Validation of Tc-labeled “4+1” fatty acids for myocardial metabolism and flow imaging: Part 2. Subcellular distribution

IntroductionOur group has synthesized technetium-labeled fatty acids (FA) that are extracted into the myocardium and sequestered due to heart-type fatty acid binding protein (H-FABP) binding. In this article, we further address the detailed subcellular distribution and potential myocardial metabolism of [^99mTc]“4+1” FA.MethodsExperiments were conducted using isolated hearts of Wistar rats, as well as of wild-type and H-FABP^?/? mice. Myocardium samples underwent subcellular fractionation [subsarcolemmal mitochondria (SM), intermyofibrillar mitochondria (IM), cytosol with microsomes, and nuclei and crude membranes] and analysis by thin-layer chromatography and high-performance liquid chromatography.ResultsThe largest fraction of tissue radioactivity was associated with cytosol [79.69±8.88% of infused dose]. About 9.07±0.95% and 3.43±1.38% of the infused dose were associated with SM and IM fractions, respectively. In the rat heart, etomoxir, an inhibitor of carnitin-palmitoyl transferase I, did not significantly decrease radioactivity associated with mitochondrial fractions, whereas myocardial extraction of [¹²³I]-labeled 15-(p-iodophenyl)-pentadecanoic acid (13.26% vs. 49.49% in controls) and the radioactivity associated with the SM and IM fractions were blunted. The percentage of the infused dose in the mitochondrial and crude fractions increased with the number of NH-amide groups of the FA derivative. Absence of H-FABP significantly decreased radioactivity count in the cytosolic fraction (P<.001). No metabolic product of [^99mTc]“4+1” FA could be detected in any isolated heart.ConclusionsMyocardial [^99mTc]“4+1” FA extraction reflects binding to H-FABP and membrane structures (including the mitochondrial membrane). However, the compounds do not undergo mitochondrial metabolism because they do not reach the mitochondrial matrix.     

Ventricular muscarinic receptor remodeling in patients with and without primary ventricular fibrillation. An imaging study

Background

Vagal innervation modulates the electrical stability of the left ventricle (LV) during ischemia. Thus, abnormal parasympathetic activity in myocardial infarction (MI) patients with primary ventricular fibrillation (FV) can account for their arrhythmic disorders. We evaluated LV muscarinic receptor density (B _max) after MI in patients with (FV_G, n?=?11) or without (nFV_G, n?=?12) primary FV.

Methods and Results

The B _max was measured by positron emission tomography and the specific antagonist [¹¹C]methylquinuclidinyl benzilate ([¹¹C]MQNB) in 23 patients 39?±?19?days post-MI, and 10 volunteers. Myocardial damage was quantified by delayed contrast-enhanced magnetic resonance imaging. Three short-axis slices per subject were analyzed and six time-activity curves per slice were fitted to a 3-compartment ligand-receptor model. The B _max in remote regions of the 23 patients (67?±?36?pmol/mL?·?tissue; n?=?139) was higher than in normal regions of volunteers (33?±?16?pmol/mL?·?tissue; n?=?171; P?=?.01). Receptor density in remote regions was similarly upregulated in nFV_G (69?±?31?pmol/mL?·?tissue, n?=?73) and FV_G (66?±?40?pmol/mL?·?tissue, n?=?66; P?=?.72). In damaged regions, the B _max was reduced in both patient groups (44?pmol/mL?·?tissue).

Conclusions

Chronically infarcted patients with or without primary FV share similar patterns of ventricular muscarinic receptor remodeling, characterized by receptor upregulation, in remote non-damaged territories.     

Evaluation of a multicrystal gamma camera and rotating chair for tomographic studies of the heart

Background

This study evaluates the feasibility of performing tomographic studies with a multicrystal gamma camera combined with a rotating chair.

