TY - JOUR
T1 - Effects of specific activity on meta-[131I]iodobenzylguanidine kinetics in isolated rat heart
AU - DeGrado, Timothy R.
AU - Zalutsky, Michael R.
AU - Coleman, R. Edward
AU - Vaidyanathan, Ganesan
N1 - Funding Information:
The authorst hankD . A&k for her technicaal ssistancein synthesigng NCA [‘3111MIBG. This work was supported in part by grants HL-54882 and CA-60066 from theN ational Instituteso f Health. We thank Smithl&ne-Beechamfo r prowisiono f SKF550.
PY - 1998/1
Y1 - 1998/1
N2 - The effects of specific activity of meta-[131I]iodobenzylguanidine (MIBG) were studied in uptake-2 blocked isolated perfused rat heart. [131I]MIBG was administered in the perfusate as an 8-min pulse, followed by an 80-min washout period. Kinetic analysis of the externally monitored time-activity curves gave estimates of uptake rate and multiexponential clearance. Uptake rate showed an MIBG concentration dependence that is sigmoidal, yielding Michaelis-Menten constants K(M) = 52 nM and V(max) = 0.23 nmol/min/g. Clearance rate was also dependent on loading MIBG concentrations; the primary effect of increasing loading concentration was an increase in the rate of the slowest clearance component, possibly reflecting nonspecific turnover. No effect of specific activity was observed on tissue uptake and retention of [131I]MIBG for loading concentrations of MIBG in the heart tissue under 0.5 nmol/g. Extrapolation of these results to human studies indicates that isotope-exchange-labeled [123I]MIBG has a specific activity sufficiently high to avoid mass effects on its heart retention.
AB - The effects of specific activity of meta-[131I]iodobenzylguanidine (MIBG) were studied in uptake-2 blocked isolated perfused rat heart. [131I]MIBG was administered in the perfusate as an 8-min pulse, followed by an 80-min washout period. Kinetic analysis of the externally monitored time-activity curves gave estimates of uptake rate and multiexponential clearance. Uptake rate showed an MIBG concentration dependence that is sigmoidal, yielding Michaelis-Menten constants K(M) = 52 nM and V(max) = 0.23 nmol/min/g. Clearance rate was also dependent on loading MIBG concentrations; the primary effect of increasing loading concentration was an increase in the rate of the slowest clearance component, possibly reflecting nonspecific turnover. No effect of specific activity was observed on tissue uptake and retention of [131I]MIBG for loading concentrations of MIBG in the heart tissue under 0.5 nmol/g. Extrapolation of these results to human studies indicates that isotope-exchange-labeled [123I]MIBG has a specific activity sufficiently high to avoid mass effects on its heart retention.
KW - Catecholamine uptake
KW - Meta-lodobenzylguanidine
KW - Perfused rat heart
KW - Sympathetic nervous system
KW - Uptake-1
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U2 - 10.1016/S0969-8051(97)00158-3
DO - 10.1016/S0969-8051(97)00158-3
M3 - Article
C2 - 9466363
AN - SCOPUS:0031986066
SN - 0969-8051
VL - 25
SP - 59
EP - 64
JO - Nuclear Medicine and Biology
JF - Nuclear Medicine and Biology
IS - 1
ER -