Relationship between histologic type of primary lung cancer and carbon-11-L-methionine uptake with positron emission tomography

L-[Methyl-11C]-methionine [( 11C]methionine) has proved to be one of the useful amino acids for the diagnosis of human cancer. We examined whether there was any correlation between [11C]methionine uptake and histologic type of primary lung cancer. Sixteen patients with nine squamous cell carcinoma, five large cell carcinoma, one small cell carcinoma, and one adenocarcinoma were studied using positron emission tomography (PET). All patients had high accumulation of [11C]methionine in lung tumors. We evaluated [11C]methionine uptake into the tumor by a semiquantitative value, DUR (Differential Uptake Ratio). There was significant difference (p less than 0.01, Mann-Whitney test) of [11C]methionine uptake between large cell carcinoma (3.98 +/- 0.27) and squamous cell carcinoma (2.92 +/- 0.30). The result suggested that there was correlation between [11C]methionine accumulation and the histologic type of lung cancer. This indicates a new potential applicability of [11C]methionine PET for the study of lung cancer.     

Innovative approach in the diagnosis of gliomatosis cerebri using carbon-11-L-methionine positron emission tomography

A case of gliomatosis cerebri was studied with positron emission tomography (PET). Carbon-11-L-methionine (11C-Met) accumulated in the diffusely infiltrative tumorous area more widely and accurately than the lesion detected by conventional x-ray computerized tomography (CT) or magnetic resonance (MR) imaging. Autopsy findings three months after the time of the PET study showed good anatomical correspondence between the extent of densely aggregated tumor cells and the region with high uptake of 11C-Met. PET may offer an innovative approach in the delineation of gliomatosis cerebri, which has not been clearly recognized by CT or MR.     

Experience with carbon-11 choline positron emission tomography in prostate carcinoma

We investigated the potential of carbon-11 choline positron emission tomography (PET) for the detection of lymph node and bone metastases in prostate cancer. A total of 23 patients were studied (known metastases: 8; suspicion of metastases: 3; primary staging: 12). Whole-body PET imaging was performed 5 min after injection of the tracer and completed within 1 h. Focally increased tracer uptake in bone or abdominal lymph node regions was interpreted as representing tumour involvement. All known bone and lymph node metastases could be recognized by [¹¹C]choline PET. One out of ten negative scans for primary staging was false-negative (lymph node <1 cm) and one out of two positive scans was false-positive with regard to lymph node involvement (focal bowel activity). It is concluded that [¹¹C]choline PET is a promising new tool for the primary staging of prostate cancer, with lymph node and bone metastases demonstrating high tracer uptake. Therapeutic management could be influenced by these results in that the technique may permit avoidance of surgical lymph node exploration.     

Experience with carbon-11 choline positron emission tomography in prostate carcinoma

We investigated the potential of carbon-11 choline positron emission tomography (PET) for the detection of lymph node and bone metastases in prostate cancer. A total of 23 patients were studied (known metastases: 8; suspicion of metastases: 3; primary staging: 12). Whole-body PET imaging was performed 5 min after injection of the tracer and completed within 1 h. Focally increased tracer uptake in bone or abdominal lymph node regions was interpreted as representing tumour involvement. All known bone and lymph node metastases could be recognized by [11C]choline PET. One out of ten negative scans for primary staging was false-negative (lymph node <1 cm) and one out of two positive scans was false-positive with regard to lymph node involvement (focal bowel activity). It is concluded that [11C]choline PET is a promising new tool for the primary staging of prostate cancer, with lymph node and bone metastases demonstrating high tracer uptake. Therapeutic management could be influenced by these results in that the technique may permit avoidance of surgical lymph node exploration.     

