Equivalence of arterial and venous blood for [11C]CO2-metabolite analysis following intravenous administration of 1-[11C]acetate and 1-[11C]palmitate

Abstract

Purpose: Sampling of arterial blood for metabolite correction is often required to define a true radiotracer input function in quantitative modeling of PET data. However, arterial puncture for blood sampling is often undesirable. To establish whether venous blood could substitute for arterial blood in metabolite analysis for quantitative PET studies with 1-[(11)C]acetate and 1-[(11)C]palmitate, we compared the results of [(11)C]CO2-metabolite analyses performed on simultaneously collected arterial and venous blood samples.

Methods: Paired arterial and venous blood samples were drawn from anesthetized pigs at 1, 3, 6, 8, 10, 15, 20, 25 and 30min after i.v. administration of 1-[(11)C]acetate and 1-[(11)C]palmitate. Blood radioactivity present as [(11)C]CO2 was determined employing a validated 10-min gas-purge method. Briefly, total blood (11)C radioactivity was counted in base-treated [(11)C]-blood samples, and non-[(11)C]CO2 radioactivity was counted after the [(11)C]-blood was acidified using 6N HCl and bubbled with air for 10min to quantitatively remove [(11)C]CO2.

Results: An excellent correlation was found between concurrent arterial and venous [(11)C]CO2 levels. For the [(11)C]acetate study, the regression equation derived to estimate the venous [(11)C]CO2 from the arterial values was: y=0.994x+0.004 (r(2)=0.97), and for the [(11)C]palmitate: y=0.964x-0.001 (r(2)=0.9). Over the 1-30min period, the fraction of total blood (11)C present as [(11)C]CO2 rose from 4% to 64% for acetate, and 0% to 24% for palmitate. The rate of [(11)C]CO2 appearance in venous blood appears similar for the pig model and humans following i.v. [(11)C]-acetate administration.

Conclusion: Venous blood [(11)C]CO2 values appear suitable as substitutes for arterial blood samples in [(11)C]CO2 metabolite analysis after administration of [(11)C]acetate or [(11)C]palmitate

Advances in knowledge and implications for patient care: Quantitative PET studies employing 1-[(11)C]acetate and 1-[(11)C]palmitate can employ venous blood samples for metabolite correction of an image-derived tracer arterial input function, thereby avoiding the risks of direct arterial blood sampling.

Fig. 1

Concordance of measured arterial and venous [¹¹C]CO₂ levels. For [¹¹C]acetate (A), the data shown represent a total of 34 paired swine arterial and venous blood samples collected at times: 1, 3, 6, 8,10, 15, 20, 25 and 30 minutes post- i.v injection (y = 0.994x + 0.004; r²= 0.97). At all time points from 1-30 minutes post-injection, venous and arterialblood concentrations of [¹¹C]CO₂ appear essentially identical.For [¹¹C]palmitate (B), the data shown represent 26 paired blood samples collected at 6, 8, 10, 15, 20, 25 and 30 minutes post-i.v injection (y = 0.964x - 0.011; r²=0.9). Data from one and three minutes post injection of [¹¹C]palmitate are omitted due to the absence of ¹¹CO₂ in blood.

Fig. 1

Concordance of measured arterial and venous [¹¹C]CO₂ levels. For [¹¹C]acetate (A), the data shown represent a total of 34 paired swine arterial and venous blood samples collected at times: 1, 3, 6, 8,10, 15, 20, 25 and 30 minutes post- i.v injection (y = 0.994x + 0.004; r²= 0.97). At all time points from 1-30 minutes post-injection, venous and arterialblood concentrations of [¹¹C]CO₂ appear essentially identical.For [¹¹C]palmitate (B), the data shown represent 26 paired blood samples collected at 6, 8, 10, 15, 20, 25 and 30 minutes post-i.v injection (y = 0.964x - 0.011; r²=0.9). Data from one and three minutes post injection of [¹¹C]palmitate are omitted due to the absence of ¹¹CO₂ in blood.

Fig. 2

Fractions of arterial and venous total blood radioactivity present as ¹¹CO₂ following i.v. administration of [¹¹C]acetate and [¹¹C]palmitate to miniaturepig (A; n =4), and human (B; n = 6).In pig, the percentage of ¹¹CO₂ rose from 4% to 64% for acetate, and 0% to 24% for palmitate, over a 30-minute period following the i.v administration of the indicated tracer. The rate of ¹¹CO₂ appearance in human blood following[¹¹C]acetate administration is very similar to the finding in the pig model. Values given are% ¹¹CO₂ in blood (mean±S.D.)[x : arterial blood; ● : venous blood].

Fig. 2

Fractions of arterial and venous total blood radioactivity present as ¹¹CO₂ following i.v. administration of [¹¹C]acetate and [¹¹C]palmitate to miniaturepig (A; n =4), and human (B; n = 6).In pig, the percentage of ¹¹CO₂ rose from 4% to 64% for acetate, and 0% to 24% for palmitate, over a 30-minute period following the i.v administration of the indicated tracer. The rate of ¹¹CO₂ appearance in human blood following[¹¹C]acetate administration is very similar to the finding in the pig model. Values given are% ¹¹CO₂ in blood (mean±S.D.)[x : arterial blood; ● : venous blood].

Fig. 3

While exhaled ¹¹CO₂ precludes arterial and venous blood from having absolutely identical concentrations of the [¹¹C]CO₂ metabolite of [¹¹C]acetate and [¹¹C]palmitate, the data from this study indicates that venous blood samples remain an excellent surrogate for quantifying the fraction of blood ¹¹C radioactivity present as [¹¹C]CO₂ after i.v. administration of these radiopharmaceuticals.

Fig. 3

While exhaled ¹¹CO₂ precludes arterial and venous blood from having absolutely identical concentrations of the [¹¹C]CO₂ metabolite of [¹¹C]acetate and [¹¹C]palmitate, the data from this study indicates that venous blood samples remain an excellent surrogate for quantifying the fraction of blood ¹¹C radioactivity present as [¹¹C]CO₂ after i.v. administration of these radiopharmaceuticals.

Fig. 4

Representative normalized decay-corrected arterial blood time-radioactivity curves obtained from a single pig by direct measurement of ¹¹C radioactivity in sampled arterial blood. The [¹¹C]-acetate (A) and [¹¹C]-palmitate (B) are both fairly cleared rapidly from blood, with the [¹¹C]CO₂ metabolite representing a significant fraction of the total radioactivity beyond a few minutes post-injection.