(68)Ga-DOTAVAP-P1 PET imaging capable of demonstrating the phase of inflammation in healing bones and the progress of infection in osteomyelitic bones.
OBJECTIVE
Differentiation between bacterial infection and nonbacterial inflammation remains a diagnostic challenge. Vascular adhesion protein 1 (VAP-1) is a human endothelial protein whose cell surface expression is induced under inflammatory conditions, thus making it a highly promising target molecule for studying inflammatory processes in vivo. We hypothesized that positron emission tomography (PET) with gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N',N'',N''',N''''-tetraacetic acid-peptide targeted to VAP-1 ((68)Ga-DOTAVAP-P1) could be feasible for imaging the early inflammatory and infectious processes in healing bones.


METHODS
Thirty-four Sprague-Dawley rats with diffuse Staphylococcus aureus tibial osteomyelitis and 34 rats with healing cortical bone defects (representing the inflammation stage of healing) were PET imaged using (68)Ga-DOTAVAP-P1 as a tracer. In addition, peripheral quantitative computed tomography and conventional radiography were performed. Bone samples for quantitative bacteriology and specimens were also processed for histomorphometry of inflammatory and infectious reactions.


RESULTS
PET imaging showed an uptake of (68)Ga-DOTAVAP-P1 in both the osteomyelitic bones and the healing cortical bone defects during the first 36 h after surgery. Thereafter, only the osteomyelitic tibias were delineated by PET. The osteomyelitic and control animals showed a similar uptake of the (68)Ga-DOTAVAP-P1 at 24 h, whereas a significant difference was observed at 7 days (p < 0.0001).


CONCLUSIONS
The current study showed that PET imaging with the new (68)Ga-DOTAVAP-P1 is capable of accurately demonstrating the phase of inflammation in healing bones and the progress of bacterial infection in osteomyelitic bones. Consequently, this novel imaging agent allowed for the differentiation of bone infection due to S. aureus and normal bone healing as soon as 7 days after onset.
Lankinen
Petteri
P
Orthopaedic Research Unit, Department of Orthopaedic Surgery and Traumatology, University of Turku, Turku, Finland.
Mäkinen
Tatu J
TJ
Pöyhönen
Tiina A
TA
Virsu
Pauliina
P
Salomäki
Satu
S
Hakanen
Antti J
AJ
Jalkanen
Sirpa
S
Aro
Hannu T
HT
Roivainen
Anne
A
D000818:Animals; D018450:Disease Progression; D005710:Gallium Radioisotopes; D008297:Male; D009942:Organometallic Compounds; D010000:Osteitis / Q000000981:diagnostic imaging*; D010019:Osteomyelitis / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging*
D005710:Gallium Radioisotopes; D009942:Organometallic Compounds