In vivo measurement of carbon-11 thymidine uptake in non-Hodgkin's lymphoma using positron emission tomography

Carbon-11 thymidine (TdR) uptake using positron emission tomography (PET) has been measured in ten patients with non-Hodgkin's lymphoma (NHL). The rate of TdR uptake (mean +/- s.d.) was of 0.009 +/- 0.006 mumol.100 cc-1.min-1 in low-grade NHL. This rate was 0.063 +/- 0.049 mumol.100 cc-1.min-1 in intermediate-grade NHL and 0.159 mumol.100 cc-1.min-1 in a patient with high-grade NHL. Lymphoma radioactivity reached a plateau at 0.42 +/- 0.22%. 100 cc-1 of the injected dose from 10 min after injection. The highest 11C uptakes were observed in the kidneys and in the liver (3.30 +/- 1.30 and 2.10 +/- 0.05%. 100 cc-1 of the injected dose, respectively). The lymphoma-to-muscle ratio was of 11.8 +/- 1.7, whereas the lymphoma-to-intestine ratio was of 1.5 +/- 0.7. Accordingly, the measurement of [11C]TdR uptake in the abdomen may need other imaging methods for adequate interpretation. The results suggest that [11C]TdR uptake using PET might be a method for noninvasively measuring cell proliferation in vivo.     

Absolute quantitation of iodine-123 epidepride kinetics using single-photon emission tomography: comparison with carbon-11 epidepride and positron emission tomography

Epidepride labelled with iodine-123 is a suitable probe for the in vivo imaging of striatal and extrastriatal dopamine D₂ receptors using single-photon emission tomography (SPET). Recently, this molecule has also been labelled with carbon-11. The goal of this work was to develop a method allowing the in vivo quantification of radioactivity uptake in baboon brain using SPET and to validate it using positron emission tomography (PET). SPET studies were performed in Papio anubis baboons using ¹²³I-epidepride. Emission and transmission measurements were acquired on a dual-headed system with variable head angulation and low-energy ultra-high resolution (LEUHR) collimation. The imaging protocol consisted of one transmission measurement (24 min, heads at 90°), obtained with two sliding line sources of gadolinium-153 prior to injection of 0.21–0.46 GBq of ¹²³I-epidepride, and 12 emission measurements starting 5 min post injection. For scatter correction (SC) we used a dual-window method adapted to ¹²³I. Collimator blurring correction (CBC) was done by deconvolution in Fourier space and attenuation correction (AT) was applied on a preliminary (CBC) filtered back-projection reconstruction using 12 iterations of a preconditioned, regularized minimal residual algorithm. For each reconstruction, a calibration factor was derived from a uniform cylinder filled with a ¹²³I solution of a known radioactivity concentration. Calibration and baboon images were systematically built with the same reconstruction parameters. Uncorrected (UNC) and (AT), (SC+AT) and (SC+CBC+AT) corrected images were compared. PET acquisitions using 0.11–0.44 GBq of ¹¹C-epidepride were performed on the same baboons and used as a reference. The radioactive concentrations expressed in percent of the injected dose per 100 ml (%ID/100 ml) obtained after (SC+CBC+AT) in SPET are in good agreement with those obtained with PET and ¹¹C-epidepride. A method for the in vivo absolute quantitation of ¹²³I-epidepride uptake using SPET has been developed which can be directly applied to other ¹²³I-labelled molecules used in the study of the dopamine system. Further work will consist in using PET to model the radioligand-receptor interactions and to derive a simplified model applicable in SPET.     

Absolute quantitation of iodine-123 epidepride kinetics using single-photon emission tomography: comparison with carbon-11 epidepride and positron emission tomography