Methods and Results

Tomographic acquisitions were performed with a cardiac phantom containing eight defects of different sizes. Defect size was determined from the fraction of counts in the short-axis slices that fell below a fixed threshold value. Image contrast was determined from the ratio of minimum/maximum counts. Images of an American College of Nuclear Physicians cardiac single-photon emission computed tomographic phantom were acquired and the results were compared with those obtained from 194 centers in the United States. For cardiac studies with ²⁰¹TI and ^99mTc, threshold values of 65% to 70% gave the best correlation (R ²>0.94) between true and measured defect sizes, although the slope of the regression line was less than 0.95 for both isotopes. Small inferior defects demonstrated poor image contrast, particularly for ^99mTc. Of the three defects in the American College of Nuclear Physicians phantom, the two largest were identified in the tomographic images.

Conclusions

A multicrystal gamma camera system coupled with a rotating chair can be used for tomographic studies of the heart. Image quality is poorer than that seen on conventional single-photon emission computed tomographic systems, particularly for ^99mTc.     

Synthesis and characterization of [76Br]-labeled high-affinity A3 adenosine receptor ligands for positron emission tomography

IntroductionBromine-76-radiolabeled analogues of previously reported high-affinity A₃ adenosine receptor (A₃AR) nucleoside ligands have been prepared as potential radiotracers for positron emission tomography.MethodsThe radiosyntheses were accomplished by oxidative radiobromination on the N⁶-benzyl moiety of trimethyltin precursors. Biodistribution studies of the kinetics of uptake were conducted in awake rats.ResultsWe prepared an agonist ligand {[⁷⁶Br](1′S,2′R,3′S,4′R,5′S)-4′-{2-chloro-6-[(3-bromophenylmethyl)amino]purin-9-yl}-1′-(methylaminocarbonyl)bicyclo[3.1.0]hexane-2′,3′-diol (MRS3581)} in 59% radiochemical yield with a specific activity of 19.5 GBq/μmol and an antagonist ligand {[⁷⁶Br](1′R,2′R,3′S,4′R,5′S)-4′-(6-(3-bromobenzylamino)-2-chloro-9H-purin-9-yl)bicyclo[3.1.0]hexane-2′,3′-diol (MRS5147)} in 65% radiochemical yield with a specific activity of 22 GBq/μmol. The resultant products exhibited the expected high affinity (K_i～0.6 nM) and specific binding at the human A₃AR in vitro. Biodistribution studies in the rat showed uptake in the organs of excretion and metabolism. The antagonist MRS5147 exhibited increasing uptake in testes, an organ that contains significant quantities of A₃AR, over a 2-h time course, which suggests the presence of a specific A₃AR retention mechanism.ConclusionWe were able to compare uptake of the [⁷⁶Br]-labeled antagonist MRS5147 to [⁷⁶Br]agonist MRS3581. The antagonist MRS5147 shows increasing uptake in the testes, an A₃AR-rich tissue, suggesting that this ligand may have promise as a molecular imaging agent.     

Preliminary studies of (99m)Tc-memantine derivatives for NMDA receptor imaging

IntroductionNovel technetium-labeled ligands, ^99mTc-NCAM and ^99mTc-NHAM were developed from the N-methyl-d-aspartate (NMDA) receptor agonist memantine as a lead compound by coupling with N₂S₂. This study evaluated the binding affinity and specificity of the ligands for the NMDA receptor.MethodsLigand biodistribution and uptake specificity in the brain were investigated in mice. Binding affinity and specificity were determined by radioligand receptor binding assay. Three antagonists were used for competitive binding analysis. In addition, uptake of the complexes into SH-SY5Y nerve cells was evaluated.ResultsThe radiochemical purity of ^99mTc-labeled ligands was more than 95%. Analysis of brain regional uptake showed higher concentration in the frontal lobe and specific uptake in the hippocampus. ^99mTc-NCAM reached a higher target to nontarget ratio than ^99mTc-NHAM. The results indicated that ^99mTc-NCAM bound to a single site on the NMDA receptor with a K_d of 701.21 nmol/l and a B_max of 62.47 nmol/mg. Specific inhibitors of the NMDA receptor, ketamine and dizocilpine, but not the dopamine D₂ and 5HT_1A receptor partial agonist aripiprazole, inhibited specific binding of ^99mTc-NCAM to the NMDA receptor. Cell physiology experiments showed that NCAM can increase the viability of SH-SY5Y cells after glutamate-induced injury.ConclusionsThe new radioligand ^99mTc-NCAM has good affinity for and specific binding to the NMDA receptor, and easily crosses the blood–brain barrier; suggesting that it might be a potentially useful tracer for NMDA receptor expression.     

