Heart Uptake Research Articles

Characterization of cartilaginous tumors with201Tl scintigraphy

Histological diagnosis and grading of cartilaginous tumors are closely correlated with patient prognosis; consequently, they are essential elements. We attempted to clarify the characteristics of 201Tl uptake in various histological types of cartilaginous tumors and to assess its clinical value. Twenty-two cases with histologically proven cartilaginous tumors (3 enchondromas, 15 conventional chondrosarcomas (grade I = 9, II = 5, III = 1), 3 mesenchymal chondrosarcomas, and 1 de-differentiated chondrosarcoma) were examined retrospectively. Planar 201Tl images were recorded 15 min following intravenous injection of 201Tl (111 MBq). 201Tl uptake in the tumor was evaluated visually employing a five-grade scoring system: 0 = no appreciable uptake, 1 = faint uptake above the background level, 2 = moderate uptake, 3 = intense uptake but lower than heart uptake and 4 = uptake higher than heart uptake. 201Tl uptake scores were 0 in 3 of 3 enchondromas, 9 of 9 grade I, and 4 of 5 grade II conventional chondrosarcomas. 201Tl uptake scores were 1 among 1 of 5 grades II and a grade III conventional chondrosarcoma. Mesenchymal chondrosarcoma and de-differentiated chondrosarcoma displayed 201Tl uptake scores of 2 or 3. Absence of elevated 201Tl uptake in cartilaginous tumors was indicative of enchondroma or low-grade conventional chondrosarcoma. However, in instances in which 201Tl uptake is obvious, high-grade chondrosarcoma or variant types should be considered.

Adrenergic stimulation of Rb+ uptake in pig hearts in vivo assessed by 87Rb MRS

It was previously shown that the adrenergic agonist dobutamine stimulates Rb(+) uptake in isolated pig hearts. In the present work we examined whether dobutamine can increase Rb(+) uptake rate in vivo. Open-chest domestic pigs (N = 14) were used under general anesthesia. The surface coil was placed against the anterior left ventricular wall to obtain (87)Rb spectra using a spectrometer interfaced with the 7T, 30-cm horizontal bore magnet. RbCl was infused at the rate of 1.35 +/- 0.14 mmol/kg/hr without or with dobutamine (0.6 mg/kg/hr) over a 60-min period, and then the infusions were terminated. The rate constant (k x 10(3), from 13 +/- 2.4 to 36 +/- 12 min(-1)) and Rb(+) influx rate (from 2.5% to 4.8%/min) were increased by dobutamine despite lower plasma [Rb(+)] (0.59 +/- 0.16 vs. 0.84 +/- 0.24 mM in control), while the tissue/plasma Rb ratios were identical (38 +/- 9). Heart rate (HR) and systolic blood pressure (SBP) were increased from 106 +/- 9 to 161 +/- 15 bpm (+52%) and from 78 +/- 7 to 93 +/- 11 mmHg (+19%), respectively. The stimulation of Rb(+) uptake by dobutamine is consistent with the activation of Na(+)/K(+) ATPase previously observed in isolated hearts. However, the 50% increase in HR and the double coronary flow caused by the SBP increase and vasodilatation may also contribute to this effect.

99mTc carbonyl t-butyl isonitrile: A potential new agent for myocardial perfusion imaging