Epidepride labelled with iodine-123 is a suitable probe for the in vivo imaging of striatal and extrastriatal dopamine D2 receptors using single-photon emission tomography (SPET). Recently, this molecule has also been labelled with carbon-11. The goal of this work was to develop a method allowing the in vivo quantification of radioactivity uptake in baboon brain using SPET and to validate it using positron emission tomography (PET). SPET studies were performed in Papio anubis baboons using 123I-epidepride. Emission and transmission measurements were acquired on a dual-headed system with variable head angulation and low-energy ultra-high resolution (LEUHR) collimation. The imaging protocol consisted of one transmission measurement (24 min, heads at 90 degrees), obtained with two sliding line sources of gadolinium-153 prior to injection of 0.21-0.46 GBq of 123I-epidepride, and 12 emission measurements starting 5 min post injection. For scatter correction (SC) we used a dual-window method adapted to 123I. Collimator blurring correction (CBC) was done by deconvolution in Fourier space and attenuation correction (AT) was applied on a preliminary (CBC) filtered back-projection reconstruction using 12 iterations of a preconditioned, regularized minimal residual algorithm. For each reconstruction, a calibration factor was derived from a uniform cylinder filled with a 123I solution of a known radioactivity concentration. Calibration and baboon images were systematically built with the same reconstruction parameters. Uncorrected (UNC) and (AT), (SC + AT) and (SC + CBC + AT) corrected images were compared. PET acquisitions using 0.11-0.44 GBq of 11C-epidepride were performed on the same baboons and used as a reference. The radioactive concentrations expressed in percent of the injected dose per 100 ml (% ID/100 ml) obtained after (SC + CBC + AT) in SPET are in good agreement with those obtained with PET and 11C-epidepride. A method for the in vivo absolute quantitation of 123I-epidepride uptake using SPET has been developed which can be directly applied to other 123I-labelled molecules used in the study of the dopamine system. Further work will consist in using PET to model the radioligand-receptor interactions and to derive a simplified model applicable in SPET.     

Glucose transport and utilization in the human brain: model using carbon-11 methylglucose and positron emission tomography

3-0-[11C]-Methyl-D-glucose (CMG) is specifically suited for measuring carrier facilitated glucose (G) transport; it enters the free G pool in tissue from where it is not utilized for metabolism in contrast to G, but is transported back into circulation. The ratio of carrier affinity for G and CMG was reported to be 1.11. By simultaneously measuring CMG concentration in plasma and in cerebral cortex in vivo with positron tomography at 1-min intervals for 40 min, two time-activity curves are obtained, as reported previously, which together with the G concentration in plasma yield the in vivo rate constants of G transport across the blood-brain barrier and the rate of G inflow; a repeat measurement at a different G concentration in plasma gives the in vivo Michaelis-Menten constant KM and the maximal rate of transport VMAX. The present paper summarizes and extends this approach to analyzing the free G pool in tissue, the rate of G return to circulation, and the rate of G exit into metabolism with its corresponding rate constants. The data from six volunteers agreed with results reported for the individual biochemical parameters in primate brains.     

Synthesis and positron emission tomography studies of carbon-11-labeled imatinib (Gleevec)

INTRODUCTION: Imatinib mesylate (Gleevec) is a well known drug for treating chronic myeloid leukemia and gastrointestinal stromal tumors. Its active ingredient, imatinib ([4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridyl)-2-pyrimidinyl]amino]phenyl]benzamide), blocks the activity of several tyrosine kinases. Here we labeled imatinib with carbon-11 as a tool for determining the drug distribution and pharmacokinetics of imatinib, and we carried out positron emission tomography (PET) studies in baboons. METHODS: [N-(11)C-methyl]imatinib was synthesized from [(11)C]methyl iodide and norimatinib was synthesized by the demethylation of imatinib (isolated from Gleevec tablets) according to a patent procedure [Collins JM, Klecker RW Jr, Anderson LW. Imaging of drug accumulation as a guide to antitumor therapy. US Patent 20030198594A1, 2003]. Norimatinib was also synthesized from the corresponding amine and acid. PET studies were carried out in three baboons to measure pharmacokinetics in the brain and peripheral organs and to determine the effect of a therapeutic dose of imatinib. Log D and plasma protein binding were also measured. RESULTS: [N-(11)C-methyl]imatinib uptake in the brain is negligible (consistent with P-glycoprotein-mediated efflux); it peaks and clears rapidly from the heart, lungs and spleen. Peak uptake and clearance occur more slowly in the liver and kidneys, followed by accumulation in the gallbladder and urinary bladder. Pretreatment with imatinib did not change uptake in the heart, lungs, kidneys and spleen, and increased uptake in the liver and gallbladder. CONCLUSIONS: [N-(11)C-methyl]imatinib has potential for assessing the regional distribution and kinetics of imatinib in the human body to determine whether the drug targets tumors and to identify other organs to which the drug or its labeled metabolites distribute. Paired with tracers such as 2'deoxy-2'-[(18)F]fluoro-D-glucose ((18)FDG) and 3'deoxy-3'-[(18)F]fluorothymidine ((18)FLT), [N-(11)C-methyl]imatinib may be a useful radiotracer for planning chemotherapy, for monitoring response to treatment and for assessing the role of drug pharmacokinetics in drug resistance.     