The role of lower extremity joint powers in successful stair ambulation

Ascending stairs is an important functional activity that is affected by lower extremity pathology including amputation. Although several studies have demonstrated stair ascent is more challenging than level ground walking, our understanding of the mechanics remains limited. The purpose of this study was to determine the association between lower extremity joint power generation and vertical COM acceleration (COM_A) during stair ascent. Twenty-two healthy individuals underwent a biomechanical gait assessment while walking up a 16-step instrumented staircase. The association between the peak joint powers and peak COM_A during stance were assessed with respect to timing and magnitude. With respect to timing, peak ankle joint power was highly correlated with peak COM_A (R² = 0.93), while peak knee and hip joint powers demonstrated limited association with COM_A (R² = 0.41 and 0.08, respectively). Only the magnitude of peak ankle power was associated with peak COM_A (R² = 0.3).Significant temporal and magnitude associations between peak ankle joint power and peak COM_A suggest ankle power is a key contributor to COM_A. Although peak knee joint power and COM_A are temporally associated, the association is weaker and the occurrence of peak joint knee power is nearly 10% after peak COM_A, suggesting knee joint power plays a lesser role in COM_A. These combined findings indicate the role of trail limb ankle plantarflexors should be recognized in the stair ascent cycle definition and demonstrate the potential importance of a power generated by the ankle plantarflexors to normalize stair ascent performance following lower extremity amputation.     

Cortical perfusion response to an electrical stimulation of the auditory nerve in profoundly deaf patients: study with technetium-99m hexamethylpropylene amine oxime single photon emission tomography

Brain activation procedures associated with single photon emission tomography (SPET) have recently been developed in healthy controls and diseased patients in order to help in their diagnosis and treatment. We investigated the effects of a promontory test (PT) on the cerebral distribution of technetium-99m hexamethylpropylene amine oxime (^99mTc-HMPAO) in 7 profoundly deaf patients, 6 PT + and one PT-. The count variation in the temporal lobe was calculated on 6 coronal slices using the ratio (R_stimulation— R_deprivation)/R_deprivation where R=counts in the temporal lobe/whole-brain count. A count increase in the temporal lobe was observed in all patients and was higher in all patients with PT + than in the patient with PT-. The problems of head positioning and resolution of the system were taken into account, and we considered that the maximal count increment was related to the auditory cortex response to the stimulus. Further clinical investigations with high-resolution systems have to be performed in order to validate this presurgery test in cochlear implant assessment.     

Estimation of regional lung function in interstitial pulmonary disease using 99mTc-Technegas and 99mTc-macroaggregated albumin single-photon emission tomography

