Quantitation of iodine-123 MIBG uptake by normal adrenal medulla in hypertensive patients

Eighteen hypertensive patients with a clinical suspicion of pheochromocytoma and raised or borderline raised plasma catecholamine and urinary vanillyl mandelic acid (VMA) levels were studied by scintigraphy using 123I-labeled metaiodobenzylguanidine (MIBG). None of these patients had any scintigraphic evidence of pheochromocytoma at the time of study or on subsequent clinical follow-up. A quantitative approach was taken to calculate the adrenal medullary uptake of [123I]MIBG in these patients. Three different methods of quantitation were evaluated using data acquired from an anthropomorphic phantom and analysed by three independent observers. In the patient studies 34 out of 35 adrenal medullas were visualized with uptake in the range of 0.01-0.22% of the administered dose 22 hr postinjection which was calculated using the preferred quantitation method. This is an appropriate control group range for comparison with patients who have proven norepinephrine and epinephrine secreting tumors. A quantitative approach to [123I]MIBG imaging provides an important tool for studying adrenomedullary pathophysiology.     

Increased iodine-123-iodoamphetamine uptake in hepatomas

In the current study, two cases of hepatoma are reported in which N-isopropyl-(I-123)-p-iodoamphetamine (IMP) liver scan demonstrated increased accumulation in the tumor corresponding to the areas enhanced on contrast enhanced CT (CE-CT). In contrast, there was no IMP accumulation in the necrotic area of the tumor in which no enhancement was found on CE-CT. Thus, IMP liver scan seems to have the potential to assess the viability of a hepatoma as well as to detect and localize it.     

Comparison of iodine-123 epidepride and iodine-123 IBZM for dopamine D2 receptor imaging in clinically non-functioning pituitary macroadenomas and macroprolactinomas

We compared pituitary iodine-123 epide- pride single-photon emission tomography (SPET) and ¹²³I-IBZM SPET for the in vivo imaging of dopamine D₂ receptors in 15 patients with clinically non-functioning pituitary adenomas. Four patients with dopamine agonist-sensitive macroprolactinomas were studied as positive controls. The uptake of radioactivity in the pituitary was established using a visual scoring system and an uptake index calculated by dividing the average count rates in the pituitary area by the average count rates in the cerebellum. All four macroprolactinomas showed specific binding of ¹²³I-epidepride, but only one showed specific binding of ¹²³I-IBZM. Specific binding of ¹²³I-epidepride was demonstrated in 9 of the 15 clinically non-functioning pituitary adenomas (60%), but specific binding of ¹²³I-IBZM was shown in only 6 of these 15 cases (40%). The uptake of ¹²³I-epidepride in the pituitary region was consistently higher than that of ¹²³I-IBZM. None of the patients who showed absence of uptake of ¹²³I-epidepride in the pituitary area showed uptake of ¹²³I-IBZM in this area. In conclusion: ¹²³I-epidepride SPET is superior to ¹²³I-IBZM SPET for the visualization of dopamine receptor-positive pituitary adenomas. Therefore, ¹²³I-epidepride should replace ¹²³I-IBZM for future D₂ receptor SPET studies of pituitary adenomas. ¹²³I-epidepride SPET potentially might serve to predict the response of clinically non-functioning pituitary adenomas to dopamine agonist therapy. Received 11 July and in revised form 25 September 1998     

A kit formulation for preparation of iodine-123-IBZM: a new CNS D-2 dopamine receptor imaging agent.

A method for the preparation of iodine-123IBZM, a central nervous system D-2 imaging agent, is reported. By using a rapid filtration technique to remove the unreacted iodide, the preparation can be completed in less than 20 min (overall yield greater than 60%). The product, with high purity (greater than or equal to 95%) and specific activity, is suitable for human use.     

Multivariate cluster analysis of dynamic iodine-123 iodobenzamide SPET dopamine D2 receptor images in schizophrenia

