AU - Akter, Asma
AU - Firth, George
AU - Darwesh, Afnan M.F.
AU - Cooper, Margaret S.
AU - Chuljerm, Hataichanok
AU - Cilibrizzi, Agostino
AU - Blower, Philip J.
AU - Hider, Robert C.
AU - Lyons, Oliver
AU - Schelenz, Silke
AU - Mehra, Varun
AU - Abbate, Vincenzo
N1 - Publisher Copyright:
© 2024 The Authors. Published by American Chemical Society.
PY - 2024/8/9
Y1 - 2024/8/9
N2 - Gallium-68-labeled siderophores as radiotracers have gained interest for the development of in situ infection-specific imaging diagnostics. Here, we report radiolabeling, in vitro screening, and in vivo pharmacokinetics (PK) of gallium-68-labeled schizokinen ([68Ga]Ga-SKN) as a new potential radiotracer for imaging bacterial infections. We radiolabeled SKN with ≥95% radiochemical purity. Our in vitro studies demonstrated its hydrophilic characteristics, neutral pH stability, and short-term stability in human serum and toward transchelation. In vitro uptake of [68Ga]Ga-SKN by Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and S. epidermidis, but no uptake by Candida glabrata, C. albicans, or Aspergillus fumigatus, demonstrated its specificity to bacterial species. Whole-body [68Ga]Ga-SKN positron emission tomography (PET) combined with computerized tomography (CT) in healthy mice showed rapid renal excretion with no or minimal organ uptake. The subsequent ex vivo biodistribution resembled this fast PK with rapid renal excretion with minimal blood retention and no major organ uptake and showed some dissociation of the tracer in the urine after 60 min postinjection. These findings warrant further evaluation of [68Ga]Ga-SKN as a bacteria-specific radiotracer for infection imaging.
AB - Gallium-68-labeled siderophores as radiotracers have gained interest for the development of in situ infection-specific imaging diagnostics. Here, we report radiolabeling, in vitro screening, and in vivo pharmacokinetics (PK) of gallium-68-labeled schizokinen ([68Ga]Ga-SKN) as a new potential radiotracer for imaging bacterial infections. We radiolabeled SKN with ≥95% radiochemical purity. Our in vitro studies demonstrated its hydrophilic characteristics, neutral pH stability, and short-term stability in human serum and toward transchelation. In vitro uptake of [68Ga]Ga-SKN by Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and S. epidermidis, but no uptake by Candida glabrata, C. albicans, or Aspergillus fumigatus, demonstrated its specificity to bacterial species. Whole-body [68Ga]Ga-SKN positron emission tomography (PET) combined with computerized tomography (CT) in healthy mice showed rapid renal excretion with no or minimal organ uptake. The subsequent ex vivo biodistribution resembled this fast PK with rapid renal excretion with minimal blood retention and no major organ uptake and showed some dissociation of the tracer in the urine after 60 min postinjection. These findings warrant further evaluation of [68Ga]Ga-SKN as a bacteria-specific radiotracer for infection imaging.
KW - bacterial infections
KW - diagnostics
KW - gallium-68-labeled siderophores
KW - infection imaging
KW - PET/CT
KW - radiotracer
UR - http://www.scopus.com/inward/record.url?scp=85198957452&partnerID=8YFLogxK
U2 - 10.1021/acsinfecdis.4c00067
DO - 10.1021/acsinfecdis.4c00067
M3 - Article
C2 - 39012184
AN - SCOPUS:85198957452
SN - 2373-8227
VL - 10
SP - 2615
EP - 2622
JO - ACS Infectious Diseases
JF - ACS Infectious Diseases
IS - 8
ER -