A scintigraphic comparison of iodine-123-metaiodobenzylguanidine and an iodine-labeled somatostatin analog (Tyr-3-octreotide) in metastatic carcinoid tumors.

A number of neoplasms are known to express somatostatin receptors, and the use of somatostatin receptor imaging in their localization has recently been described. We compared an 123I-labeled somatostatin analog Tyr-3-octreotide (TOCT) and 123I-labeled metaiodobenzylguanidine (MIBG) scintigraphy in seven patients with histologically proven metastatic carcinoid tumors. The optimum time for identifying tumor uptake on scanning after [123I]MIBG was 24-48 hr, and after 123I-TOCT 10-30 min postinjection. Both radiopharmaceuticals showed a varying spectrum of tracer uptake ([123I]MIBG showed no uptake in one patient; minimal in two; moderate in two; and intense in two; 123I-TOCT showed no uptake in two patients; minimal uptake in one; moderate uptake in two; and intense uptake in two). In two patients, 123I-TOCT identified metastatic lesions not seen by [123I]MIBG scintigraphy. These preliminary results suggest that [123I]MIBG and 123I-TOCT are useful and complementary imaging techniques for detecting metastatic carcinoid tumors.     

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.     

Iodine-123-metaiodobenzylguanidine scintigraphy in patients with chemodectomas of the head and neck region

While studying the uptake of iodine-123-metaiodobenzylguanidine ([123I]MIBG) in chemodectomas, we coincidentally detected catecholamine secreting tumors in 5 out of 14 patients. In three of these cases, a norepinephrine secreting abdominal paraganglioma was subsequently removed. One patient had a norepinephrine secreting chemodectoma and one had a dopamine secreting chemodectoma. Prior to [123I]MIBG imaging and urinary catecholamine measurements, endocrine activity was suspected in only one of these five patients. Apart from these five cases, two other patients showed elevated catecholamine secretion and abnormal abdominal [123I]MIBG concentrations. However, these two patients were not surgically explored, because of normal computed tomography (CT) and magnetic resonance (MRI) studies. We suspect that catecholamine-secreting tumors are more common in patients with chemodectomas than is assumed in the literature, and we therefore recommend urinary catecholamine screening for all patients with chemodectomas. In case of elevated catecholamine secretion, MIBG scintigraphy is indicated.     

Quantitative study of radioiodinated metaiodobenzylguanidine uptake in children with neuroblastoma: correlation with tumor histopathology

Six children with neuroblastoma and one with ganglioneuroma received [125I] metaiodobenzylguanidine (MIBG) before major surgery. Uptake of [125I]MIBG in the excised tissues was measured by scintillation counting, and the material was submitted for histopathology. The ranges of uptake of [125I]MIBG, expressed as percent of the injected dose per gram of tissue, were as follows: for neuroblastoma 0.0013-0.071, for ganglioneuroma 0.0017-0.0028, and for non-neoplastic control tissues 0.0002-0.011. The quantitative uptake of [125I]MIBG by neuroblastoma varied between different patients and between different parts of individual tumors. The more undifferentiated tumors took up more [125I]MIBG and may be more likely to respond to targeted radiotherapy with MIBG.     

Metaiodobenzylguanidine to map scintigraphically the adrenergic nervous system in man

Metaiodobenzylguanidine (MIBG) localizes in adrenergic neurons; MIBG labeled with 123I then serves as an analog of norepinephrine, and concentrations of [123I]MIBG reflect sites of adrenergic neurons in organs. Movements of [123I]MIBG into and out of organs were measured by quantitative scintigraphy in man. We perturbed adrenergic neuron function in several ways, and [123I]MIBG concentrations in the heart were subsequently altered in patterns consistent with the concept that [123I]MIBG resides mostly in adrenergic neurons. Uptake of [123I]MIBG into the heart was inhibited by the tricyclic drug, imipramine, and this agent also accelerated the rate of loss of [123I]MIBG. Phenylpropanolamine, a sympathomimetic drug that acts by displacing norepinephrine from neurons, increased the rates of loss of [123I]MIBG from the heart. Exercise was followed by a movement of [123I]MIBG into blood and urine. Generalized autonomic neuropathies were associated with marked diminutions of [123I]MIBG uptake into the heart. We conclude that quantitative scintigraphy in patients will enable determinations of regional disturbances in integrity (by measuring uptake of [123I]MIBG) and function (by measuring rates of loss of [123I]MIBG) of the adrenergic nervous system in the heart.     

