Myocardial kinetics of 99m technetium-Q agents: studies in isolated cardiac myocyte, isolated perfused rat heart, and canine regional myocardial ischemia models.
OBJECTIVE
Based on reports of high cellular uptake and low plasma binding of nonreducible mixed ligand Tc(III) cations (Q complexes) and high linear uptake versus blood flow of 99mTc-Q3 in canine hearts, the authors hypothesized that the two Q complexes, 99mTc-Q63 and 99mTc-Q64, would have high cell uptake and better differentiation between ischemic and nonischemic myocardium compared with other 99mTc-based compounds.


METHODS
Uptake and retention kinetics of 99mTc-Q63 and 99mTc-Q64 were measured in isolated rat cardiac myocytes, isolated perfused rat hearts, and intact canines and compared with previously reported Q-based compounds, a clinically available 99mTc perfusion agent (sestamibi), and 201Tl.


RESULTS
Uptake of Q63, Q64, and sestamibi by isolated cardiac myocytes was similar. Maximum extraction (Emax) of Q64 by isolated perfused rat hearts was greatest among the 99mTc agents (P < 0.02), but net extraction (Enet) of Q64 was not different from Q63 or sestamibi 3 minutes after tracer injection. By 15 minutes, 201Tl Enet was lower than Q63, Q64, and sestamibi (P < 0.05). Among 99mTc agents, the uptake versus flow of Q3, Q63, and Q64 by canine heart was superior to Q12 and sestamibi (P < 0.05).


CONCLUSIONS
The activity of Q63 and Q64 in the myocardium is related to actual myocardial blood flow over a broad, clinically relevant range of flows. The ischemic-to-normal zone activity distributions of Q63 and Q64 approximate actual flow in a manner more like that of 201Tl than sestamibi or Q12. These results provide a rational foundation in support of further evaluation of Q63 and Q64 in humans.
McGoron
A J
AJ
Department of Radiology, University of Cincinnati College of Medicine, Ohio 45267-0577, USA.
Biniakiewicz
D
D
Millard
R W
RW
Kumar
A
A
Kennedy
S C
SC
Roszell
N J
NJ
Gabel
M
M
Huth
C
C
Walsh
R A
RA
Gerson
M C
MC
D000208:Acute Disease; D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004285:Dogs; D006321:Heart / Q000000981:diagnostic imaging*; D008297:Male; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D010477:Perfusion / Q000379:methods; D010720:Phosphines / Q000493:pharmacokinetics*; D011865:Radioisotope Dilution Technique; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017256:Technetium Tc 99m Sestamibi / Q000493:pharmacokinetics; D013997:Time Factors
D015609:Organotechnetium Compounds; D010720:Phosphines; D019275:Radiopharmaceuticals; C081212:technetium Tc 99m Q3; C112545:technetium Tc 99m Q4; D017256:Technetium Tc 99m Sestamibi