Detecting infection and inflammation with technetium-99m-labeled Stealth liposomes.
The performance of 99mTc Stealth liposomes was investigated in various rat models.


METHODS
Preformed polyethyleneglycol-containing liposomes with encapsulated reduced glutathione, were radiolabeled using the lipophilic 99mTc-HMPAO. The labeled liposomes were intravenously administered to rats with focal S. aureus or E. coli infection, or turpentine-induced inflammation. For comparison, Tc-99m-nanocolloid- and 99mTc-labeled nonspecific IgG were tested. In rats with Pneumocystis carinii pneumonia (PCP), Tc-99m-liposomes were directly compared to In-111 labeled nonspecific IgG.


RESULTS
Technetium-99m-liposomes accumulated in the infectious and inflammatory muscle foci over 24 hr (0.59% injected dose per gram tissue (%ID/g) for S. aureus; 1.18 %ID/g for turpentine). Abscess-to-muscle ratios increased to values as high as 24.0, 41.7 and 44.5 for the respective models at 24 hr postinjection. Technetium-99m-liposomes visualized the foci as early as 1 hr postinjection. Technetium-99m-IgG visualized S. aureus infection, but abscess-to-muscle ratios and abscess uptake at the later time points were significantly lower. Technetium-99m-nanocolloid failed to visualize any of the muscle foci. In PCP however, 99mTc-liposomes did not show preferential localization in the infection. The control agent 111In-IgG showed a significant, two-fold increase in lung uptake.


CONCLUSIONS
Technetium-99m-Stealth liposomes preferentially accumulated in abscesses, leading to very high target-to-nontarget ratios. This property appears to be related to a process based on uptake of long-circulating particles. In a specific type of infection, i.c. PCP, 99mTc-liposomes did not accumulate in diseased lung tissue, thus mimicking the in vivo behavior of labeled leukocytes.
Oyen
W J
WJ
Department of Nuclear Medicine, University Hospital Nijmegen, The Netherlands.
Boerman
O C
OC
Storm
G
G
van Bloois
L
L
Koenders
E B
EB
Claessens
R A
RA
Perenboom
R M
RM
Crommelin
D J
DJ
van der Meer
J W
JW
Corstens
F H
FH
D000038:Abscess / Q000000981:diagnostic imaging*; D000818:Animals; D004927:Escherichia coli Infections / Q000000981:diagnostic imaging*; D005260:Female; D007074:Immunoglobulin G; D007205:Indium Radioisotopes; D007249:Inflammation / Q000000981:diagnostic imaging*; D008081:Liposomes; D008297:Male; D015609:Organotechnetium Compounds; D010091:Oximes; D011020:Pneumonia, Pneumocystis / Q000000981:diagnostic imaging*; D016719:Radioimmunodetection / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging*; D013668:Technetium Tc 99m Aggregated Albumin; D019690:Technetium Tc 99m Exametazime; D014018:Tissue Distribution
D007074:Immunoglobulin G; D007205:Indium Radioisotopes; D008081:Liposomes; D015609:Organotechnetium Compounds; D010091:Oximes; D013668:Technetium Tc 99m Aggregated Albumin; C079358:technetium TC 99m polyclonal IgG; C083602:technetium Tc 99m nanocolloid; D019690:Technetium Tc 99m Exametazime