Imaging of carcinoid tumors with iodine-123 metaiodobenzylguanidine

Scintigraphy with 123I-radiolabeled metaiodobenzylguanidine (MIBG) was performed successfully in two patients with metastatic carcinoid tumor. The scintigraphic findings show diversity of the tumor deposits in the uptake of [123I]MIBG in the same patient and between patients.     

Iodine-123-4-amino-3-iodobenzylguanidine, a new sympathoadrenal imaging agent: comparison with iodine-123 metaiodobenzylguanidine

Iodine-123-4-amino-3-iodobenzylguanidine ([123I]AIBG), an analog of 123I metaiodobenzylguanidine ([123I]MIBG), has an advantage in having a more rapid and simple synthesis. This, combined with animal data that suggested a greater affinity of the new radiopharmaceutical for the autonomic innervation of the myocardium led us to study the biodistribution of [123I]AIBG in three men with metastatic pheochromocytoma. In all instances, [123I]AIBG revealed the same metastatic deposits shown by [123I]MIBG. Iodine-123 AIBG uptake, however, was greater than [123I]MIBG in lung, gut, and spleen. These higher backgrounds may pose diagnostic problems in some cases.     

Interaction of metaiodobenzylguanidine with cardioactive drugs: an in vitro study

Metaiodobenzylguanidine (MIBG), an analogue of noradrenaline, is used to explore the functional integrity of sympathetic nerve endings in the human heart. Various drugs inhibit noradrenaline transport systems and may block the uptake of MIBG. As in vivo studies of the effect of these drugs on myocardial [¹²³I]MIBG uptake are often difficult to perform, we used an in vitro human blood platelet model for this purpose. A platelet preparation from healthy volunteers was incubated with [¹²⁵I]MIBG alone or different concentrations of drugs currently used in cardiology. Labetalol and propranolol inhibited [¹²⁵I]MIBG uptake, whereas all other drugs tested (other -blockers, calcium inhibitors, digoxin and amiodarone) had no effect even at doses exceeding 50 M. The labetalol dose inhibiting 50% of [¹²⁵I]MIBG uptake was lower than the plasma concentration of this drug in treated patients, whereas the propranolol dose was higher. This in vitro study of the effect of drugs on MIBG uptake by human blood platelets is predictive of their in vivo effect on myocardial uptake of [¹²³I]MIBG in treated patients, provided that plasma concentration is taken into account.     

Optimizing MIBG therapy of neuroendocrine tumors: preclinical evidence of dose maximization and synergy

[(131)I]meta-Iodobenzylguanidine ([(131)I]MIBG) has been used for the therapy of tumors of neuroectodermal origin since the 1980s. Its role in the management of these malignancies remains controversial because of the large variation in response rates. Appreciation of the mode of conveyance of [(131)I]MIBG via the noradrenaline transporter into malignant cells and of factors that influence the activity of the uptake mechanism has indicated various ways in which the effectiveness of this type of targeted radiotherapy may be improved. Experimental observations indicate that radiolabeling of MIBG to high specific activity reduced the amount of cold competitor, thereby increasing tumor dose and minimizing pressor effects. We observed supra-additive tumor cell kill and inhibition of tumor growth following combined topotecan and [(131)I]MIBG treatment. The improved efficacy is related to topotecan's increased disruption of DNA repair. Radiation damage to targeted tumors may also be enhanced by the use of the alpha-particle emitter [(211)At]astatine rather than (131)I as radiolabel. Furthermore, recent experimental findings indicate that [(123)I]MIBG may have therapeutic potential over and above its utility as an imaging agent. It has recently been demonstrated that potent cytotoxic bystander effects were induced by the intracellular concentration of [(131)I]MIBG, [(123)I]MIBG or meta-[(211)At]astatobenzylguanidine. Identification of the nature of bystander factors could be exploited to maximize the specificity and potency of MIBG-targeted radiotherapy. By employing a range of strategies, there are good prospects for the improvement of the [(131)I]MIBG therapy of neuroectodermal tumors.     

