High uptake of L-3-[123I]iodo-alpha-methyl tyrosine in pilocytic astrocytomas

Despite a favourable prognosis, pilocytic astrocytomas may exhibit signs of malignancy on various neuroimaging modalities. This retrospective analysis was conducted to determine whether scintigraphic features of malignancy are also found on single-photon emission tomography (SPET) using L-3-[123I]iodo-alpha-methyl tyrosine (IMT) as a tracer. Twenty patients with pilocytic astrocytomas were retrospectively selected from a large series of patients referred for the evaluation of primary or recurrent brain tumours. IMT SPET was performed in 16 patients, positron emission tomography (PET) using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) was available in 10 of the patients and SPET using technetium-99m tetrofosmin or thallium-201 had been performed in 11. Image analysis was performed using standard protocols to determine how many patients exceeded the respective thresholds of malignancy. Features of malignancy were found in 7/16 IMT SPET studies, in 7/10 FDG PET studies and in 7/11 of the residual SPET investigations. A significant correlation of tumour size and IMT uptake in primary pilocytic astrocytomas indicated partial volume effects to partly account for the differential uptake behaviour (n = 10, r = 0.87, P < 0.05). Differences in IMT uptake in primaries (1.7 +/- 0.6, n = 10) and in recurrent tumours (2.3 +/- 0.7, n = 6) did not attain statistical significance. IMT SPET results indicative of malignancy are regularly found in pilocytic astrocytomas, despite their good prognosis. No uptake may be detected in largely cystic or in small tumours.     

Diagnosis of recurrent head and neck squamous cell carcinoma with 3-[123I]iodo-L-alpha-methyltyrosine SPET

The distribution of 3-[123I]iodo-L-alpha-methyltyrosine (123I-3-IMT) in the tumour region of 21 patients with clinically suspected recurrent squamous cell head and neck carcinoma was studied. Single-photon emission tomography (SPET) imaging of the head and neck region was performed 10 min after the injection of 130-170 MBq 123I-3-IMT using a dual-detector gamma camera. Images were interpreted visually and classified as positive or negative for recurrent disease. In addition, target to background ratios (T/B) were measured using semi-automated region of interest analysis. IMT-SPET results were compared with the data derived from clinicopathological follow-up. IMT-SPET detected recurrent disease in 14 of 15 patients (sensitivity 93%). T/B ratios ranged between 1.5 and 2.4 (mean 1.88). One patient with a small tumour (1.2 cm) had a false-negative result. This is attributed to the limited spatial resolution of the SPET system. Five of six patients were correctly diagnosed to be negative for tumour recurrence. T/B ratios ranged between 1.2 and 1.4 (mean 1.30). In one patient IMT-SPET was positive without evidence of recurrence based on clinicopathological follow up. This finding was probably due to uptake into inflammatory tissue. IMT-SPET appears to be a sensitive tool (93%) for the detection of recurrent head and neck squamous cell carcinoma. Further studies with 123I-3-IMT as a metabolic tracer for the detection of head and neck cancer recurrence using SPET are recommended.     

Diagnosis of recurrent head and neck squamous cell carcinoma with 3-[123I]iodo-L-α-methyltyrosine SPET

The distribution of 3-[¹²³I]iodo-L-!-methyltyrosine (¹²³I-3-IMT) in the tumour region of 21 patients with clinically suspected recurrent squamous cell head and neck carcinoma was studied. Single-photon emission tomography (SPET) imaging of the head and neck region was performed 10 min after the injection of 130-170 MBq ¹²³I-3-IMT using a dual-detector gamma camera. Images were interpreted visually and classified as positive or negative for recurrent disease. In addition, target to background ratios (T/B) were measured using semi-automated region of interest analysis. IMT-SPET results were compared with the data derived from clinicopathological follow-up. IMT-SPET detected recurrent disease in 14 of 15 patients (sensitivity 93%). T/B ratios ranged between 1.5 and 2.4 (mean 1.88). One patient with a small tumour (1.2 cm) had a false-negative result. This is attributed to the limited spatial resolution of the SPET system. Five of six patients were correctly diagnosed to be negative for tumour recurrence. T/B ratios ranged between 1.2 and 1.4 (mean 1.30). In one patient IMT-SPET was positive without evidence of recurrence based on clinicopathological follow up. This finding was probably due to uptake into inflammatory tissue. IMT-SPET appears to be a sensitive tool (93%) for the detection of recurrent head and neck squamous cell carcinoma. Further studies with ¹²³I-3-IMT as a metabolic tracer for the detection of head and neck cancer recurrence using SPET are recommended.     