This paper describes the application of a multivariate statistical technique to investigate striatal dopamine D₂ receptor concentrations measured by iodine-123 iodobenzamide (¹²³I-IBZM) single-photon emission tomography (SPET). This technique enables the automatic segmentation of dynamic nuclear medicine images based on the underlying time-activity curves present in the data. Once the time-activity curves have been extracted, each pixel can be mapped back on to the underlying distribution, considerably reducing image noise. Cluster analysis has been verified using computer simulations and phantom studies. The technique has been applied to SPET images of dopamine D₂ receptors in a total of 20 healthy and 20 schizophrenic volunteers (22 male, 18 female), using the ligand¹²³I-IBZM. Following automatic image segmentation, the concentration of striatal dopamine D₂ receptors shows a significant left-sided asymmetry in male schizophrenics compared with male controls. The mean left-minus-right laterality index for controls is −1.52 (95% CI −3.72−0.66) and for patients 4.04 (95% CI 1.07−7.01). Analysis of variance shows a caseby-sex-by-side interaction, withF=10.01,P=0.005. We can now demonstrate that the previously observed male sex-specific D₂ receptor asymmetry in schizophrenia, which had failed to attain statistical significance, is valid. Cluster analysis of dynamic nuclear medicine studies provides a powerful tool for automatic segmentation and noise reduction of the images, removing much of the subjectivity inherent in region-of-interest analysis. The observed striatal D₂ asymmetry could reflect long hypothesized disruptions in dopamine-rich cortico-striatallimbic circuits in schizophrenic males.     

Measurement of iodine-123 thyroid uptake using a gamma camera with LEAP collimator.

OBJECTIVE: This study compared the 123I thyroid uptake measurements obtained from a gamma camera fitted with a low-energy all-purpose (LEAP) collimator to those obtained from a thyroid uptake probe and gamma camera fitted with a pinhole (PH) collimator. METHODS: Thirty-one patients (27 female and 4 male patients) were studied for comparison between a probe and a gamma camera fitted with LEAP collimators. A different group of 25 patients (20 female and 5 male patients) were studied for comparison between LEAP and PH collimators. The patients were given 7.4-11 MBq (200-300 pCi) 123I capsules orally. Uptake with both the probe and the gamma camera was measured at 5 h and 24 h. The uptake measurements by these 3 methods were compared. RESULTS: Comparison of all the camera uptake values with the probe system correlated well with correlation coefficient values ranging from 0.912-0.988. The probe system yielded uptake ratios slightly higher than those measured by the gamma camera with LEAP collimator. Comparison between LEAP and PH uptake values resulted in a correlation coefficient of 0.979 for 5 h and 0.931 for 24 h uptake. CONCLUSION: Iodine-123 uptake with a gamma camera fitted with a LEAP collimator can accurately and consistantly be used to determine the thyroid uptake of 123I if proper ROIs are applied.     

Quantitation of myocardial iodine-123 MIBG uptake in SPET studies: a new approach using the left ventricular cavity and a blood sample as a reference

In patients with chronic heart failure increased sympathetic activity is related to unfavourable prognosis. Since myocardial iodine-123 metaiodobenzylguanidine ([¹²³I]MIBG) uptake is related to myocardial noradrenaline content, i.e. cardiac sympathetic activity, measurement of myocardial [¹²³I]MIBG uptake may be of clinical use in determining prognosis or the effect of pharmacological intervention in these patients. The aim of the present study was to evaluate a new method to quantitate myocardial [¹²³I]MIBG uptake with respect to reproducibility and accuracy. Eighteen [¹²³I]MIBG planar and single-photon emission tomography (SPET) studies of patients with chronic heart failure were evaluated. Myocardial uptake was calculated from the myocardial (MYO) to left ventricular cavity (C) count density ratio and the¹²³I activity in a blood sample. This was performed employing planar LAO images, a single-slice SPET method using the midventricular myocardial short-axis slice, and finally a multi-slice SPET method analysing semi-automatically drawn volumes of interest (VOIs). The accuracy of the multi-slice SPET method was verified using a cardiac phantom. The planar method was found to be reproducible [intra- and interobserver coefficients of variation (IACV and IRCV) were 0.025 and 0.012 respectively] but the mean MYO/C count density ratio was only 1.31±0.16 as a consequence of overprojection. For the single-slice SPET method IACV was 0.2 and IRCV was 0.13, representing poor reproducibility. For the multi-slice SPET method IACV was 0.051, IRCV was 0.047 and the mean MYO/C count density ratio was 5.4±2.42. Accuracy was 81% at a true MYO/C count density ratio of 6 in the phantom. It is concluded that the multi-slice SPET method using the left ventricular cavity VOI and a blood sample as a reference is a reproducible and accurate method for assessing myocardial [¹²³I]MIBG uptake.     

The assay of iodine-123.

Compounds labeled with 123I are becoming more common in scintillation imaging due to the convenient combination of the 13.3-hr half-life and the 159-keV gamma radiation. Here attention is drawn to the particularly large summing effects observed when 123I is counted in a well counter. These could lead to errors in the assay of doses if the analyzer windows used are too narrow.     