Iodine-131 metaiodobenzylguanidine intra- and extravesicular accumulation in the rat heart

In order to establish the appropriate time for [123I]MIBG human myocardial imaging to assess the adrenergic nerve activity, the time courses of metaiodobenzylguanidine (MIBG) intra- and extravesicular accumulation in the rat heart were estimated by using [131I]MIBG and reserpine. In the heart, the intravesicular accumulation was relatively constant, while the extravesicular accumulation decreased rapidly from 5 min to 6 hr. The intravesicular percentage of the total cardiac tissue concentration reached a plateau value of 50% at 4 hr after i.v. injection of [131I]MIBG. In the spleen, similar time courses were observed as those in the heart, both of these organs being richly innervated by adrenergic nerves. Along with the time activity difference previously observed in the human hearts, these results suggest that at 4 hr post i.v. injection, [123I]MIBG myocardial imaging will best express the neuronal accumulation of the tracer and may be useful for the assessment of adrenergic function in various pathological conditions of the human heart.     

Iodine-123 metaiodobenzylguanidine imaging of the heart in idiopathic congestive cardiomyopathy and cardiac transplants

Iodine-123 metaiodobenzylguanidine ([123I]MIBG) is a norepinephrine analog which can be used to image the sympathetic innervation of the heart. In this study, cardiac imaging with [123I]MIBG was performed in patients with idiopathic congestive cardiomyopathy and compared to normal controls. Initial uptake, half-time of tracer within the heart, and heart to lung ratios were all significantly reduced in patients compared to normals. Uptake in lungs, liver, salivary glands, and spleen was similar in controls and patients with cardiomyopathy indicating that decreased MIBG uptake was not a generalized abnormality in these patients. Iodine-123 MIBG imaging was also performed in cardiac transplant patients to determine cardiac nonneuronal uptake. Uptake in transplants was less than 10% of normals in the first 2 hr and nearly undetectable after 16 hr. The decreased uptake of MIBG suggests cardiac sympathetic nerve dysfunction while the rapid washout of MIBG from the heart suggests increased cardiac sympathetic nerve activity in idiopathic congestive cardiomyopathy.     

Norepinephrine transporter density as a causative factor in alterations in MIBG myocardial uptake in NIDDM model rats

Cardiac scintigraphic studies with iodine-123 labeled metaiodobenzylguanidine ([(123)I]MIBG) have demonstrated global and regionally pronounced decreases in myocardial accumulation of radioactivity in diabetes. The aim of this study was to investigate the cause of the regional differential decrease in accumulation. To this end, we investigated the global and regional myocardial distribution of [(125)I]MIBG in GK/Crj (GK) rats [a model of non-insulin-dependent diabetes mellitus (NIDDM)] and assessed the responsibility of regional myocardial blood flow, myocardial and plasma norepinephrine (NE) content, and norepinephrine transporter (NET) function for the regional variations in [(125)I]MIBG accumulation. To investigate the responsibility of myocardial blood flow for the alterations in MIBG accumulation, dual-isotope autoradiographic studies with [(125)I]MIBG and technetium-99m hexakis-2-methoxy-2-isobutylisonitrile (MIBI), a tracer for the measurement of myocardial blood flow, were carried out in GK rats and control rats. The results in respect of the uptake of radioactivity into various myocardial regions were expressed as distribution absorption ratios [DAR = (radioactivity of tissue/g of tissue) x (body weight/total injected dose)]. In control rats, uptake of [(125)I]MIBG was significantly higher in the inferior wall than in the anterior wall (anterior wall, 6.35 +/- 0.90; inferior wall, 8.12 +/- 1.27: P < 0.001). On the other hand, in GK rats, uptake of [(125)I]MIBG was similar between the anterior wall and the inferior wall (anterior wall, 4.91 +/- 0.71; inferior wall, 4.81 +/- 0.69). Compared with control rats, uptake of [(125)I]MIBG in GK rats was decreased in both the anterior wall and the inferior wall. Uptake of (99m)Tc-MIBI was not significantly different between the anterior and inferior walls in control (anterior wall, 17.9 +/- 4.42; inferior wall, 18.1 +/- 4.52) and GK rats (anterior wall, 16.6 +/-8.03; inferior wall, 16.7 +/- 7.90), indicating that myocardial blood flow did not change regionally in either control or GK rats, and that the blood flow was not responsible for the differential decrease in MIBG accumulation in GK rats. Cardiac and plasma NE levels were measured using an HPLC-electrochemical detection system. The cardiac and plasma NE concentrations were not significantly different between control (anterior wall, 347 +/- 56 ng/g; inferior wall, 354 +/- 31 ng/g; plasma 9.38 +/- 2.10 ng/ml) and GK rats (anterior wall, 323 +/- 62 ng/g; inferior wall, 344 +/- 35 ng/g; plasma, 9.41 +/- 2.39 ng/ml). The density and affinity of NET were investigated by studying the binding of [(3)H]desipramine to cardiac membranes. The B(max) (fmol/mg protein) in the inferior wall was significantly higher than that in the anterior wall in the control rats (anterior wall, 364 +/- 28; inferior wall, 459 +/- 36: P < 0.05). On the other hand, there was no significant difference in the B(max) value between the anterior and inferior walls in GK rats (anterior wall, 263 +/- 42; inferior wall, 251 +/- 27). In conclusion, myocardial MIBG uptake was differentially reduced in GK rats, and this decrease was associated with a decrease in NET density, but the regional myocardial blood flow and the NE concentration were not responsible for the alterations in MIBG uptake. Thus, NET density was identified as the factor responsible for decreases in MIBG accumulation.     

