Imaging cyclophosphamide-induced intramedullary apoptosis in rats using 99mTc-radiolabeled annexin V.
Intramedullary apoptosis of hematopoietic tissue is believed to play a major role in the pathophysiology of myelodysplastic syndrome. Annexin V, a specific marker of the early to intermediate phases of apoptosis, has been applied to the in vitro study of bone marrow aspirates. A noninvasive measure of intramedullary apoptosis in vivo that could serially monitor the clinical progression of myelodysplastic syndrome may be helpful.


METHODS
We used 99mTc-radiolabeled annexin V and radionuclide gamma camera imaging to serially study the sites, extent, and severity of intramedullary apoptosis induced by cyclophosphamide treatment.


RESULTS
Intravenously administered radiolabeled annexin V localized preferentially in the femur, pelvis, vertebrae, and spleen; increased uptake in these organs was easily visualized as early as 8 h after injection of 100 mg/kg cyclophosphamide in 8- to 10-wk-old animals. Higher doses of cyclophosphamide (150 mg/kg) in animals of the same age increased annexin V uptake in the bone marrow and splenic tissue and delayed recovery of these organs as seen histologically compared with lower doses. Older animals, 5-6 mo old, showed a slower response to cyclophosphamide treatment and delayed recovery of bone marrow and splenic tissues.


CONCLUSIONS
Radiolabeled annexin V can be used to detect and directly quantify the degree of intramedullary and splenic apoptosis in a noninvasive fashion using current clinical radionuclide imaging equipment. Annexin V imaging may be useful clinically in the diagnosis and management of myelodysplastic syndrome.
Blankenberg
F G
FG
Division of Pediatric Radiology, Lucile Salter Packard Children's Hospital, Stanford, California, USA.
Naumovski
L
L
Tait
J F
JF
Post
A M
AM
Strauss
H W
HW
D000375:Aging; D000818:Animals; D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects*; D001853:Bone Marrow / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000473:pathology; D003520:Cyclophosphamide / Q000494:pharmacology*; D015902:Gamma Cameras; D008297:Male; D009190:Myelodysplastic Syndromes / Q000000981:diagnostic imaging; D015609:Organotechnetium Compounds; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology
D017304:Annexin A5; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C117287:technetium Tc 99m HYNIC annexin V; D003520:Cyclophosphamide