The recent development of mixed ligand complexes using a 99mTc tricarbonyl synthon has prompted us to revisit the first generation product, 99mTc-t-butyl isonitrile (TBI), for possible myocardial imaging after modification of the 99mTc core to a mixed ligand core of carbonyl and t-butyl isonitrile. The easy availability of TBI from commercial sources and the recent promising development of a 'kit' procedure to prepare the 99mTc tricarbonyl aqua synthon/precursor [99mTc(H2O)3(CO)3]+ were other factors that triggered this work. The carbonyl precursor (37-370 MBq/0.5 ml) was synthesized and reacted with TBI (3 mg.ml-1) at room temperature and at pH 8 for 1 h. [99mTc(CO)3(TBI)3]+ was characterized by C18 reverse phase HPLC in gradient mode with water and acetonitrile as solvent. Biodistribution studies were carried out in normal mice and planar images were acquired in rabbit at 5 min, 30 min, 1 h, 2 h and 4 h post-injection to assess heart uptake and soft tissue retention. [99mTc(CO)3(TBI)3]+was formed as a single species in >95% yield and was found to be stable. Biodistribution studies in mice revealed 2.3 (+/-0.2)% uptake in heart at 5 min p.i. with heart/liver, heart/lung and heart/blood ratios of 1.5, 2.0 and 30, respectively. Imaging studies in rabbits showed high uptake in myocardium, with negligible activity in blood and lungs, at 5 min p.i. that washed out of the heart after 4 h. [99mTc(CO)3(TBI)3]+ could be prepared in >95% yields. The complex showed high myocardial uptake with desirable rate of washout from heart in rabbits. [99mTc(CO)3(TBI)3]+ has potential to extend to larger animal studies and later for clinical evaluation as a myocardial imaging agent.

Lipomatous Hypertrophy of the Interatrial Septum: Increased Uptake on FDG PET

The objective of our study was to evaluate FDG uptake in patients with cardiac lipomatous hypertrophy of the interatrial septum (LHIS). Increased FDG uptake occurs in LHIS, a benign fatty infiltration of the interatrial septum. Increased uptake in the right heart on FDG PET warrants correlation with additional imaging to assess for LHIS and avoid false interpretation of malignancy.

Imaging DNA synthesis with [18F]FMAU and positron emission tomography in patients with cancer

FMAU (1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)thymine) is a thymidine analog that can be phosphorylated by thymidine kinase and incorporated into DNA. This first-in-human study of [18F]FMAU was conducted as a pilot in patients to determine its biodistribution and suitability for imaging DNA synthesis in tumors using positron emission tomography (PET). Fourteen patients with diverse cancers (brain, prostate, colorectal, lung, and breast) were imaged with [18F]FMAU. We obtained dynamic PET images for 60 min and a whole-body image. Blood and urine samples were analyzed by high-performance liquid chromatography to measure metabolites and clearance. Active tumors in the breast, brain, lung and prostate were clearly visualized with standardized uptake values (SUVs) of 2.19, 1.28, 2.21, and 2.27-4.42, respectively. Unlike with other tracers of proliferation, low uptake of [18F]FMAU was seen in the normal bone marrow (SUV(mean) 0.7), allowing visualization of metastatic prostate cancer (SUV 3.07). Low background was also observed in the brain, pelvis, and thorax, aside from heart uptake (SUV 3.36-8.78). In the abdomen, increased physiological uptake was seen in the liver (SUV 10.07-20.88) and kidneys (SUV 7.18-15.66) due to metabolism and/or excretion, but the urinary bladder was barely visible (SUV(mean) 2.03). On average, 95% of the activity in the blood was cleared within 10 min post injection and an average of 70% of the activity in the urine was intact FMAU at 60 min post injection. Tumors in the brain, prostate, thorax, and bone can be clearly visualized with FMAU. In the upper abdomen, visualization is limited by the physiological uptake by the liver and kidneys.

Heart and Soft-Tissue Uptake of Tc-99m MDP in a Hemodialysis Patient

Metastatic calcification related to renal failure has been well described. There is uptake of bone-scanning agents at extraskeletal sites in metastatic calcification. A 34-year-old man with end-stage renal failure was treated with hemodialysis. He noticed a painful lump over his right shoulder. Anterior and posterior whole-body bone scintigraphy images revealed markedly increased uptake in the heart, right shoulder, and medial part of the left shoulder. A biopsy of the right shoulder area showed metastatic calcium deposition.