Influence of drugs on myocardial iodine-123 metaiodobenzylguanidine uptake in rabbit myocardium

About 15 years ago, iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging was introduced for the evaluation of myocardial sympathetic nerve function. Two uptake mechanisms for MIBG have so far been identified: uptake type I, a saturable, energy-dependent mechanism, and uptake type II, a non-saturable, energy-independent mechanism. We incubated isolated rabbit myocardial tissue samples with ¹²³I-MIBG in order to assess the uptake characteristics and the influence of varying incubation conditions. Furthermore, we examined the effects of several drugs and uptake inhibitors on the myocardial uptake of MIBG. The in vitro myocardial uptake of MIBG reached a steady plateau at 23.87%±3.63% after 1 h, i.e. a concentration gradient of 10, in a thermo-independent manner within a concentration range from 1.5 to 1500 μM. This indicates an unsaturable uptake process in the tested concentrations. Pre-incubation with the following drugs caused a significant inhibitory effect on myocardial MIBG uptake: haloperidol, levomepromazine, metoprolol, labetalol and clomipramine. According to our findings, the uptake mechanism seems to be an unspecific process, but the concentration gradient of 10 makes passive diffusion unlikely. Further studies with uptake-II-blocking substances as well as with isolated myocardial cells will be needed to clarify the nature of the myocardial MIBG uptake mechanism. Received 1 September and in revised form 18 November 1999     

Influence of drugs on myocardial iodine-123 metaiodobenzylguanidine uptake in rabbit myocardium

About 15 years ago, iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging was introduced for the evaluation of myocardial sympathetic nerve function. Two uptake mechanisms for MIBG have so far been identified: uptake type I, a saturable, energy-dependent mechanism, and uptake type II, a non-saturable, energy-independent mechanism. We incubated isolated rabbit myocardial tissue samples with 123I-MIBG in order to assess the uptake characteristics and the influence of varying incubation conditions. Furthermore, we examined the effects of several drugs and uptake inhibitors on the myocardial uptake of MIBG. The in vitro myocardial uptake of MIBG reached a steady plateau at 23.87%+/-3.63% after 1 h, i.e. a concentration gradient of 10, in a thermo-independent manner within a concentration range from 1.5 to 1500 microM. This indicates an unsaturable uptake process in the tested concentrations. Preincubation with the following drugs caused a significant inhibitory effect on myocardial MIBG uptake: haloperidol, levomepromazine, metoprolol, labetalol and clomipramine. According to our findings, the uptake mechanism seems to be an unspecific process, but the concentration gradient of 10 makes passive diffusion unlikely. Further studies with uptake-II-blocking substances as well as with isolated myocardial cells will be needed to clarify the nature of the myocardial MIBG uptake mechanism.     

Decreased iodine-123 IMP caudate nucleus uptake in patients with Huntington's disease

To determine whether I-123 isopropyl iodoamphetamine (IMP) uptake is reduced in the basal ganglia of patients with Huntington's disease compared with that in aged-matched normal and abnormal control subjects, a caudate ratio was defined that compared the average separation (in pixel units) between the midline and the left and right caudate heads to the width of the brain as measured on transaxial cross-sections of I-123 IMP SPECT brain images. For six patients with Huntington's disease, the average caudate ratio was 29.0% (SD +/- 2.7%), significantly higher than that for 12 normal volunteer subjects (average caudate ratio, 19.1% +/- 3.5%; p less than 0.001) and 13 patients with a variety of other neurologic disorders (average caudate ratio, 19.3 +/- 2.2%; p less than 0.001).     

Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123-IBZM.

We studied the uptake, distribution, metabolism and washout of the dopamine D2 receptor ligand [123I]IBZM in healthy subjects (n = 12) with dynamic brain SPECT. The highest radioactivity level was detected in the striatum. Operationally-defined striatal "specific" uptake peaked at 69 min postinjection of radioligand and showed a gradual decline of 15% per hour thereafter. "Specific" uptake at maximal counts represented 53% of the total striatal radioactivity. Two subjects received haloperidol (20 micrograms/kg i.v.) 80 min postinjection of radioligand. Haloperidol caused a 2.6-fold increase in the rate of washout of specific striatal activity in comparison to that in the 10 control subjects and was consistent with drug-induced displacement of radioligand from the dopamine D2 receptor. Two classes of metabolites were detected in plasma and urine: a polar fraction, not extracted by ethyl acetate, and a nonpolar, extractable fraction consisting of parent compound and two compounds having shorter retention times on reversed-phase HPLC. Greater than half the plasma parent was metabolized within 10-15 min after administration. The volume of distribution, estimated from the peak arterial plasma concentration at 50-75 sec, was 7.7-10.2 l; the free (nonprotein bound) fraction of [123I]IBZM after in vitro incubation with blood or plasma was 4.4% +/- 0.4%. These results suggest that [123I]IBZM exhibits uptake in brain regions with high D2 receptor density and shows a relatively stable washout during which drugs affecting dopaminergic transmission may be administered.     

