99mTc-HL91. Effects of low flow and hypoxia on a new ischemia-avid myocardial imaging agent.
BACKGROUND
99mTc-HL91 is a potential imaging agent that has demonstrated increased uptake in hypoxic tumor cells. The purpose of this study was to determine if 99mTc-HL91 demonstrates increased uptake and retention in ischemic and hypoxic myocardium.


RESULTS
99mTc-HL91 (11.1 MBq) was infused over 10 minutes, followed by a 60-minute clearance phase. Activity was monitored by using an NaI detector. Three groups were studied using Krebs-Henseleit buffer (KH): controls (12 mL/min, n = 6), low-flow ischemic (1 mL/min, n = 7), and hypoxic (12 mL/min, n = 8). Two groups were perfused with KH, red blood cells, and albumin: controls (6 mL/min, n = 6) and low-flow ischemic (0.5 mL/min, n = 6). For the KH hearts, the 99mTc-HL91 peak uptake progressively increased from control (6.3 +/- 0.5 microCi, mean +/- SEM) to hypoxic (9.1 +/- 1.0 microCi) to low flow (44.0 +/- 2.6 microCi; P < .01). The peak uptake low-flow/control ratio was 7:1. Final retention increased progressively from control (0.8 +/- 0.1 microCi) to hypoxic (2.9 +/- 0.5 muCi) to low flow (10.9 +/- 1.3 microCi; P < .01). The final low-flow/control activity ratio was 13.6:1. Similar results were observed in the red blood cell-perfused control and low-flow groups.


CONCLUSIONS
This study introduces a new myocardial "hot spot" imaging agent, 99mTc-HL91. This agent demonstrates increased myocardial uptake and retention in hypoxic and low-flow ischemic models. Further in vivo imaging studies are warranted to determine the clinical potential of this agent.
Okada
R D
RD
William K. Warren Medical Research Institute, University of Oklahoma Health Sciences Center, Tulsa 74136, USA.
Johnson
G
G
Nguyen
K N
KN
Edwards
B
B
Archer
C M
CM
Kelly
J D
JD
D000818:Animals; D015687:Cell Hypoxia; D003287:Contrast Media / Q000493:pharmacokinetics*; D003326:Coronary Circulation; D003402:Creatine Kinase / Q000097:blood; D015902:Gamma Cameras; D006321:Heart / Q000000981:diagnostic imaging*; D007527:Isoenzymes; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging*; D009206:Myocardium / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D010091:Oximes / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats
D003287:Contrast Media; D007527:Isoenzymes; D015609:Organotechnetium Compounds; D010091:Oximes; C105527:technetium Tc 99m 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime; D003402:Creatine Kinase