In Vivo Imaging of Cardiovascular Endothelin Receptors Using the Novel Radiolabelled Antagonist [18F]-SB209670 and Positron Emission Tomography (microPET)

The aim of this study was to develop an F-labelled analogue of SB209670 with subnanomolar affinity for the endothelin receptor and to test whether it would have the required pharmacokinetic properties to permit binding and imaging of endothelin receptors in rat heart in vivo using small animal positron emission tomography (PET) imaging. [18F]-SB209670 could be produced in a total radiochemical yield of 14.9 +/- 3.8% in 162 +/- 7 minutes (n = 6). The radiochemical purity of the isolated radioligand was 99% and the specific activity was 100-150 GBq/micromol. In vitro characterization using ligand-binding assays demonstrated that [18F]-SB209670 bound with a single subnanomolar affinity to human heart tissue (n = 3) with a KD = 0.67 +/- 0.14 nM and a Bmax = 168.3 +/- 29.3 fmol/mg protein. The binding was time-dependent with a half-time (t(1/2)) for association of 3.8 minutes and an association rate constant (kobs) of 0.182 +/- 0.032/min. In vivo distribution in the rat was studied using microPET. Dynamic imaging revealed a fast clearance of [F]-SB209670 from the circulation by the liver, indicative of a high degree of metabolism. However, visualization of uptake in the rat heart was achievable and dynamic PET data together with the in vitro results suggest that [F]-SB209670 binds rapidly and primarily to endothelin-A receptors in the heart.

Influence of blood glucose level, age and fasting period on non-pathological FDG uptake in heart and gut

Increased, non-pathological FDG uptake in myocardium, stomach and bowel is frequently observed while performing clinical positron emission tomography (PET) studies. This "physiological" increased FDG uptake is not related to (oncological) disease and is unwanted since it may interfere with correct image reading. We evaluated the role of several patient-related factors that may have an influence on this phenomenon. One hundred and seventy-five non-diabetic patients with malignant diseases, referred to our department for routine whole-body FDG-PET, were retrospectively evaluated. Age, blood glucose levels and duration of the fasting period were recorded. FDG uptake in myocardium, bowel and stomach was visually graded. Statistical analysis showed that increased FDG uptake in myocardium, bowel and stomach was not significantly correlated to blood glucose level, age or duration of fasting. Most patients who underwent repeated PET scans (92 scans in 25 patients), showed no or minor changes in uptake in bowel and stomach on the consecutive scans, while myocardial uptake was more variable. Age, fasting period and blood glucose levels did not influence physiological uptake. However, there seemed to be a patient-specific pattern for stomach and bowel uptake.

Facile synthesis and initial PET imaging of novel potential heart acetylcholinesterase imaging agents [ 11C]pyridostigmine and its analogs

A series of 11C-labeled analogs of the acetylcholinesterase (AChE) inhibitor pyridostigmine have been synthesized for evaluation as new potential positron emission tomography (PET) imaging agents for heart AChE. The appropriate precursors for radiolabeling were slightly modified from commercial reagents. The new tracers [ 11C]pyridostigmine ( 1), [ 11C] para-pyridostigmine ( 2) and [ 11C] ortho-pyridostigmine ( 3) were prepared by N-[ 11C]methylation of the precursors using [ 11C]methyl triflate. Pure target compounds were isolated by a solid-phase extraction (SPE) purification procedure with 60–85% radiochemical yields (decay corrected to end of bombardment), and a synthesis time of 10–15 min. The initial PET dynamic studies of compounds ( 1– 3) in rat heart showed rapid heart uptake and blood pool clearance to give high quality heart images. These results suggest the new tracers delineate the heart very clearly and could be potential heart AChE imaging agents.

