Scintigraphic imaging of bacterial and fungal infection in granulocytopenic rats.
Scintigraphic imaging in granulocytopenic patients can be very useful to detect and localize infections, which often do not show localizing signs and symptoms. We studied the potential of 99mTc-labeled polyethylene glycol (PEG)-coated liposomes and 99mTc-labeled IgG to image bacterial and fungal infection in a granulocytopenic rat model. 67Ga-citrate was used as a reference agent.


METHODS
99mTc-PEG-liposomes, 99mTc-hydrazinonicotinate (HYNIC)-IgG or 67Ga-citrate was administered to granulocytopenic rats with a Staphylococcus aureus abscess or with unilateral invasive pulmonary aspergillosis. Imaging and biodistribution studies were performed.


RESULTS
All agents visualized the S. aureus infection from 1 h after injection onward. However, only with 99mTc-PEG-liposomes and with 99mTc-HYNIC-IgG did activity in the infectious foci increase with time up to 24 h. 99mTc-PEG-liposomes and 99mTc-HYNIC-IgG showed significantly higher accumulation in the infectious focus compared with 67Ga-citrate (1.33+/-0.31 and 1.40+/-0.16 percentage injected dose per gram [%ID/g], respectively, versus 0.31+/-0.04 %ID/g 24 h after injection; P<0.05). At 24 h after injection, abscess-to-muscle ratios were highest for 99mTc-liposomes (72.1+/-19.1), followed by 99mTc-HYNIC-IgG (18.3+/-3.3) and 67Ga-citrate (4.4+/-0.7). In pulmonary aspergillosis, both 99mTc-PEG-liposomes and 99mTC-HYNIC-IgG showed significantly higher uptake in the infected lung than did 67Ga-citrate (3.6+/-0.4 and 8.3+/-0.8 %ID/g, respectively, versus 1.3 %ID/g at 24 h after injection; P<0.05).


CONCLUSIONS
99mTc-PEG-liposomes and 99mTc-HYNIC-IgG performed better than did 67Ga-citrate in the localization of peripheral bacterial infection and fungal infection in the lung in granulocytopenic rats. The high focal uptake and high target-to-nontarget ratios of 99mTc-PEG-liposomes and 99mTc-HYNIC-IgG indicate that both radiopharmaceuticals may become valuable agents to image infection in granulocytopenic patients.
Dams
E T
ET
Department of Nuclear medicine, University Hospital Nijmegen, The Netherlands.
Becker
M J
MJ
Oyen
W J
WJ
Boerman
O C
OC
Storm
G
G
Laverman
P
P
de Marie
S
S
van der Meer
J W
JW
Bakker-Woudenberg
I A
IA
Corstens
F H
FH
D000038:Abscess / Q000150:complications / Q000000981:diagnostic imaging*; D000380:Agranulocytosis / Q000150:complications*; D000818:Animals; D001228:Aspergillosis / Q000150:complications / Q000000981:diagnostic imaging*; D002951:Citrates; D004337:Drug Carriers; D005708:Gallium; D005710:Gallium Radioisotopes; D007074:Immunoglobulin G; D008081:Liposomes; D008172:Lung Diseases, Fungal / Q000150:complications / Q000000981:diagnostic imaging*; D008297:Male; D009135:Muscular Diseases / Q000150:complications / Q000000981:diagnostic imaging; D015609:Organotechnetium Compounds; D011092:Polyethylene Glycols; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000150:complications / Q000000981:diagnostic imaging*; D013667:Technetium
D002951:Citrates; D004337:Drug Carriers; D005710:Gallium Radioisotopes; D007074:Immunoglobulin G; D008081:Liposomes; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C099153:technetium Tc 99m hydrazinonicotinate-IgG; D011092:Polyethylene Glycols; D013667:Technetium; D005708:Gallium; C103850:gallium citrate