Cyclotron Production of High-Specific Activity 55Co and In Vivo Evaluation of the Stability of 55Co Metal-Chelate-Peptide Complexes.

This work describes the production of high-specific activity 55Co and the evaluation of the stability of 55Co-metal-chelate-peptide complexes in vivo. 55Co was produced via the 58Ni(p,α)55Co reaction and purified using anion exchange chromatography with an average recovery of 92% and an average specific activity of 1.96 GBq/µmol. 55Co-DO3A and 55Co-NO2A peptide complexes were radiolabeled at 3.7 MBq/µg and injected into HCT-116 tumor xenografted mice. Positron emission tomography (PET) and biodistribution studies were performed at 24 and 48 hours postinjection and compared to those of 55CoCl2. Both 55Co-metal-chelate complexes demonstrated good in vivo stability by reducing the radiotracers' uptake in the liver by sixfold at 24 hours with ~ 1% ID/g and at 48 hours with ~ 0.5% ID/g and reducing uptake in the heart by fourfold at 24 hours with ~ 0.7% ID/g and sevenfold at 48 hours with ~ 0.35% ID/g. These results support the use of 55Co as a promising new radiotracer for PET imaging of cancer and other diseases.

Specific activity measurement of 64Cu: a comparison of methods.

Effective specific activity of (64)Cu (amount of radioactivity per µmol metal) is important in order to determine purity of a particular (64)Cu lot and to assist in optimization of the purification process. Metal impurities can affect effective specific activity and therefore it is important to have a simple method that can measure trace amounts of metals. This work shows that ion chromatography (IC) yields similar results to ICP mass spectrometry for copper, nickel and iron contaminants in (64)Cu production solutions.

Measurement of myocardial fatty acid esterification using [1-11C]palmitate and PET: comparison with direct measurements of myocardial triglyceride synthesis.

BACKGROUND: The purpose of the present study was to assess the accuracy of rates of myocardial fatty acid esterification (MFAE) obtained using positron emission tomography (PET). METHODS AND RESULTS: Sixteen dogs were studied after an overnight fast (FAST), during a euglycemic hyperinsulinemic clamp (CLAMP), or during infusion of intralipid (IL) or IL plus dobutamine (IL/DOB). MFAE was quantified using [1-(11)C]palmitate and PET and compared to the rate of triglyceride (TG) synthesis measured using [1-(13)C]palmitate and tissue sampling. Plasma free fatty acid (FFA) concentration varied approximately 20-fold across groups, with this variation in FFA availability accompanied by a approximately 20-fold range in TG synthesis. MFAE varied approximately 12-fold across groups, and was significantly correlated with TG synthesis (R = 0.80, P < .001). MFAE, however, was 3- to 4-fold higher than TG synthesis in FAST, CLAMP, and IL, but only approximately 50% higher when cardiac work was increased in IL/DOB, suggesting that MFAE reflects, in part, the incorporation of label into amino acids via TCA cycle exchange reactions. CONCLUSIONS: Changes in MFAE parallel changes in TG synthesis, at least in the basal state. Although the data need to be interpreted cautiously, such measurements should be useful for quantifying acute changes in FFA storage by the heart in various pathophysiological states.

L-3-11C-lactate as a PET tracer of myocardial lactate metabolism: a feasibility study.

UNLABELLED: Lactate is a key myocardial energy source. Lactate metabolism is altered in a variety of conditions, such as exercise and diabetes mellitus. However, to our knowledge, noninvasive quantitative measurements of myocardial lactate metabolism have never been performed because of the lack of an adequate radiotracer. In this study we tested L-3-(11)C-lactate ((11)C-lactate) as such a tracer. METHODS: Twenty-three dogs were studied under a wide range of metabolic interventions. (11)C-Lactate and (13)C-lactate were injected as boluses and PET data were acquired for 1 h. Concomitant arterial and coronary sinus (ART/CS) blood samples were collected to identify (13)C-lactate metabolites and to measure fractional myocardial extraction/production of (11)C metabolite fractions ((11)C acidic: (11)CO(2) and (11)C-lactate; (11)C basic: (11)C-labeled amino acids; and (11)C neutral: (11)C-glucose). Lactate metabolism was quantified using 2 PET approaches: monoexponential clearance analysis (oxidation only) and kinetic modeling of PET (11)C-myocardial curves. RESULTS: Arterial (11)C acidic, neutral, and basic metabolites were identified as primarily (11)C-labeled lactate + pyruvate, glucose, and alanine, respectively. Despite a significant contribution of (11)C-glucose (23%-45%) and (11)C-alanine (<11%) to total arterial (11)C activity, both were minimally extracted(+)/produced(-) by the heart (1.7% +/- 1.0% and -0.12% +/- 0.84%, respectively). Whereas extraction of (11)C-lactate correlated nonlinearly with that of unlabeled lactate extraction (r = 0.86, P < 0.0001), (11)CO(2) production correlated linearly with extraction of unlabeled lactate (r = 0.89, P < 0.0001, slope = 1.20 +/- 0.13). In studies with physiologic free fatty acids (FFA) (415 +/- 216 nmol/mL), (11)C-lactate was highly extracted (32% +/- 12%) and oxidized (26% +/- 14%), and PET monoexponential clearance and kinetic modeling analyses resulted in accurate estimates of lactate oxidation and metabolism. In contrast, supraphysiologic levels of plasma FFA (4,111 +/- 1,709 nmol/mL) led to poor PET estimates of lactate metabolism due to negligible lactate oxidation (1% +/- 2%) and complete backdiffusion of unmetabolized (11)C-lactate into the vasculature (28% +/- 22%). CONCLUSION: Under conditions of net lactate extraction, L-3-(11)C-lactate faithfully traces myocardial metabolism of exogenous lactate. Furthermore, in physiologic substrate environments, noninvasive measurements of lactate metabolism are feasible with PET using myocardial clearance analysis (oxidation) or compartmental modeling. Thus, L-3-(11)C-lactate should prove quite useful in widening our understanding of the role that lactate oxidation plays in the heart and other tissues and organs.