SPECT studies of brain tumors with L-3-[123I] iodo-alpha-methyl tyrosine: comparison with PET, 124IMT and first clinical results

L-3-[123I]iodo-alpha-methyltyrosine (123IMT) like tyrosine has been reported previously to have a high affinity for a transport system in the blood-brain-barrier (BBB). We examined the kinetic behavior of 124IMT in brain and plasma in two patients with glioblastoma using dynamic positron emission tomography (PET). 124IMT accumulated in brain and tumor tissue, reaching a maximum after 15 min, with a washout of 20% to 35% at 60 min postinjection. Animal experiments confirmed the accumulation of the intact tracer in murine brain, but there was no incorporation into proteins. SPECT studies with 123IMT in patients with different types of brain tumors showed increased uptake in 26 of 32 tumors. Although nonspecific uptake in tumors must be considered, the accumulation of IMT in normal brain and in some tumors with intact BBB suggests a specific uptake of IMT. As transport is the main determinant of initial amino acid uptake, 123IMT appears to be a suitable SPECT tracer of amino acid uptake although it is not incorporated into protein.     

In vivo evaluation in mice and metabolism in blood of human volunteers of [123I]iodo-PK11195: a possible single-photon emission tomography tracer for visualization of inflammation

We report the in vivo evaluation (biodistribution, displacement and metabolization in blood, brain and heart) in mice and the metabolism in blood of human volunteers of iodine-123 labelled 1-(2-iodophenyl)-N-methyl-N-(1-methyl-propyl)-3-isoquinoline carboxamide ([123I]iodo-PK11195), a potential radioligand for visualization of inflammation in humans by single-photon emission tomography. In three series of 18 white mice (NMRI, 20-25 g), the concentration of radioactivity was measured during 48 h. Blood samples were taken, organs and intestines were excised, excretion was collected and all tissues were weighed and counted for radioactivity. The tissue uptake of radioactivity was measured as % of the injected activity/g of tissue. The excretion was expressed as % of the injected activity. Selective tissue uptake was investigated by pretreatment of another three series of 18 mice with cold PK11195 (1 mg/kg body weight). There was an inflow of [123I]iodo-PK11195 in the brain and among peripheral organs, heart (42.3%), lungs (133.5%) and kidneys (18.4%) had the highest uptake. After pretreatment with cold PK11195, there was a decrease in accumulation in the latter three organs, especially in heart (ca. 55%) and lungs (ca. 80%). Metabolite analysis was performed using high-performance liquid chromatography (HPLC). First, the extraction yield of [123I]iodo-PK11195 from blood and tissue was assessed, and found to be >90%. From blank blood samples and organs spiked with [123I]iodo-PK11195 it was concluded that no metabolization took place during the extraction procedure. Analysis of plasma, brain and heart of mice showed that 10 min p.i. [123I]iodo-PK11195 was the only significant (ca. 95%) radioactive compound in brain and heart where-as in plasma other radioactive products (>60%) appeared. Analysis of plasma samples of the three human volunteers at 7, 20, 37 and 50 min p.i. showed that [123I]iodo-PK11195 rapidly decomposes into two polar metabolites, which at these time points accounted for, respectively 31%, 62%, 75% and 77% of the total activity.     