For quantitative evaluation of the regional lung function in patients with interstitial pulmonary disease (IP) in the sitting position, ^99mTc-Technegas and ^99mTc-macroaggregated albumin (MAA) single-photon emission tomography (SPET) studies were performed in 12 healthy controls (HC) and 42 IP patients. Four transverse images were prepared from the data obtained and designated as slices no. 1–4 from the top downward. Regions of interest (ROIs) were determined in the anterior and posterior parts of the lung in each slice, and the ratio of the count per voxel in the ROIs to the count in the entire lung was calculated as the regional Technegas index (T). The regional perfusion index (Q) was calculated by a similar procedure using the data of ^99mTc-MAA SPET. The ratios between T and Q (T/Q) in the anterior and posterior regions of the lung, and the ratios of T and Q between the anterior and posterior regions of the lung (Tp/Ta and Qp/Qa) were examined. In the HC group, T/Q decreased but Tp/Ta and Qp/Qa increased from the upper to the lower lung fields. When IP patients were classified into (I) those in whom T/Q decreased from the upper to the lower lung fields, (II) those in whom it was similar in all slices, (III) those in whom it increased from slice 3 to slice 4, and (IV) those in whom it increased from slice 2 to slices 3 and 4, this classification was more closely correlated with %VC than with %DL_CO or PaO₂. When the patients were classified according to Tp/Ta and Qp/Qa into (A) those in whom the values were greater in the lower than the upper lung field, (B) those in whom the values were similar in all slices, and (C) those in whom the values were smaller in lower than in upper lung fields, categories B and C were observed frequently even in patients whose %VC was in the normal range. This method is considered to be an effective means to evaluate the progression and pathology of IP and to detect early impairment of lung function. Received 1 May and in revised form 15 August 1998     

Prediction of postoperative pulmonary function: preliminary comparison of single-breath dual-energy xenon CT with three conventional methods

Purpose

To assess the use of xenon ventilation maps (Xe-images) for predicting postoperative pulmonary function.

Materials and methods

After study approval by the institutional review board, written informed consent was obtained from 30 patients with lung tumors who underwent pre- and postoperative spirometry, pulmonary perfusion SPECT and dual-energy CT (80 kV and 140 kV/Sn) after single-breath inspiration of 35 % xenon. Xe-images were calculated by three-material decomposition. Sum of pixel values of the part to be resected (A) and of the whole lung (B) on Xe-images or lung perfusion SPECT, and volumes or the number of segments of the part to be resected (A) and of the whole lung (B) on Xe-images were enumerated, respectively. We multiplied (1 ? A/B) by each preoperative value from spirometry for prediction. Predictions by each of the four methods were compared with postoperative values.

Results

Predicted values for vital capacity (VC), forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV₁) by the four methods regressed significantly with measured values (R ² = 0.56–0.77, p < 0.001 for all).

Conclusion

Analysis of Xe-images can predict postoperative VC, FVC and FEV₁ with accuracy comparable to that of CT volumetry.     

Influence of patient height and weight and type of stress on myocardial count density during SPECT imaging with thallium-201 and technetium 99m-sestamibi

Background  The aim of this study was to determine the variability in myocardial activity with 99mTc-labeled sestamibi and 201Tl tomographic imaging, and to correlate this variability with patient anthropometric data and type of stress. Methods and Results  Conventional tomographic acquisition (all-purpose collimator, 30 views, 40 sec/view) was performed in 249 patients (155 with 99mTc-sestamibi, 84 with 201TI). Normal myocardium was identified in three short-axis tomographic slices between the base and mid-ventricle. To exclude abnormal myocardium, all myocardial activity below and 85% threshold of peak counts was excluded. The average counts per pixel in the remaining myocardium was determined. All data were normalized to a collimator sensitivity of 8.1 counts/min/kBq and corrected for decay. Myocardial count densities in both 201TI and 99mTc-sestamibi studies exhibited a high degree of variability and varied by factors of 3 to 4 and 2.5 to 3 respectively, between the 10th and 90th percentile of count densities. All 99mTc-sestamibi studies showed an inverse correlation (R≈0.7) between myocardial count density and patient weight. For stress 201TI studies in male patients, a similar inverse correlation (R=0.63) was found between patient weight and myocardial count density. No correlation was found for female patients. For rest 99mTc-sestamibi studies, the average myocardial count density was 1245±297 counts/pixel for a 1.11 GBq (30 mCi) injection. This was similar with pharmacologic stress (1224±297 counts/pixel per 1.11 GBq (30 mCi), but significantly higher with exercise (1569±363 counts/pixel per 1.11 GBq (30 mCi) (p<0.005). 201TI studies averaged 327±97 counts/pixel (111 MBq [3 mCi] injection) with exercise and 374±145 counts/pixel/111 MBq (3 mCi) with pharmacologic stress (p=NS). Redistribution studies after exercise/pharmacologic stress (with a 37 MBq [1 mCi] reinjection) averaged 267±83 counts/pixel (148 MBq [3+1 mCi]). Conclusion  Measured count densities in the myocardium demonstrate a high degree of variability that is only weakly correlated with patient anthropometric data. Nevertheless, knowledge of the mean values of myocardial activity as a function of administered dose may be useful in the optimization of rapid imaging procedures for 99mTc-based perfusion agents.     