Dual-isotope brain SPECT imaging with technetium-99m and iodine-123: validation by phantom studies.

Phantom studies were employed to determine whether the enhanced energy resolution (9.7% FWHM) of a new high-resolution, three-headed single-photon emission computed tomograph might permit the simultaneous acquisition of 99mTc and (123)I. Various window widths (15% and 10%) and positions (centered and asymmetric to the photopeak) were used to examine cross-contamination between these two isotopes. Brain phantom experiments using a 15% centered 99mTc window in conjunction with a 10% asymmetric (123)I window (upper half of the (123)I photopeak) demonstrated that approximately 95% of observed counts were derived from the isotope of interest. Shifting the (123)I window from asymmetric to centered resulted in a significant increase in contamination of the (123)I window. Shifting the 99mTc window from centered to asymmetric did not significantly alter image quality for 99mTc. Separate experiments employing vials with varying isotope concentrations demonstrated that quantitative recovery from mixed 99mTc and (123)I sources was equivalent to that from matched single-isotope sources (r2 > or = to 0.90).     

Uterine uptake of iodine-123 metaiodobenzylguanidine during the menstrual phase of uterine cycle

Radioiodinated I-123 metaiodobenzylguanidine (MIBG) has been used for diagnostic purposes for detection of apudomas. In this paper normal physiological uptake of I-123 MIBG by the uterus during the menstrual phase of the uterine cycle is reported. It is likely that I-123 MIBG can be used to evaluate some of the problems in this context.     

Cardiac iodine-123 metaiodobenzylguanidine uptake in animals with diabetes mellitus and/or hypertension

The aim of the present study was to evaluate the use of the noradrenaline analogue iodine-123 metaiodobenzylguanidine ([¹²³I]MIBG) for the assessment of cardiac sympathetic activity in the presence of diabetes mellitus and/or hypertension in animal models. One model used Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) rendered diabetic at 12 weeks of age by an intravenous injection of streptozotocin (STZ). The other model used lean and obese Zucker rats. In all groups basic haemodynamic values were established and animals received an intravenous injection of 50 Ci [¹²³I]MIBG. Initial myocardial uptake and washout rates of [¹²³I]MIBG were measured scintigraphically during 4 h. After sacrifice, plasma noradrenaline and left cardiac ventricular -adrenoceptor density was determined. The diabetic state, both in STZ-treated rats (direct induction) and in obese Zucker rats (genetic induction), appeared to induce a lower cardiac density of -adrenoceptors, indicative of increased sympathetic activity. Cardiac [¹²³I]MIBG then showed increased washouts, thereby confirming enhanced noradrenergic activity. This parallism of results led to the conclusion that [¹²³I]MIBG wash-out measurements could provide an excellent tool to assess cardiac sympathetic activity non-invasively. However, in hypertension (WKY vs SHR), both parameters failed to show parallelism: no changes in -adrenoceptor density were found, whereas [¹²³I]MIBG wash-out rate was increased. Thus, either [¹²³I]MIBG washout or ß-adrenoceptor density may not be a reliable parameter under all circumstances to detect changes in the release of noradrenaline. Changes in the initial uptake of [¹²³I]MIBG were observed as well. This may be a good marker for the disappearance of cardiac innervation, but it seems not to be a good parameter for distinguishing between loss of sympathetic innervation and enhanced uptake of noradrenaline in pathological conditions.     