Assessment of myocardial oxidative metabolic reserve with positron emission tomography and carbon-11 acetate

We have previously demonstrated that positron emission tomography (PET) with [11C]acetate allows noninvasive regional quantification of myocardial oxidative metabolism. To assess the metabolic response of normal myocardium to increased work (oxidative metabolic reserve), clearance of myocardial 11C activity after administration of [11C]acetate i.v. was measured with PET in seven normal subjects at rest and during dobutamine infusion. At rest, clearance of 11C was monoexponential and homogeneous. The rate constant of the first phase of 11C clearance, k1, averaged 0.054 +/- 0.014 min-1 at a rate-pressure produce (RPP) of 7329 +/- 1445 mmHg X bpm. During dobutamine infusion, RPP increased by an average of 141% to 17,493 +/- 3582 mm Hg Z bpm. Clearance of 11C became biexponential and remained homogeneous. k1 averaged 0.198 +/- 0.043 min-1 with a mean coefficient of variation of 16%.. k1 and RPP correlated closely (r = 0.91; p less than 0.001), and the slope of the k1/RPP relation remained consistent in all subjects (1.48 +/- 0.42). These findings suggest that PET with [11C]acetate and dobutamine stress may provide a promising approach for evaluation of regional myocardial oxidative metabolic reserve in patients with cardiac diseases of diverse etiologies and for assessment of the efficacy of interventions designed to enhance the recovery of metabolically comprised myocardium.     

Non-invasive estimation of myocardial efficiency using positron emission tomography and carbon-11 acetate--comparison between the normal and failing human heart

The clearance kinetics of carbon-11 acetate, assessed by positron emission tomography (PET), can be combined with measurements of ventricular function for non-invasive estimation of myocardial oxygen consumption and efficiency. In the present study, this approach was applied to gain further insights into alterations in the failing heart by comparison with results obtained in normals. We studied ten patients with idiopathic dilated cardiomyopathy (DCM) and 11 healthy normals by dynamic PET with 11C-acetate and either tomographic radionuclide ventriculography or cine magnetic resonance imaging. A "stroke work index" (SWI) was calculated by: SWI = systolic blood pressure x stroke volume/body surface area. To estimate myocardial efficiency, a "work-metabolic index" (WMI) was then obtained as follows: WMI = SWI x heart rate/k(mono), where k(mono) is the washout constant for 11C-acetate derived from monoexponential fitting. In DCM patients, left ventricular ejection fraction was 19%+/-10% and end-diastolic volume was 92+/-28 ml/m2 (vs 64%+/-7% and 55+/-8 ml/m2 in normals, P<0.001). Myocardial oxidative metabolism, reflected by k(mono), was significantly lower compared with that in normals (0.040+/-0.011/min vs 0.060+/-0.015/min; P<0.003). The SWI (1674+/-761 vs 4736+/-895 mmHg x ml/m2; P<0.001) and the WMI as an estimate of efficiency (2.98+/-1.30 vs 6.20+/-2.25 x 10(6) mmHg x ml/m2; P<0.001) were lower in DCM patients, too. Overall, the WMI correlated positively with ejection parameters (r=0.73, P<0.001 for ejection fraction; r=0.93, P<0.001 for stroke volume), and inversely with systemic vascular resistance (r=-0.77; P<0.001). There was a weak positive correlation between WMI and end-diastolic volume in normals (r=0.45; P=0.17), while in DCM patients, a non-significant negative correlation coefficient (r=-0.21; P=0.57) was obtained. In conclusion non-invasive estimates of oxygen consumption and efficiency in the failing heart were reduced compared with those in normals. Estimates of efficiency increased with increasing contractile performance, and decreased with increasing ventricular afterload. In contrast to normals, the failing heart was not able to respond with an increase in efficiency to increasing ventricular volume. The present data support the usefulness of the WMI for non-invasive characterization of cardiac efficiency and may serve as a background for improved evaluation of medical therapy for heart failure.     