Myocardial adenosine A2a receptor imaging of rabbit by PET with [11C]KF17837

Adenosine A_2a receptors are found in the endothelia, vascular smooth muscle cells and cardiac myocytes. The properties of a carbon-11 labeled A_2a antagonist [¹¹C]KF17837 ([7-methyl-¹¹C](E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine) for myocardial imaging were evaluated by dynamic PET scanning of the myocardium in rabbits. Myocardial uptake of [¹¹C]KF17837 was clearly visualized by PET. The tracer was taken up at a high level by the myocardium immediately after the injection, and the myocardial level of radioactivity gradually decreased. On the other hand, an inactive [¹¹C]Z-isomer of [¹¹C]KF17837 showed a very low myocardial uptake and the myocardium was not visualized with a selective A₁ antagonist [¹¹C]KF15372. By co-injection with carrier KF17837 or a xanthine type A_2a antagonist 7-chlorostyrylcaffeine (CSC), the myocardial uptake of [¹¹C]KF17837 was completely blocked. The effect of non-xanthine A_2a antagonists ZM 241385 and SCH 58261, which have a higher affinity than CSC, was smaller than that of the CSC. The effect of weak antagonists caffeine and alloxazine or a xanthine type A₁ antagonist KF15372 on the radioactivity level was small. It is concluded that PET with [¹¹C]KF17837 can image myocardial adenosine A_2a receptors.     

Slice-by-slice B(1) (+) shimming at 7 T

Parallel transmission has been used to reduce the inevitable inhomogeneous radiofrequency fields produced in human high‐field MRI greater than 3 T. Further improvements in the transmit homogeneity and efficiency are possible by leveraging the additional degree of freedom permitted by multislice acquisitions. Compared to simple scaling of the flip angle to compensate for B₁⁺ falloff along the radiofrequency coil, calculation of B₁⁺ shim solutions on a slice‐by‐slice basis can markedly improve homogeneity and/or reduce transmitted power and global SAR. Performance measures were acquired at 7 T with a 15‐channel head‐only transceive array featuring elements distributed over all three logical axes, facilitating B₁⁺ shimming over arbitrary orientations. Compared to a circularly polarized volume mode of the same coil, shimming to maximize excitation efficiency on a slice‐by‐slice basis yielded improvements in mean B₁⁺ by 12.8 ± 2.4% and a reduction in standard deviation of B₁⁺ of 16.3 ± 6.8%, while reducing relative SAR by 6.2 ± 3.1%. When shimming for greater uniformity, the mean and standard deviation of B₁⁺ were further improved by 15.9 ± 2.6% and 26.2 ± 10.4%, respectively, at the expense of a 135 ± 8% increase in global SAR. Robust multislice‐shim solutions are demonstrated that can be quickly calculated, applied in real time, and reliably improve on volume coil modes. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Determination of 99mTc valent form in solids by measurement of internal conversion electrons