CARBON MONOXIDE ACTUATES O 2-LIMITED HEME DEGRADATION IN THE RAT BRAIN

The biochemical paradigm for carbon monoxide (CO) is driven by the century-old Warburg hypothesis: CO alters O 2-dependent functions by binding heme proteins in competitive relation to 1/oxygen partial pressure ( PO 2). High PO 2 thus hastens CO elimination and toxicity resolution, but with more O 2, CO-exposed tissues paradoxically experience less oxidative stress. To help resolve this paradox we tested the Warburg hypothesis using a highly sensitive gas-reduction method to track CO uptake and elimination in brain, heart, and skeletal muscle in situ during and after exogenous CO administration. We found that CO administration does increase tissue CO concentration, but not in strict relation to 1/ PO 2. Tissue gas uptake and elimination lag behind blood CO as predicted, but 1/ PO 2 vs. [CO] fails even at hyperbaric PO 2. Mechanistically, we established in the brain that cytosol heme concentration increases 10-fold after CO exposure, which sustains intracellular CO content by providing substrate for heme oxygenase (HO) activated after hypoxia when O 2 is resupplied to cells rich in reduced pyridine nucleotides. We further demonstrate by analysis of CO production rates that this heme stress is not due to HO inhibition and that heme accumulation is facilitated by low brain PO 2. The latter becomes rate limiting for HO activity even at physiological PO 2, and the heme stress leads to doubling of brain HO-1 protein. We thus reveal novel biochemical actions of both CO and O 2 that must be accounted for when evaluating oxidative stress and biological signaling by these gases.

The effect of glucose load on both cardiac and skeletal muscle FDG uptake

Background: The augmentation of the myocardial FDG uptake after a glucose load is very well established. However, the response of the skeletal muscle to the same glucose load has not been clearly demonstrated. The aim of this study is to demonstrate an increased skeletal muscle FDG uptake after a standard oral glucose load. To this end, we compared myocardial and skeletal muscle FDG uptake in a group of fasted patients to that of a second group of patients who underwent FDG PET scanning following oral glucose load. Methods: We included 41 patients (20 Male, 21 Female; age:26–72 years) without any cardiac pathology who had whole body FDG PET scan after several hours of fasting (4–24) in the first group. In the second group, we included 9 patients (8M; 1F; age 52–80 years) who had cardiac FDG PET imaging following a 50 g of oral glucose load. PET images were acquired with a Phillips Allegro scanner. We calculated the standard uptake values (SUV= Cts/injected dose/pt weight) of myocardium, arterial blood and skeletal muscle for both groups using regions of interest over the left ventricular myocardium, left ventricular cavity and skeletal muscle. Statistical analysis was performed using unpaired t test. Results: The results for both groups are given in table below. * Groups Heart SUV * Blood SUV Muscle SUV * Heart/Blood * Heart/Muscle Gp1 (n = 41) 4.8 ± 3.07 1.9 ± 0.64 0.88 ± 0.29 5.78 ± 3.70 2.54 ± 1.17 Gp2 (n = 9) 8.9 ± 5.25 2.39 ± 0.83 1.52 ± 0.50 6.62 ± 5.24 3.72 ± 1.70 * p < 0.05 There were statistically significant difference (p<0.05) between p values for heart and skeletal muscle uptake and for the heart to blood ratio. Conclusions: Both myocardial and skeletal muscle FDG uptake were higher in patients that received glucose load. However, the arterial concentration was similar. Skeletal muscle uptake could be used as an indicator of fasting status in patients undergoing FDG PET imaging.

Synthesis and first in vivo evaluation of new selective high affinity β 1-adrenoceptor radioligands for SPECT based on ICI 89,406

The results of cardiac biopsies suggest that myocardial β 1-adrenoceptor (AR) density is reduced in patients with chronic heart failure, while changes in cardiac β 2-ARs vary. A technique for visualization and quantification of β 1-AR populations rather than total β-AR densities in the human heart would be of great clinical interest. Molecular imaging techniques, either single photon emission computed tomography (SPECT) or positron emission tomography (PET), with appropriate radiopharmaceuticals offer the possibility to assess β-AR density noninvasively in humans, but to date, neither a SPECT nor a PET-radioligand is clinically established for the selective imaging of cardiac β 1-ARs. The aim of this study was to design a high affinity selective β 1-AR radioligand for the noninvasive in vivo imaging of cardiac β 1-AR density in man using SPECT. Based on the well-known selective β 1-AR antagonist, ICI 89,406, both the racemic iodinated target compound 11a and the ( S)-enantiomer 15a were synthesized. Competition studies using the nonselective AR ligand, [ 125I]iodocyanopindolol ([ 125I]ICYP), and ventricular membrane preparations from mice showed that 11a and 15a possess higher β 1-AR affinities (up to 265-fold) and β 1-AR selectivities (up to 245-fold) than ICI 89,406. Encouraged by these results, the radioiodinated counterparts of racemic 11a ( 11b: 125I, 11c: 123I) and ( S)-configurated 15a ( 15b: 125I, 15c: 123I) were synthesized. The target compounds were evaluated in rats. Biodistribution and metabolism studies in rats indicated that there is a specific heart uptake of 11b– c and especially 15b– c accompanied by rapid metabolism of the radioligands. Therefore, radioiodinated 11c and 15c appeared to be unpromising SPECT-radioligands for assessing β 1-ARs in vivo in the rat. However, the rat may metabolize β-AR ligands more rapidly than other species as demonstrated for ( S)-[ 11C]CGP 12177, a radioligand structurally related to 11a– c and 15a– c. Therefore further studies in a different animal model will be carried out.

