Biodistribution of 99mTc-HYNIC-lactadherin in mice--a potential tracer for visualizing apoptosis in vivo.
BACKGROUND
The aim of this study was to establish a radio synthesis of (99m)Tc-HYNIC-lactadherin for in vivo studies and to perform biodistribution analysis studies in mice, comparing (99m)Tc-HYNIC-lactadherin to (99m)Tc-HYNIC-annexin V.


METHODS
The radiochemical purity of (99m)Tc-HYNIC-lactadherin was optimized by varying the amount of SnCl(2) in the synthesis. Furthermore, the need for bovine serum albumin (BSA) as a stabilizing agent was evaluated by following the stability by radiochemical purity measurement with and without the addition of BSA. A total of 24 mice were assigned to groups of 15 and nine mice, respectively. The animals were sacrificed at different time points; 10 min, 60 min, and 180 min.


RESULTS
The synthesis of (99m)Tc-HYNIC-lactadherin for in vivo studies has been optimized to give a stable product without addition of BSA and with a radiochemical purity of more than 95%. Approximately 60% of the injected dose of (99m)Tc-HYNIC-lactadherin was found in the liver and 4-5% could be assigned to kidneys. In contrast, (99m)Tc-HYNIC-annexin V distributes with around 13% and 45% of the injected dose in liver and kidneys, respectively. Over the experimental period (10-180 min) only small distributional changes were observed for both probes.


CONCLUSIONS
In conclusion, the biodistribution of (99m)Tc-HYNIC-lactadherin, a potential new tracer for in vivo quantification of apoptosis, was evaluated. The small renal uptake of (99m)Tc-HYNIC-lactadherin makes it possible to image apoptosis in the kidneys, but the high liver clearance may be a disadvantage during myocardial perfusion.
Falborg
Lise
L
Department of Nuclear Medicine, Aarhus University Hospital, Aarhus Sygehus, Denmark. lisefalb@rm.dk
Waehrens
Lasse N
LN
Alsner
Jan
J
Bluhme
Henrik
H
Frøkiaer
Jørgen
J
Heegaard
Christian W
CW
Horsman
Michael R
MR
Rasmussen
Jan T
JT
Rehling
Michael
M
D000818:Animals; D017304:Annexin A5 / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D005047:Etoposide / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D051379:Mice; D008894:Milk Proteins / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011849:Radioactive Tracers; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects
D017304:Annexin A5; D008894:Milk Proteins; D015609:Organotechnetium Compounds; D011849:Radioactive Tracers; C552083:technetium 99m HYNIC-bovine lactadherin; C117287:technetium Tc 99m HYNIC annexin V; D005047:Etoposide