The role of positron emission tomography using carbon-11 and fluorine-18 choline in tumors other than prostate cancer: a systematic review

To systematically review published data on the role of positron emission tomography (PET) or PET/computed tomography (PET/CT) using either Carbon-11 ((11)C) or Fluorine-18 ((18)F) choline tracer in tumors other than prostatic cancer. A comprehensive literature search of studies published in PubMed/MEDLINE and Embase databases through January 2012 and regarding (11)C-choline or (18)F-choline PET or PET/CT in patients with tumors other than prostatic cancer was carried out. Fifty-two studies comprising 1800 patients were included and discussed. Brain tumors were evaluated in 15 articles, head and neck tumors in 6, thoracic tumors (including lung and mediastinal neoplasms) in 14, liver tumors (including hepatocellular carcinoma) in 5, gynecologic malignancies (including breast tumors) in 5, bladder and upper urinary tract tumors in 5, and musculoskeletal tumors in 7. Radiolabeled choline PET or PET/CT is useful to differentiate high-grade from low-grade gliomas and malignant from benign brain lesions, to early detect brain tumor recurrences and to guide the stereotactic biopsy sampling. The diagnostic accuracy of radiolabeled choline PET is superior compared to Fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET in this setting. Radiolabeled choline PET or PET/CT seems to be accurate in differential diagnosis between malignant and benign thoracic lesions and in staging lung tumors; nevertheless, a superiority of radiolabeled choline compared to (18)F-FDG has not been demonstrated in this setting, except for the detection of brain metastases. Few but significant studies on radiolabeled choline PET and PET/CT in patients with hepatocellular carcinoma (HCC) and musculoskeletal tumors are reported in the literature. The combination of radiolabeled choline and (18)F-FDG PET increases the detection rate of HCC. The diagnostic accuracy of radiolabeled choline PET or PET/CT seems to be superior compared to (18)F-FDG PET or PET/CT and conventional imaging methods in patients with bone and soft tissue tumors. Limited experience exists about the role of radiolabeled choline PET and PET/CT in patients with head and neck tumors, bladder cancer and gynecologic malignancies including breast cancer.     