The core-level internal conversion electron spectroscopy (ICES) was used to study no-carrier-added compounds of ^99mTc in the form of solid deposits. The following chemical shifts of the electron binding energies were determined: ΔE_B(NH₄TcO₄NaTcO₄) = 0.0±0.3 eV, ΔE_B(NH₄TcO₄TcO₂·2H₂ O) = 3.±0.3 eV. Furthermore, two valent forms were distinguished in the decay-induced ^99mTc species created from the Na₂⁹⁹MoO₄ in the NaOH matrix. The smallest detectaable amount of ^99mTc in the minor valent form was ∼30μCi (6 × 10⁻¹²g). The observed shifts ΔE_B(NH₄TcO₄NaTcO_x) = ±0.0±3 eV and ΔE_B(Nh₄TcO₄-NaTcO_y) = 2.1±0.3 eV indicate the chemical form NaTc(VII)O₄ for the NaTcO_x and either Na₂Tc(Vi) or NaTc(V0O₃ for the NaTcO_y. Shift calculations based on the ground -state potential model prefer NaTcO₃.     

<Emphasis Type="Italic">N</Emphasis>-isopropyl-4-[<Superscript>123</Superscript>I]iodoamphetamine (<Superscript>123</Superscript>I-IMP) products: a difference in radiochemical purity,unmetabolized fraction,and octanol extraction fraction in arterial blood and regional brain uptake in rats

N-isopropyl-4-[¹²³I]iodoamphetamine (¹²³I-IMP) is a lipophilic compound utilized for cerebral blood flow (CBF) measurement with single photon emission computed tomography (SPECT). Two different ¹²³I-IMP products (IMP_A and IMP_B) are commercially available. We examined the radiochemical purity, unmetabolized fraction, and octanol extraction fraction in arterial blood, and the regional brain uptake of IMP_A and IMP_B in a rat model. IMP_B (96.4% ± 0.08%, P < 0.05) showed significantly higher radiochemical purity than IMP_A (95.5% ± 0.20%). The mean unmetabolized fraction in arterial blood taken at 10 min after intravenous administration of IMP_B (69.5% ± 4.4%, P < 0.01) was significantly higher than that of IMP_A (59.6% ± 2.6%). The mean octanol extraction fraction of IMP_B (75.0% ± 1.3%, P < 0.01) was also significantly higher than that of IMP_A (67.2% ± 0.8%). The mean levels of radioactivity in arterial blood sampled at 10 min after injection and mean regional brain radioactivity (cerebral cortices, basal ganglia, brain stem, and cerebellum) at 10–12 min after injection were not significantly different between IMP_A and IMP_B. The present study indicates differences in the radiochemical purity and the unmetabolized and octanol extraction fraction in arterial blood between the two commercially available ¹²³I-IMP products. The appropriate octanol extraction fractions for IMP_A and IMP_B should be determined in humans and employed for quantitative CBF measurement in clinical SPECT.     

In vivo quantitative three-dimensional motion mapping of the murine myocardium with PC-MRI at 17.6 T.

This work presents a method that allows for the assessment of 3D murine myocardial motion in vivo at microscopic resolution. Phase-contrast (PC) magnetic resonance imaging (MRI) at 17.6 T was applied to map myocardial motion in healthy mice along three gradient directions. High-resolution velocity maps were acquired at three different levels in the murine myocardium with an in-plane resolution of 98 mum, a slice thickness of 0.6 mm, and a temporal resolution of 6 ms. The applied PC-MRI method was validated with phantom experiments that confirmed the correctness of the method with deviations of <1.7%. Myocardial in-plane velocities between 0.5 cm/s and 2.2 cm/s were determined for the healthy murine myocardium. Through-plane velocities of 0.1-0.83 cm/s were measured. Velocity data was also used to calculate the myocardial twist angle during systole at different slices in the short-axis view.     