PET measurements of myocardial glucose metabolism with 1-11C-glucose and kinetic modeling.

UNLABELLED: The aim of this study was to investigate whether compartmental modeling of 1-(11)C-glucose PET kinetics can be used for noninvasive measurements of myocardial glucose metabolism beyond its initial extraction. METHODS: 1-(11)C-Glucose and U-(13)C-glucose were injected simultaneously into 22 mongrel dogs under a wide range of metabolic states; this was followed by 1 h of PET data acquisition. Heart tissue samples were analyzed for (13)C-glycogen content (nmol/g). Arterial and coronary sinus blood samples (ART/CS) were analyzed for glucose (mumol/mL), (11)C-glucose, (11)CO(2), and (11)C-total acidic metabolites ((11)C-lactate [LA] + (11)CO(2)) (counts/min/mL) and were used to calculate myocardial fractions of (a) glucose and 1-(11)C-glucose extractions, EF(GLU) and EF((11)C-GLU); (b) (11)C-GLU and (11)C-LA oxidation, OF((11)C-GLU) and OF((11)C-LA); (c) (11)C-glycolsysis, GCF((11)C-GLU); and (d) (11)C-glycogen content, GNF((11)C-GLU). On the basis of these measurements, a compartmental model (M) that accounts for the contribution of exogenous (11)C-LA to myocardial (11)C activity was implemented to measure M-EF(GLU), M-GCF(GLU), M-OF(GLU), M-GNF(GLU), and the fraction of myocardial glucose stored as glycogen M-GNF(GLU)/M-EF(GLU)). RESULTS: ART/CS data showed the following: (a) A strong correlation was found between EF((11)C-GLU) and EF(GLU) (r = 0.92, P < 0.0001; slope = 0.95, P = not significantly different from 1). (b) In interventions with high glucose extraction and oxidation, the contribution of OF((11)C-GLU) to total oxidation was higher than that of OF((11)C-LA) (P < 0.01). In contrast, in interventions in which glucose uptake and oxidation were inhibited, OF((11)C-LA) was higher than OF((11)C-GLU) (P < 0.05). (c) A strong correlation was found between GNF((11)C-GLU)/EF(GLU) and direct measurements of fractional (13)C-glycogen content, (r = 0.96, P < 0.0001). Model-derived PET measurements of M-EF(GLU), M-GCF(GLU), and M-OF(GLU) strongly correlated with EF(GLU) (slope = 0.92, r = 0.95, P < 0.0001), GCF((11)C-GLU) (slope = 0.79, r = 0.97, P < 0.0001), and OF((11)C-GLU) (slope = 0.70, r = 0.96, P < 0.0001), respectively. M-GNF(GLU)/M-EF(GLU) strongly correlated with fractional (13)C-content (r = 0.92, P < 0.0001). CONCLUSION: Under nonischemic conditions, it is feasible to measure myocardial glucose metabolism noninvasively beyond its initial extraction with PET using 1-(11)C-glucose and a compartmental modeling approach that takes into account uptake and oxidation of secondarily labeled exogenous (11)C-lactate.

CO2-enhanced CT imaging for the detection of pulmonary emboli: feasibility study in a porcine model.

RATIONALE AND OBJECTIVES: The authors investigated the feasibility of using computed tomography (CT) with CO2 gas as a negative contrast agent for detecting pulmonary emboli in a porcine model. MATERIALS AND METHODS: Seven pigs with or without pulmonary emboli underwent thoracic imaging with multi-detector row spiral CT. To identify optimal injection and scanning protocols, the first four pigs were scanned repeatedly in the supine and prone positions with different scan delays (10, 15, and 20 seconds) and different volumes of CO2 (60, 120, 180, and 240 mL), which were hand infused (each infusion took 10-15 seconds). The last five pigs with emboli were scanned with iodinated contrast medium and then rescanned with 120 or 180 mL of CO2. The CO2 volumes and scan delays were qualitatively assessed. The supine and prone CT scans and the number and location of thrombi depicted in the CO2- and contrast material-enhanced CT scans were compared. RESULTS: Because the pulmonary artery in pigs is in the posterior anatomy, the prone position was more effective than the supine position with CO2 enhancement. An infusion of 120 mL of CO2 was sufficient to enhance the entire pulmonary artery, and scanning timed to coincide with the completion of infusion was the most effective. Both the CO2- and contrast-enhanced CT scans demonstrated all thrombi. Thrombi were more apparent on the CO2-enhanced CT scans than on the contrast-enhanced scans because of the high contrast interface between soft tissue and gas. However, two of the seven pigs with thrombi experienced abrupt cardiac arrest after CO2-enhanced scanning and could not be resuscitated. The cause of these events was not determined in the current study. CONCLUSION: The CT depiction of pulmonary emboli is feasible with CO2 gas as a negative contrast agent and may even be superior to that with iodinated contrast media. Further studies are required to evaluate the safety of this method and to develop an improved delivery of CO2 gas for this application.