Radioiodinated metaiodobenzylguanidine (MIBG): radiochemistry, biology, and pharmacology

As an analogue of adrenergic neurotransmitter norepinephrine (NE), metaiodobenzylguanidine (MIBG) demonstrates high uptake both in normal sympathetically innervated tissues, such as the heart and salivary glands, and in tumors that express the NE transporter (NET), specifically those of neural crest and neuroendocrine origin. In 1994, (131)I-MIBG, also known as iobenguane I-131 intravenous, received Food and Drug Administration (FDA) approval as an imaging agent. In 2008, (123)I-MIBG was also approved by FDA as a tumor imaging agent. Commercial formulations of radioiodinated MIBG are prepared on the basis of radioiodide exchange reaction with unlabeled MIBG as a precursor and contain large mass amounts of unlabeled MIBG, or "cold carrier," molecules. Because the cold MIBG molecules competitively inhibit the uptake of radiolabeled MIBG molecules by adrenergic and neuroendocrine cells expressing NET, no-carrier-added (n.c.a.), high specific activity (SA) radioiodinated MIBG preparations have been developed on the basis of electrophilic radioiodination reaction and solid-phase technology by using dibutylstanyl benzylguanidine precursor linked to polymers. On the basis of n.c.a. synthetic procedures, therapeutic doses of [(131)I]MIBG can be administered with very high SA (1600 mCi/μmol or 5734 mCi/mg). The very high SA of n.c.a. [(131)I]MIBG drug would increase the specific cellular uptake of adrenergic neurons and neuroendocrine tumor cells expressing NET.     

Iodine-131 MIBG scintigraphy of neuroendocrine tumors other than pheochromocytoma and neuroblastoma

Metaiodobenzylguanidine (MIBG) locates most pheochromocytomas and neuroblastomas. The tracer is concentrated in intracellular storage vesicles by an active process. Many other neuroendocrine tumors of the amine precursor uptake and decarboxylation (APUD) series have hormonal storage vesicles and, thus, the potential to take up [131I]MIBG. A variety of neuroendocrine tumors in 57 patients were studied 1, 2, and 3 days after 0.5 mCi [131I]MIBG. Views from skull to pelvis were obtained. Results of MIBG scans were compared with all available imaging modalities (including plain radiography, liver scan, ultrasound, computed tomography, and angiography) and surgical exploration. The neuroendocrine nature of the tumor was determined by histology, immunohistochemistry, electron microscopy, and the assay of appropriate biogenic amines and peptide hormones. Results were (positive/total cases): carcinoids (four of ten), nonsecreting paragangliomas (three of three), sporadic medullary carcinomas of the thyroid (MCT) (one of five), familial MCT (one of 26), chemodectomas (two of five), oat cell carcinomas (zero of four), choriocarcinoma (one of one), atypical schwannoma (with storage granules) (one of one), Merkel cell skin cancer (one of one), islet cell carcinoma (zero of one). We conclude that a wide range of neuroendocrine tumors show [131I]MIBG uptake; tumors other than pheochromocytomas and neuroblastomas are less often seen scintigraphically, but in certain cases (e.g., carcinoid and nonsecreting paragangliomas) scintigraphy may be useful in depicting the extent and location of disease and may indicate therapeutic potential. Iodine-131 MIBG shows promise in the diagnosis and staging of tumors of varied types.     

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.     

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.     