Comparison of reinjection thallium 201 and resting technetium 99m sestamibi tomographic images for the quantification of infarct size after acute myocardial infarction

Background

Both thallium 201 and technetium 99m sestamibi have been used to quantitate infarct size at rest. Exercise²⁰¹Tl scintigraphy has been shown to have powerful prognostic information after myocardial infarction. A single study using these agents that could provide data on infarct size and prognosis would be of value. The purpose of this study was to compare estimates of infarct size by use of²⁰¹Tl and^99mTc sestamibi and to correlate these measurements with left ventricular ejection fraction in patients after acute myocardial infarction.

Methods and Results

The study group consisted of 20 patients who underwent low-level²⁰¹Tl stress studies with reinjection and^99mTc sestamibi resting studies within 4 days. Acute reperfusion was attempted in 18 of 20 patients. For^99mTc sestamibi tomographic imaging, infarct size was quantitated with 60% of maximal counts per slice for five short-axis slices as described in multiple previous studies. The postreinjection delayed²⁰¹Tl images acquired 4 hours after stress were quantitated according to the same threshold method.²⁰¹Tl patient images were also quantitated with a commercially available polar map program and compared with sex-matched control subjects. Ejection fraction was determined for each patient by radionuclide ventriculography 6 weeks later. Ejection fraction was well preserved for the group: mean 0.53±0.10. Infarct size with^99mTc sestamibi was 12%±13% of the left ventricle, which was significantly smaller than either method with²⁰¹Tl: threshold method, 29%±18% of left ventricle; polar map method, 25%±17% of left ventricle (both²⁰¹Tl estimates,p<0.0001 vs^99mTc sestamibi;²⁰¹Tl, 70% threshold vs²⁰¹Tl polar map,p=0.04). There was a significant correlation between infarct size with^99mTc sestamibi and that with²⁰¹Tl (r=0.72 to 0.73;p<0.001). Infarct size with^99mTc sestamibi, however, provided the closest correlation with ejection fraction (r=0.81;p<0.001), with the two²⁰¹Tl quantitative methods providing very similar correlations (r=0.69;p<0.001).

Conclusions

Infarct size with reinjection²⁰¹Tl imaging correlates significantly with resting infarct size with^99mTc sestamibi, although it provides significantly larger estimates. Although both approaches can be combined with a same-day exercise protocol, the closer correlation of infarct size with ejection fraction at 6 weeks suggests that resting infarct size with^99mTc sestamibi may be slightly more accurate.     

Acetazolamide induced myocardial ischemia in patients with severe coronary artery disease

Acetazolamide (ACZ)-augmented brain SPECT is commonly used for evaluating cerebral vascular reserve in patients with cerebrovascular disease. ACZ may cause myocardial ischemia in patients with coronary artery disease. To evaluate the risk of induction of myocardial ischemia with ACZ-augmented myocardial SPECT, we performed combined ACZ-augmented Tl-201 myocardial SPECT (ACZ-myo SPECT) with Tc-99m HMPAO brain SPECT in patients with severe coronary artery disease.Methods: Nine patients underwent combined ACZ-myo SPECT with Tc-99m HMPAO brain SPECT. (1) For qualitative analysis, SPECT images were divided into 13 segments to calculate the total defect scores. (2) Six ROIs were placed on the slices in the myocardial SPECT short-axis images and the regional uptake ratio was obtained as the ratio of the mean counts in the myocardium to the maximal count in the slice. The total defect score and regional uptake ratio of ACZ-myo SPECT were compared with those of early and delayed dipyridamole T1-201 myocardial SPECT (DP-T1 SPECT) images.Results: (1) In the 21 coronary artery territories with coronary stenosis ≧ 75%, the total defect score in ACZ-myo SPECT, early and delayed DP-T1 SPECT images were 3.52 ± 4.14*, 4.19 ± 4.65* and 2.25 ± 3.34, respectively (*: p < 0.05 vs. delayed DP-Tl SPECT images). (2) In 44 of 54 ROIs with coronary stenosis ≧75%, the regional uptake ratio of ACZ-myo SPECT, early and delayed DP-Tl SPECT images were 0.670 ± 0.166**, 0.677 ± 0.194**, 0.721 ± 0.178, respectively (**: p < 0.01 vs. delayed DP-Tl SPECT images). Systolic blood pressure fell at 11 min after ACZ infusion without electrocardiographic ST-T changes or chest pain.Conclusion: As ACZ has the potential to cause myocardial ischemia, ACZ-augmented brain SPECT should be performed with caution in patients with severe coronary artery disease associated with cerebrovascular disease.     