Discordant iodine-123 metaiodobenzylguanidine uptake area reflects recovery time dispersion in acute myocardial infarction

lodine-123 metaiodobenzylguanidine (MIBG) uptake was reported to be reduced compared to Tl-201 (Tl) in acute myocardial infarction (AMI). Within such an area, degrees of both sympathetic neural function and ischemic myocardial cell damage are considered to be greatly dispersed. These kinds of damage were reported to effect reporalization time in myocardial cells, and we evaluated our hypothesis that extension of the discordant MIBG uptake area correlates with recovery time (RT) dispersion and relate ventricular arrhythmias in AMI. MIBG and Tl images were obtained in AMI patients. Regional Tl or MIBG uptake was estimated in 9 segments of SPECT by using four-point scoring. The total score was the sum of scores in 9 SPECT segments. ATI-MIBG was calculated by subtracting the total MIBG score from the total Tl score. Corrected RT (RTc) was measured as a signal-averaged ECG. RTc dispersion was defined as the difference between maximal and minimal RTc. The patients were assigned to two groups (group A; < or = Lown 4a, group B; > or = Lown 4b) according to the results of 24-hour Holter monitoring. A positive correlation between RTc dispersion and ATI-MIBG was found. ATI-MIBG and RTc dispersion in group B were greater than those in group A. These results suggested that ATI-MIBG could be used to predict the development of malignant ventricular arrhythmias.     

Dosimetry of iodine-123 iomazenil in humans

The distribution of the central benzodiazepine receptor specific ligand iodine-123 iomazenil was investigated in seven human adults from whole-body scans, blood samples and urine collected up to 24 h after injection. Using 12 source organs, the MIRD method was applied to calculate the absorbed radiation dose of the radioligand in various organs. The urinary bladder wall (0.15 mGy/MBq), lower large intestinal wall (0.071 mGy/MBq) testes (0.044 mGy/MBq) and upper large intestined wall (0.038 mGy/MBq) received the highest absorbed doses. The average effective dose equivalent of ¹²³I-IBZM for adults was estimated to be 0.033 mSv/MBq.     

Clinical deficits in Huntington disease correlate with reduced striatal uptake on iodine-123 epidepride single-photon emission tomography.

Huntington disease (HD) is characterized by severe abnormalities in neurotransmitter concentrations and neuroreceptor density. Quantitative changes in dopamine D(2) receptors occur in the early stages of HD and may be detectable with functional neuroimaging techniques. The aim of this study was to determine whether dopamine D(2) receptor imaging with single-photon emission tomography (SPET) identifies preclinical abnormalities in HD. The study population comprised 32 subjects from families affected by HD: 11 were genetically normal while 21 were genetically positive for HD (seven asymptomatic, six early, three moderate and five advanced findings). Disease severity was determined using a standardized quantitative neurological examination (QNE) and the mini-mental status examination (MMSE). Subjects underwent brain SPET imaging 120 min following intravenous injection of iodine-123 epidepride. Ratios of target (striatal) to nontarget (occipital or whole-brain) uptake were calculated from the reconstructed image data. Striatum to occiput and striatum to whole-brain count ratios correlated negatively with disease stage (P=0.002 and P=0.0002) and QNE (P<0. 002 and P=0.0002), and positively with the MMSE (P=0.001 and P<0. 001). Uptake was significantly reduced in the moderate-advanced subjects but was still normal for the asymptomatic and early symptomatic stages. It is concluded that reductions in striatal dopamine D(2) receptor density can be detected with (123)I epidepride at moderate or advanced stages of HD. In contrast to other reports, we could not identify abnormalities in clinically unaffected or early stages of HD.     

Pharmacokinetics and dosimetry of iodine-123 labelled PE2I in humans, a radioligand for dopamine transporter imaging

The iodine-123 labelled selective ligand N-(3-iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4-methylphenyl)nortropane ([¹²³I]PE2I) was evaluated as a probe for in vivo dopamine transporter imaging in the human brain. Six healthy subjects were imaged with a high-resolution single-photon emission tomography scanner. Striatal radioactivity peaked at 1 h after injection. The background radioactivity was low. The volume of distribution in the striatum was 94±24 ml/ml. The results were compared with those of [¹²³I]β-CIT imaging. There was no significant uptake of [¹²³I]PE2I in serotonin-rich regions such as the midbrain, hypothalamus and anterior gingulus, suggesting that in vivo binding is specific for the dopamine transporter. One main polar metabolite of [¹²³I]PE2I was found in plasma, and the parent plasma concentration decayed rapidly. Radiation exposure to the study subject is 0.022±0.004 mSv/MBq (effective dose). The preliminary results suggest that [¹²³I]PE2I is a selective SPET ligand for imaging striatal dopamine transporter density. Received 9 December 1997 and in revised form 20 February 1998