Radiolabeled annexin V imaging: diagnosis of allograft rejection in an experimental rodent model of liver transplantation.
OBJECTIVE
To assess the value of imaging rejection-induced apoptosis with technetium 99m and annexin V, a human protein-based radiopharmaceutical used in the diagnosis of acute rejection of a liver transplant, in a well-characterized rodent model of orthotopic liver transplantation.


METHODS
99mTc-radiolabeled annexin V was intravenously administered to six allografted (immunologically mismatched) and five isografted (immunologically matched) recipient rats on days 2, 4, and 7 after orthotopic liver transplantation. Animals were imaged 1 hour after injection of 0.2-2.0 mCi (8.0-74.0 MBq) of radiolabeled annexin V by use of clinical nuclear scintigraphic equipment.


RESULTS
All animals in the allografted group demonstrated marked increases of 55% and 97% above the activity in the isografted group in hepatic uptake of annexin V on days 4 and 7, respectively. Severe acute rejection was histologically detected in all allografted livers on day 7. There was no histologic evidence of acute rejection in isografted animals. Dynamic hepatobiliary imaging with 99mTc and mebrofenin, an iminodiacetic acid derivative, demonstrated no correlation with the presence or absence of acute rejection or with annexin V uptake.


CONCLUSIONS
Noninvasive imaging with radiolabeled annexin V is more sensitive and specific than imaging with 99mTc-mebrofenin in the diagnosis of acute rejection of a liver transplant.
Ogura
Y
Y
Dept of Surgery, Stanford University School of Medicine, Lucile Salter Packard Children's Hospital, Palo Alto, CA 94304, USA.
Krams
S M
SM
Martinez
O M
OM
Kopiwoda
S
S
Higgins
J P
JP
Esquivel
C O
CO
Strauss
H W
HW
Tait
J F
JF
Blankenberg
F G
FG
D000208:Acute Disease; D000814:Aniline Compounds; D000818:Animals; D017304:Annexin A5; D005998:Glycine; D006084:Graft Rejection / Q000000981:diagnostic imaging* / Q000276:immunology; D007098:Imino Acids; D008099:Liver / Q000000981:diagnostic imaging; D016031:Liver Transplantation / Q000276:immunology; D008297:Male; D015609:Organotechnetium Compounds; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D012680:Sensitivity and Specificity; D013668:Technetium Tc 99m Aggregated Albumin
D000814:Aniline Compounds; D017304:Annexin A5; D007098:Imino Acids; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D013668:Technetium Tc 99m Aggregated Albumin; C098309:technetium Tc 99m hydrazino nicotinyl-human serum albumin; C034837:technetium Tc 99m mebrofenin; D005998:Glycine