Pharmacokinetic analysis of [18F]FAZA in non-small cell lung cancer patients

Purpose

[¹⁸F]Fluoroazomycin arabinoside (FAZA) is a positron emission tomography (PET) tracer developed to enable identification of hypoxic regions within a tumour. The aims of this study were to determine the optimal kinetic model along with validation of using alternatives to arterial blood sampling for analysing [¹⁸F]FAZA studies and to assess the validity of simplified analytical methods.

Methods

Dynamic 70-min [¹⁸F]FAZA PET/CT scans were obtained from nine non-small cell lung cancer patients. Continuous arterial blood sampling, together with manual arterial and venous sampling, was performed to derive metabolite-corrected plasma input functions. Volumes of interest (VOIs) were defined for tumour, healthy lung muscle and adipose tissue generating [¹⁸F]FAZA time-activity curves (TACs). TACs were analysed using one- and two-tissue compartment models using both metabolite-corrected blood sampler plasma input functions (BSIF) and image-derived plasma input functions (IDIF).

Results

The reversible two-tissue compartment model with blood volume parameter (2T4k+V_B) best described kinetics of [¹⁸F]FAZA in tumours. Volumes of distribution (V_T) obtained using IDIF correlated well with those derived using BSIF (R ²?=?0.82). Venous samples yielded the same radioactivity concentrations as arterial samples for times >50 min post-injection (p.i.). In addition, both plasma to whole blood ratios and parent fractions were essentially the same for venous and arterial samples. Both standardised uptake value (SUV), normalised to lean body mass, and tumour to blood ratio correlated well with V_T (R ²?=?0.77 and R ²?=?0.87, respectively, at 50–60 min p.i.), although a bias was observed at low V_T.

Conclusion

The 2T4k+V_B model provided the best fit to the dynamic [¹⁸F]FAZA data. IDIF with venous blood samples can be used as input function. Further data are needed to validate the use of simplified methods.     

Evaluation of potential heart affine compounds by use of the isolated perfused rat heart

^99mTc-organocation complexes were screened for heart affinity using the isolated perfused rat heart. The ^99mTc-I compounds are better extracted by the heart and retained in it than the ^99mTc-III compounds. ^99mTcCl₂(DMPE) ₂ ⁺ shows low uptake (15%) and fast washout, but no impairment of uptake after incubation with human serum albumin(HSA), with a modified preparation, initial uptake is not much better (18%) but washout is clearly diminished. ^99mTc(DMPE) ₃ ⁺ is taken up to a greater extent (33%) if administered solely, but when given in conjunction with HSA, uptake decreases to about 4% because of strong affinity of the complex to the protein, but this compound persists well in the tissue. Detergents like tween 80 and dioctylsulphosuccinate are able to cause higher uptake of ^99mTc(DMPE) ₃ ⁺ even in the presence of HSA, thus indicating a diminished binding of the compound to the protein. ^99mTc(CN-t-butyl) ₆ ⁺ shows very high uptake (80%) by the heart, which is only moderately diminished by addition of HSA (t0 38%), and persists excellently in the myocardium.Basic features of the compounds such as accumulation in and elimination from the myocardium as well as plasma protein binding and their mutual relationships are well reflected by the isolated heart model.