Cardiac-specific Knock-out of Lipoprotein Lipase Alters Plasma Lipoprotein Triglyceride Metabolism and Cardiac Gene Expression

Fatty acids are the primary energy source for the heart. The heart acquires fatty acids associated with albumin or derived from lipoprotein lipase (LpL)-mediated hydrolysis of lipoprotein triglyceride (TG). We generated heart-specific LpL knock-out mice (hLpL0) to determine whether cardiac LpL modulates the actions of peroxisome proliferator-activated receptors and affects whole body lipid metabolism. Male hLpL0 mice had significantly elevated plasma TG levels and decreased clearance of postprandial lipids despite normal postheparin plasma LpL activity. Very large density lipoprotein-TG uptake was decreased by 72% in hLpL0 hearts. However, heart uptake of albumin-bound free fatty acids was not altered. Northern blot analysis revealed a decrease in the expression of peroxisome proliferator-activated receptor alpha-response genes involved in fatty acid beta-oxidation. Surprisingly, the expression of glucose transporters 1 and 4 and insulin receptor substrate 2 was increased and that of pyruvate dehydrogenase kinase 4 and insulin receptor substrate 1 was reduced. Basal glucose uptake was increased markedly in hLpL0 hearts. Thus, the loss of LpL in the heart leads to defective plasma metabolism of TG. Moreover, fatty acids derived from lipoprotein TG and not just albumin-associated fatty acids are important for cardiac lipid metabolism and gene regulation.

Synthesis and evaluation of N, N-dimethyl-2-(2-amino-5-[ 18F]fluorophenylthio)benzylamine (5-[ 18F]-ADAM) as a serotonin transporter imaging agent

The synthesis and evaluation of a new serotonin transporter (SERT) imaging agent, N, N-dimethyl-2-(2-amino-5-[ 18F]fluorophenylthio)benzylamine (5-[ 18F]-ADAM) is reported. Nucleophilic substitution of N, N-dimethyl-2-(2-nitro-5-bromophenylthio)benzylamine with K[ 18F]/Kryptofix 2.2.2 in DMSO at 125°C followed by reduction with NaBH 4–Cu(OAc) 2 in EtOH at 78°C and purification with HPLC produces the desired compound with an unoptimized yield of ∼5–10% in a synthesis time of 150 min from EOB. The biodistribution of 5-[ 18F]-ADAM in rats showed a high initial uptake and relatively rapid clearance in the brain (3.221±0.762, 0.440±0.059, 0.160±0.035 and 0.028±0.003% injected dose/organ at 2, 30, 60 and 120 min after I.V. injection, respectively) with the specific binding peaking at 1 h postinjection (hypothalamus/cerebellum and hippocampus/cerebellum were 2.97 and 3.59, respectively). The initial uptake in blood, lung, kidney and heart were also high, but it cleared rapidly. The radioactivity in the femur increased with time for 5-[ 18F]-ADAM indicating that in vivo defluorination may occur. Metabolism studies in rats showed that 5-[ 18F]-ADAM was not metabolized in rat brain, but was metabolized rapidly in the blood. Blocking experiments showed that there were significant decreases in the uptake of 5-[ 18F]-ADAM in the brain regions (hypothalamus, hippocampus and striatum) where SERT concentrations are high when rats were pretreated with (+)McN 5652 (2 mg/kg, 5 min prior to IV injection of 5-[ 18F]-ADAM). These results suggest that 5-[ 18F]-ADAM may be a potential new serotonin transporter PET imaging agent. However, due to its rapid wash-out from the brain, defluorination in vivo and lower uptake in the brain than 4-[ 18F]-ADAM, 5-[ 18F]-ADAM may not be as useful as 4-[ 18F]-ADAM as a SERT imaging agent.

