Safety, biodistribution, and dosimetry of 99mTc-HYNIC-annexin V, a novel human recombinant annexin V for human application.
99mTc-hydrazinonicotinamido (HYNIC)-annexin V is a novel tracer for in vivo imaging of apoptosis. The present study on humans was performed to investigate the safety of (99m)Tc-HYNIC-annexin V and to quantify the biodistribution and radiation dose.


METHODS
Six healthy, male volunteers participated in the study. A dual-head gamma camera was used to acquire conjugate anterior and posterior views. Imaging started with a transmission scan using a (57)Co-flood source to obtain a map of the local thickness of the volunteer. Approximately 250 MBq of (99m)Tc-HYNIC-annexin V were injected intravenously, directly followed by a 30-min dynamic study. Whole-body scans were obtained at about 30 min, 3 h, 6 h, and 24 h after injection. Organ uptake was determined after correction for background, scatter, and attenuation. The MIRDOSE3.1 program was used to calculate organ-absorbed doses and effective dose. Signs of adverse effects were investigated by monitoring renal and liver function, hematology, blood coagulation, and vital signs (blood pressure, pulse, respiration rate, temperature, and electrocardiogram).


RESULTS
The kidneys accumulated 49.7 +/- 8.1 percentage injected dose (%ID) at 3 h after injection; the liver, 13.1 +/- 1.0 %ID; the red marrow, 9.2 +/- 1.8 %ID; and the spleen, 4.6 +/- 1.6 %ID. More than 90% of the blood activity was cleared with a half-life of 24 +/- 3 min. The biologic half-life of the activity registered over the total body was long (69 +/- 7 h). Excretion of the activity was almost exclusively through the urine (22.5 +/- 3.5 %ID at 24 h), and hardly any activity was seen in the bowel or feces. Absorbed doses were found to be 196 +/- 31 micro Gy/MBq for the kidneys, 41 +/- 12 micro Gy/MBq for the spleen, 16.9 +/- 1.3 micro Gy/MBq for the liver, and 8.4 +/- 0.9 micro Gy/MBq for the red marrow. The effective dose was 11.0 +/- 0.8 micro Sv/MBq, or 2.8 +/- 0.2 mSv for the average injected activity of 250 MBq. No adverse effects were observed.


CONCLUSIONS
(99m)Tc-HYNIC-annexin V is a safe radiopharmaceutical, having a favorable biodistribution for imaging of apoptosis in the abdominal as well as thoracic area with an acceptable radiation dose.
Kemerink
Gerrit J
GJ
Department of Nuclear Medicine, University Hospital Maastricht, Maastricht, The Netherlands. gkk@rdia.azm.nl
Liu
Xuan
X
Kieffer
Davy
D
Ceyssens
Sarah
S
Mortelmans
Luc
L
Verbruggen
Alfons M
AM
Steinmetz
Neil D
ND
Vanderheyden
Jean-Luc
JL
Green
Allan M
AM
Verbeke
Kristin
K
D000328:Adult; D017304:Annexin A5 / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001822:Body Burden; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D015609:Organotechnetium Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011829:Radiation Dosage; D011874:Radiometry / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014915:Whole-Body Counting / Q000379:methods*
D017304:Annexin A5; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; C117287:technetium Tc 99m HYNIC annexin V