Renal accumulation and excretion of radioiodinated 3-iodo-α-methyl-<Emphasis Type="SmallCaps">L</Emphasis>-ty rosine

OBJECTIVE: We investigated mechanisms of renal accumulation of radioiodinated 3-iodo-alpha-methyl-L-tyrosine (IMT), which has been used clinically for tumor imaging and as an amino acid transport marker in studies of brain and pancreas function. METHODS: In this study, we used 125I- or 123I-labeled IMT ([125I]IMT or [123I]IMT) as the transport marker. Partition coefficients of [125I]IMT were determined for hypothetic urine at pH ranging from 5 to 8. The examination of uptake and inhibition of [125I]IMT was performed using normal human renal proximal tubule epithelial cells (RPTEC), which are characteristic of the proximal convoluted tubule. The plasma protein binding ratio of [125I]IMT was determined using rats. In the in vivo experiments using mice, we examined biodistribution and excretion inhibition, and performed whole body autoradiography. Also, renal SPECT using [123I]IMT was performed using a normal canine. RESULTS: Very low lipophilicity of [125I]IMT in hypothetic urine suggests that a carrier-mediated pathway contributes to its marked kidney accumulation. [125I]IMT uptake into RPTEC was significantly inhibited by 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid (BCH) in a sodium-dependent manner, suggesting reabsorption mainly via system B0 in apical membrane of proximal tubule. Plasma protein binding ratio of IMT was 45.4 +/- 5.6%. At 6 hr after administration of IMT to mice, excretion via urinary tract was 77.51% of injected dose, and excretion into feces was 0.25%. Furosemide, ethacrynic acid and probenecid inhibited tubular secretion of [125I]IMT in mice. We obtained very clear autoradiographs of mouse renal cortex and a canine renal SPECT image (S2-like region). CONCLUSIONS: We believe that [123I]IM-T is useful for kidney imaging. In future studies, we plan to examine the use of [123I]IMT in diagnosis of disease.     

Clinical evaluation of no-carrier-added meta-[123I]iodobenzylguanidine for myocardial scintigraphy

In clinical and research studies, images obtained using carrier-added meta-[123I]iodobenzylguanidine (c.a. [123I]MIBG) have shown quite variable quality, with varying levels of uptake in lung, liver and mediastinum; this is a significant problem for quantification of the myocardial uptake by means of region ratios. First experimental and preliminary human data in respect of no-carrier-added (n.c.a.) [123I]MIBG are indicative of improved imaging quality. The aim of the present study was to evaluate the clinical value of myocardial scintigraphy with n.c.a. [123I]MIBG in patients with tachyarrhythmias. The study population comprised 24 patients with tachyarrhythmogenic diseases routinely studied by cardiac single-photon emission tomography (SPET) with [123I]MIBG. Twelve of the 24 patients were studied with c.a. [123I]MIBG (seven females and five males; mean age 42+/-13 years, range 20-60 years), whereas the other 12 were studied with n.c.a. [123I]MIBG (ten females, two males; mean age 41+/-11 years, range 18-60 years, P=NS). For quantification of the specific uptake in the different organs, count ratios were calculated on SPET images acquired 4 h p.i. Visual analysis of all [123I]MIBG scans showed improved image quality (improved contrast between heart and neighbouring organs) in n.c.a. studies as compared with c.a. studies. A significantly higher heart/left atrial blood ratio was found in the n.c.a. studies as compared with the c.a. studies (10.3+/-3.2 vs 5.3+/-1.3, P=0.0003); furthermore, significantly higher heart/lung and heart/liver ratios (2.5+/-0.6 vs 1.5+/-0.3, P=0.0002, and 0.8+/-0.2 vs 0.6+/-0.1, P=0.0006, respectively) were obtained in the c.a. studies, whereas lung/left atrial blood and liver/left atrial blood ratios showed no significant differences (4.2+/-1.3 vs 3.6+/-1.1, P=0.39, and 13.7+/-5.2 vs 9.6+/-2.2, P=0.21, respectively). In conclusion, the use of n.c.a. [123I]MIBG yields a significantly higher myocardial uptake associated with improvement in contrast between the heart and neighbouring organs and is therefore superior to the commercially available c.a. [123I]MIBG for use in clinical and research studies of the myocardial presynaptic sympathetic nervous system. Furthermore, our data indicate that for quantification the use of a left atrial blood reference region of interest, which is only available on SPET studies, is to be recommended.