Parathyroid scintigraphy with 99mTc-MIBI and 123I subtraction: a comparison with magnetic resonance imaging and ultrasonography

The aim of this study was to evaluate the efficacy of 99mTc-MIBI and 123I subtraction scintigraphy for the detection of abnormal parathyroid glands to be referred for surgical treatment. Thirty-nine consecutive patients, including 35 primary and four secondary cases of hyperparathyroidism, were evaluated. 99mTc-MIBI/123I subtraction scintigraphy (MIBI/I) was performed on all patients, and the results were compared with delayed images of 99mTc-MIBI (D-MIBI), magnetic resonance imaging (MRI) and ultrasonography (US). The overall sensitivity of MIBI/I, MRI, US and D-MIBI was 55.9%, 43.4%, 50.8% and 39.0%, respectively. In cases of single-gland disease, the sensitivity of MIBI/I, MRI, US and D-MIBI was 62.1%, 48.3%, 55.2% and 44.8%, respectively. In cases of multi-gland disease, the sensitivity of MIBI/I, MRI, US and D-MIBI was 50.0%, 37.5%, 46.7% and 36.7%, respectively. In cases of parathyroid adenoma, the sensitivity of MIBI/I, MRI, US and D-MIBI was 71.4%, 50.0%, 71.4% and 50.0%, respectively. In cases of parathyroid hyperplasia, the sensitivity of MIBI/I, MRI, US and D-MIBI was 55.2%, 42.3%, 50.0% and 39.7%, respectively. It is concluded that 99mTc-MIBI/123I subtraction is more useful than the delayed imaging of 99mTc-MIBI, MRI and US.     

Transport mechanisms of 3-[123I]iodo-alpha-methyl-L-tyrosine in a human glioma cell line: comparison with [3H]methyl]-L-methionine.

The amino acid analog 3-[(123)I]iodo-alpha-methyl-L-tyrosine (IMT) is under clinical evaluation as a SPECT tracer of amino acid transport in brain tumors. This study investigated the carrier systems involved in IMT transport in human glioma cells in comparison with [3H-methyl]-L-methionine (3H-MET). METHODS: Human glioma cells, type 86HG-39, were cultured and incubated for 1 min at 37 degrees C with IMT and 3H-MET in the lag phase (1.2 d after seeding), exponential growth phase (3 d after seeding), and plateau phase (8 d after seeding). Experiments were performed in the presence and absence of Na+, during inhibition of system L amino acid transport by 2-aminobicyclo[2.2.1 ]heptane-2-carboxylic acid (BCH), and during inhibition of system A amino acid transport by 2-(methylamino)-isobutyric acid (MeAIB). RESULTS: IMT and 3H-MET uptake decreased by 55%-73% when the cells entered from the exponential growth phase into the plateau phase (P< 0.05; n = 3-11). Inhibition by BCH reduced uptake of IMT in the lag phase, exponential growth phase, and plateau phase by 90%-98% (P < 0.001; n = 3-6) and the uptake of 3H-MET by 73%-83% (P < 0.001; n = 3-11). In a Na+-free medium 3H-MET uptake was reduced by 23%-33% (P < 0.05; n = 3-11), whereas IMT uptake was not significantly different. MeAIB showed no significant effect on IMT or 3H-MET uptake in either phase. CONCLUSION: Transport of both IMT and 3H-MET depends on the proliferation rate of human glioma cells in vitro and is dominated by BCH-sensitive transport. These data indicate that system L is induced in rapidly proliferating glioma cells and is the main contributor to the uptake of both tracers. 3H-MET transport showed a minor Na+ dependency that was not attributable to system A. The similarity of transport mechanisms of both tracers emphasizes the clinical equivalence of IMT SPECT and (11)C-MET PET for the diagnostic evaluation of gliomas.     