18F-fluorodeoxyglucose positron emission tomography in small-cell lung cancer

Positron emission tomography (PET) imaging is not used routinely in small-cell lung cancer (SCLC) but has been proven useful in non-small-cell lung cancer. The performance of (18)F-fluorodeoxyglucose (FDG)-PET in patients with SCLC was evaluated in this study. Fifteen patients with proven SCLC were evaluated (8 men and 7 women; mean age, 68 years; range, 50-81 years). Among the 15 patients with SCLC, 3 were newly diagnosed and 12 had received chemotherapy or radiation therapy before PET. Five patients underwent surgery (3 newly diagnosed and 2 after therapy) after PET scan, and 14 received chemotherapy, radiation therapy, or both. The patient who was not treated with chemotherapy or radiation therapy underwent surgery only. All patients had computed tomographic (CT) scans before PET and had clinical follow-up for at least 2 months after PET. The patients received 3.4 to 4.15 mCi of (18)F-FDG intravenously after fasting for at least 4 hours. Whole-body PET scans were acquired approximately 50 min after injection by using an ADAC Laboratories C-PET plus scanner. Among the 12 patients treated before PET, 2 were found with solitary pulmonary nodules positive on PET. Subsequent surgical resection and pathology showed 1 true positive and 1 false positive (postradiation pneumonitis). Six of these 12 patients had extrapulmonary metastases or large intense hilar or pulmonary uptake on PET, or both. Four of these 12 had no evidence of abnormal FDG uptake and were considered true negatives. The 3 patients with newly diagnosed SCLC were all true positives on PET, confirmed by surgery. One false negative on CT scan was attributed to postradiation fibrosis. These preliminary data suggest that whole-body FDG-PET can provide the basis for determining which treatment modality would be the most appropriate during the early stages of SCLC, when surgery is still an option, and it is a useful tool to assess the effect of treatment in patients with this disease. A more accurate assessment of SCLC will be possible if FDG-PET scan is combined with CT during the early evaluation of these patients.     

Localization of parathyroid adenomas using 11C-methionine positron emission tomography

BACKGROUND AND AIM: In symptomatic hyperparathyroidism, pre-surgical localization of the suspected site of adenoma is desirable. All widely available techniques may have difficulty in localizing the site. The aim of this study was to determine whether 11C-methionine positron emission tomography (PET) could accurately localize parathyroid adenomas in patients in whom conventional imaging had failed. PATIENTS AND METHODS: Fifty-one patients presenting with hyperparathyroidism, and in whom other imaging techniques had failed to definitely identify the site of adenoma, were reviewed retrospectively after 11C-methionine PET scanning. Patients were followed up by surgical histology, or clinically if surgery was not performed. RESULTS: 11C-Methionine PET scanning was found to have a sensitivity of 83%, a specificity of 100% and an accuracy of 88% in successfully locating parathyroid adenomas. Most false negatives were due to adenomas in the lower mediastinum that was outside the area of scanning. CONCLUSIONS: 11C-Methionine PET is a reliable and highly accurate technique for localizing parathyroid adenomas in patients in whom conventional imaging techniques have failed. It is necessary to image to the level of the lower mediastinum.     

Threshold modification for tumour imaging in non-small-cell lung cancer using positron emission tomography

AIM: Positron emission tomography (PET) has been used increasingly in the staging and radiotherapy treatment planning of non-small-cell lung cancer (NSCLC). This study investigates the factors that affect the resultant size of a given image on PET. METHODS: PET was used to assess the geometric characteristics of a series of radioisotope-filled, stationary spheres of known volume, surrounded by positron-emitting radioactive tracer of variable activity. The resultant PET-derived spherical volumes were then referenced to the known spherical volumes in order to illustrate quantitatively the potential influence of image threshold, tumour size and background concentration. This influence was further illustrated by clinical examples. RESULTS: Considering the diameter of the spheres used in this study (10-48 mm), higher image thresholds were required for accurate rendering of the smallest spherical volumes. This inverse relationship was most consistently illustrated at the lowest background intensity ratios. CONCLUSION: PET-derived volumes of NSCLC must be interpreted with caution. The data presented in this study may be used to guide the selection of appropriate image thresholds for potential clinical application.     

Lung tumor imaging by positron emission tomography using C-11 L-methionine

This paper described the first clinical study of lung tumor scanning by positron emission tomography (PET) using C-11-labeled L-methionine (11C-L-Met). Tumor images were clearly visualized by high contrast in eight lung cancer patients and also in a patient with a silicotic nodule. Quantitative evaluations of methionine uptake in tumor tissue and normal tissue by comparing differential uptake ratios suggested that the extent to which 11C-L-Met accumulates in a tumor is closely correlated to the tumor's viability such as benign or malignant, viable or necrotic. 11C-L-Met is considered to be an effective tumor marker for PET diagnosis which represents increased amino acid metabolism of tumors in the mediastinum and lung.     