Evaluation of anesthesia effects on [ 18F]FDG uptake in mouse brain and heart using small animal PET

This study evaluates effects of anesthesia on 18F-FDG (FDG) uptake in mouse brain and heart to establish the basic conditions of small animal PET imaging. Prior to FDG injection, 12 mice were anesthetized with isoflurane gas; 11 mice were anesthetized with an intraperitoneal injection of a ketamine/xylazine mixture; and 11 mice were awake. In isoflurane and ketamine/xylazine conditions, FDG brain uptake (%ID/g) was significantly lower than in controls. Conversely, in the isoflurane condition, %ID/g in heart was significantly higher than in controls, whereas heart uptake in ketamine/xylazine mice was significantly lower. Results suggest that anesthesia impedes FDG uptake in mouse brain and affects FDG uptake in heart; however, the effects in the brain and heart differ depending on the type of anesthesia used.

A Mathematical Observer Study for the Evaluation and Optimization of Compensation Methods for Myocardial SPECT Using a Phantom Population That Realistically Models Patient Variability

The goal of this study was to develop and apply a population of phantoms that realistically models patient variability and use it to optimize and evaluate different compensation methods used during reconstruction process with respect to defect detection in myocardial SPECT images. Various combinations of attenuation, detector response and scatter compensation were used in this study. A major difference between this and previous studies was that the level of realism was significantly increased by inclusion of variability in heart and organ uptakes, in the heart size and orientation, and in the defect size and contrast. In this study we used a population of 24 4-D NCAT phantoms (half male, half female) recently developed with statistical models for organ uptake and organ size based on clinical data. Almost noise-free projection data of the torso, heart, liver, lungs, and other organs were simulated for each phantom using the SIMSET MC simulation code. They were then combined to form 72 sets of projections for each phantom using randomly sampled activity ratios from a clinically realistic distribution. Poisson noise was then added to the projection data. We applied the channelized hotelling observer (CHO) and receiver operating characteristic (ROC) analysis to optimize iteration number for OSEM and cutoff frequency of a 3-D post-reconstruction Butterworth filter. We found that the area under the ROC curve (AUC) values were reduced compared to a previous study that included significantly less phantom variability, even though the defect contrast was higher and noise level was lower. The resulting AUC values were similar to those obtained using patient data. We found, in agreement with the previous study, that including compensation for more effects resulted in improved defect detectability. However, the optimal filter cutoff frequency was increased compared to the previous study. These studies demonstrate the importance of including realistic levels of phantom variability in myocardial perfusion studies using simulated data.

Highlights of the annual congress of the European Association of Nuclear Medicine, Amsterdam 2003.

no. Country Author Radiopharmaceutical Title 1106–326 Germany Kreissl 18F-FES and 18F-FTX Visualization of sex hormone and SERM uptake in the rat heart by PET P14–167 Switzerland Blagoev 18F-EF5 Radiosynthesis and PET studies of 18F-EF5 as a hypoxia imaging agent in dog patients with spontaneous tumors P26–358 Iran Jalilian 62Zn-bleomycin Preparation, distribution, stability and tumor imaging properties of [62Zn]bleomycin complex in normal and tumor-bearing mice P26–359 Germany Hofmann 68Ga-DOTANOC Feasibility of Ga-68-dotanoc PET 801–209 Germany Miyagawa 124I-FIAU PET assessment of [124I]-FIAU kinetics in rats following cardiac adenoviral transfer of the herpesviral thymidine kinase reporter gene (HSV1-tk)

