Interaction of technetium-99m-N-NOET with blood elements: potential mechanism of myocardial redistribution.
Technetium-99m-N-NOET is a new 99mTc-labeled, neutral cardiac perfusion imaging agent which has been shown to undergo apparent redistribution in animal models and in humans. The purpose of this study was to investigate the interaction of 99mTcN-NOET with red blood cells (RBCs) and to determine the effects of these interactions on myocardial uptake and clearance of 99mTcN-NOET.


METHODS
After bolus administration, myocardial 99mTcN-NOET clearance was monitored for 1 hr using a sodium iodide detector in 22 isolated, buffer-perfused rat hearts. Hearts were perfused as follows: seven controls with Krebs-Henseleit (KH) buffer (Group 1), five hearts with KH containing RBCs (Group 2), five hearts with KH containing RBCs and albumin (Group 3), five hearts with KH containing RBCs and dextran (Group 4). In a separate protocol, RBCs were incubated in 99mTcN-NOET and then perfused through five hearts (Group 5).


RESULTS
Technetium-99m-N-NOET myocardial uptake (%ID) was significantly lower in all RBC groups (RBCs = 5.0% +/- 1.7%; RBCs + albumin = 8.2% +/- 2.1%; RBCs + dextran = 4.0% +/- 0.8%; incubated RBCs = 8.8% +/- 1.5%) compared with controls (72.2% +/- 2.8%; p < 0.05). Retention (99.4% +/- 0.6%) was near linear in the KH control group with virtually no fractional clearance at 60 min. Retention in groups whose perfusates contained RBCs (RBCs = 62.2 +/- 4.2%; RBCs + albumin = 29.9 +/- 4.3%; RBCs + dextran = 69.3 +/- 3.6%) were all significantly lower than control. Addition of albumin to RBC perfusate resulted in significantly lower retention (29.9% +/- 4.3%; p < 0.01) than was observed in RBC perfusate alone (62.2% +/- 4.2%). Substitution of dextran for albumin produced retention similar to RBCs alone (69.3% +/- 3.6%; p = ns). In a separate protocol, RBC binding of 99mTcN-NOET was high (64.4% +/- 8.6%) in triple-washed RBCs. Technetium-99m-N-NOET bound to RBCs was subsequently extracted from red cells by the myocardium when those cells were infused into hearts.


CONCLUSIONS
Technetium-99m-N-NOET has high binding affinity to blood elements and transfers bidirectionally between myocardium and blood. The interaction of 99mTcN-NOET with blood elements represents a potential mechanism of redistribution.
Johnson
G
G
William K. Warren Medical Research Institute, University of Oklahoma Health Sciences Center, Tulsa 74136, USA.
Nguyen
K N
KN
Pasqualini
R
R
Okada
R D
RD
D000818:Animals; D004912:Erythrocytes / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism*; D013859:Thiocarbamates / Q000493:pharmacokinetics*
D015609:Organotechnetium Compounds; D012709:Serum Albumin; D013859:Thiocarbamates; C093922:technetium Tc 99m, bis(N-ethoxy-N-ethyldithiocarbamato)nitrido-