Regional myocardial oxygen consumption estimated by carbon-11 acetate and positron emission tomography before and after repetitive ischemia

BACKGROUND: Preserved myocardial oxygen consumption estimated by carbon 11-acetate and positron emission tomography (PET) in myocardial regions with chronic but reversibly depressed contractile function in patients with ischemic heart disease have been suggested to be caused by repeated short episodes of acute myocardial ischemia. To evaluate this hypothesis myocardial 11C-acetate PET imaging was performed before and after acute repetitive myocardial ischemia. METHODS AND RESULTS: In open chest dogs (n = 8), the left anterior descending coronary artery was occluded 4 times for 5 minutes alternating with 5 minutes of reperfusion. Before and after repetitive coronary occlusions, oxygen 15 water/oxygen 15 carbon monoxide (blood flow), and 11C-acetate (oxygen consumption) PET imaging were performed. Left ventricular regional systolic wall thickening was measured with sonomicrometry. Forty-five minutes after the ischemic episodes, systolic ventricular wall thickening was decreased by 90%, whereas myocardial blood flow was reduced by 21% compared with baseline values (P < .05). Ninety minutes after the ischemic episodes, estimated oxygen consumption was unaltered compared with the baseline level despite a sustained 70% decrease in the regional contractile function (P < .05). CONCLUSIONS: Oxygen consumption estimated by 11C-acetate PET imaging is preserved after repeated episodes of acute myocardial ischemia despite a severe impairment of contractile function.     

Noninvasive assessment of regional cardiac adenosine using positron emission tomography.

One of the early metabolic changes associated with myocardial ischemia is the breakdown of adenine nucleotides resulting in the enhanced production of adenosine. In order to image regional cardiac adenosine by positron emission tomography (PET) the enzymatic conversion of adenosine into [11C]-S-adenosylhomocysteine ([11C]SAH) was used in the presence of 11C-labeled homocysteine thiolactone (adenosine + [11C] - homocysteine-->[11C] - SAH + H2O). Following production of an experimental coronary constriction in anesthetized dogs carrier added 1-[11C]-D,L-homocysteine thiolactone (5-27 mCi, 30 mg/kg) was infused over 1 min. This intervention, while hemodynamically ineffective, increased the plasma homocysteine concentration from 2.5 to 306 microM, which thereafter declined with a T1/2 of 28 min to 97 microM after 60 min. During the first minutes following infusion of [11C] homocysteine, the radioactivity concentration in the blood pool, the nonischemic and the ischemic myocardium were similar. Between 20 and 60 min, however, the regional radioactivity concentration was highest in the perfusion area of the stenosed vessel: 6.6% compared to 5.2 and 5.2% of the injected dose per 1 I tissue. The elevated radioactivity concentration was strictly confined to the perfusion area of the occluded artery. Using [35S]-L-homocysteine (20 microCi; 30 mg/kg) chromatographic separation of SAH in tissue extracts confirmed that the radioactivity accumulation was due to trapping of adenosine in the cellular SAH-pool. These experiments provide first evidence that 1-[11C]homocysteine thiolactone can be successfully used to assess regional adenosine formation in the heart with PET via measurement of [11C] SAH accumulation.     

An improved synthesis of carbon-11 labeled acetoacetic acid and an evaluation of its potential for the investigation of cerebral pathology by positron emission tomography

1-¹¹C-acetoacetic acid was synthesized by carboxylation of the acetone carbanion. Purification was carried out using HPLC. The product was obtained with a radiochemical yield of up to 58%, corrected for decay, in a total preparation time of 30 min. The distribution of 1-¹¹C-acetoacetic acid after injection into adult Wistar rats and cats was investigated by PET. When the tracer was injected into cats, 3 weeks after inflicting a unilateral freezing lesion upon the brain, accumulation of 1-¹¹C-acetoacetic acid in the ipsilateral brain hemisphere was observed.