1037 Breast cancer staging with 99mTc-tetrofosmin and 99mTc-MIBI: intraindividual comparison

The aim of this study was to compare uptake of 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-Q12 in vitro and biodistribution in vivo in rats. In vitro, uptake decreased in the order MIBI→tetrofosmin→Q12. Uptake of MIBI and tetrofosmin, but not of Q12, in cultured tumor cells was dependent on the plasma membrane and mitochondrial potential. In vivo, heart uptake of all three compounds was high and stable. Tumor uptake decreased in the order MIBI→Q12→tetrofosmin and the tumor/blood ratio in the order MIBI→tetrofosmin→Q12.

Effect of age on body distribution of Tityustoxin from Tityus serrulatus scorpion venom in rats

Previous research from our Laboratory has shown a greater susceptibility of young animals, when compared to adults, to envenomation by tityustoxin (TsTX), one of the main toxins from Tityus serrulatus scorpion venom. Our hypothesis is that a differential body distribution of TsTX among adult and young animals could account for the worse prognosis of scorpion envenomation in infants. Thus, TsTX labeled with technetium-99m was injected (6 μg, subcutaneous) in adult (150–160 day-old) and young (21–22 day-old) male rats. Groups of animals were sacrificed at different times after TsTX injection (0.08, 1.0, 3.0, 6.0, 12.0 and 24.0 hours) under Urethane anesthesia (140 mg/100 g, i.p.). The brain, heart, lungs, liver, kidneys, spleen and thyroid were excised and blood collected. Young rats presented a shorter latency toxin concentration peak in all studied organs except for the liver and the kidney, when compared to adults. The ratio between the area under the curve of the toxin concentration in each organ and that in blood (Kp) indicates higher accumulation in the organs of young animals mainly for brain, liver and heart. These observations suggest a faster toxin distribution in the organs of young rats. The higher uptake of TsTX in the brain is suggestive of a greater permeability for the toxin along the blood-brain barrier of young rats. In conclusion, the higher uptake in heart, together with data from the brain, may help to elucidate the clinical manifestations frequently observed in children under scorpion envenomation.

Effects of particle size on blood clearance and tissue uptake of lipid emulsions with different triglyceride compositions.

Particle size of IV lipid emulsions affects the catabolism of long-chain triglyceride (LCT) emulsions, but little is known about its effect on the catabolism of medium-chain triglyceride (MCT)- and fish oil (FO)-containing emulsions. Large (VLDL size), intermediate, and small (IDL size) emulsions with different triglyceride (TG) compositions were labeled with [3H]cholesteryl oleoyl ether: LCT (triolein 100%), MCT:LCT (trioctanoin:triolein 50%:50%), MCT:LCT:FO (trioctanoin:triolein:triDHA 50%:40%:10%), and FO (triDHA 100%). Emulsions (0.4 mg TG/mouse) were injected into C57BL/6J mice, and blood clearance and tissue uptake of emulsion particles were determined. Large emulsion particles had 2- to 3-fold faster fractional catabolic rates (FCR) compared with small particles with the same TG content. There was 1.5- to 2.0-fold higher FCR of large FO-containing emulsions (FO and MCT:LCT:FO) compared with large LCT and MCT:LCT emulsions, whereas effects of FO on FCR in small emulsions were not observed. Large FO-containing emulsions were taken up more by adipose tissue compared with small particles with concomitant decreases in hepatic uptake. Preinjection of heparin reduced heart and adipose uptakes of FO and MCT:LCT:FO emulsions with increased uptake by liver, suggesting a role of lipoprotein lipase in catabolism of FO-containing emulsions. In a mouse model, FO addition to large emulsions increased blood clearance and changed organ delivery. In contrast, there was no or little effect when particle size became smaller. We hypothesize that in humans, FO addition to lipid emulsions can help target emulsion delivery to certain extrahepatic tissues, a factor that may be of use for delivering specific fatty acids, or even drugs, to specific organs.