Comparative biodistribution study of the new tumor tracer [123I]-2-iodo-L-phenylalanine with [123I]-2-iodo-L-tyrosine

INTRODUCTION: Both A- and l-type amino acid transport are increased in tumor cells relative to normal tissue; these transport systems have been the major focus of the development of amino acid tumor tracers to overcome the limitations of [(18)F]-fluorodeoxyglucose ((18)F-FDG). The newly developed tracer 2-amino-3-(2-[(123)I]iodophenyl)propanoic acid ([(123)I]-2-iodo-l-phenylalanine) showed high and specific tumor uptake, slow renal elimination and low brain uptake. We compared [(123)I]-2-iodo-L-phenylalanine with 2-amino-3-(4-hydroxy-2-[(123)I]iodophenyl)propanoic acid ([(123)I]-2-iodo-L-tyrosine), an L-tyrosine analogue that has recently entered clinical trials. METHODS: [(123)I]-2-iodo-L-phenylalanine and [(123)I]-2-iodo-L-tyrosine were evaluated in rhabdomyosarcoma tumor-bearing athymic mice by means of dynamic planar imaging (DPI) and dissection. A displacement study with L-phenylalanine was performed to prove the specificity of tracer tumor uptake, and kinetic modeling was applied to the DPI results. Moreover, the biodistribution of both tracers was compared with that of (18)F-FDG. RESULTS: Both [(123)I]-2-iodo-L-phenylalanine and [(123)I]-2-iodo-L-tyrosine showed fast, high and specific tumor accumulation with no significant difference. However, [(123)I]-2-iodo-L-phenylalanine was cleared faster from the blood to the bladder in comparison with the tyrosine analogue. Moreover, [(123)I]-2-iodo-L-phenylalanine tumor uptake equilibrated faster with blood. Dissection showed that [(123)I]-2-iodo-L-tyrosine slightly accumulated in the liver, which was not the case for the phenylalanine analogue. In contrast to (18)F-FDG, both tracers showed low uptake in the heart and normal brain tissue, which is advantageous for tumor detection in these organs. CONCLUSIONS: [(123)I]-2-iodo-L-phenylalanine showed more promising characteristics for oncological imaging as compared with [(123)I]-2-iodo-L-tyrosine. The former tracer not only demonstrated faster blood clearance but also showed that the tracer uptake in the tumor reached its equilibrium with the blood pool activity faster, which led to faster and better tumor contrast. Moreover, both tracers could overcome an important limitation of (18)F-FDG-its high normal brain uptake.     

3-[123I]Iodo-L-alpha-methyl tyrosine transport into human fibroblasts and comparison with Ewing's sarcoma cells

The cellular transport systems and the transport kinetics of [123I]IMT uptake into non-malignant extracranial cells were characterized for the first time. Human fibroblasts were chosen as non-malignant extracranial cells as they are found ubiquitous in the body. [123I]IMT is exclusively transported into fibroblasts via the sodium independent system L. An apparent Michaelis constant K(m) = 116.2 +/- 18.9 microM and a maximum transport velocity V(max) = 191.6 +/- 13.9 pmol x (10(6) cells)(-1) x min(-1) were calculated for the sodium-independent transport. These results were compared with those determined in two malignantly transformed extracranial cell lines, the human Ewing's sarcoma cell lines VH-64 and CADO-ES-1.     

Practical benefit of [123I]FP-CIT SPET in the demonstration of the dopaminergic deficit in Parkinson's disease

Loss of striatal dopamine (DA) transporters in Parkinson's disease (PD) has been accurately assessed in vivo by single-photon emission tomography (SPET) studies using [¹²³I]-CIT. However, these studies have also shown that adequate imaging of the striatal DA transporter content can be performed only 20–30 h following the injection of [¹²³I]-CIT, which is not convenient for routine out-patient evaluations. Recently, a new ligand,N--fluoropropyl-2-carbomethoxy-3-(4-iodophenyl)tropane (FP-CIT), became available for in vivo imaging of the DA transporter. The faster kinetics of [¹²³I]FP-CIT have been shown to allow adequate acquisition as early as 3 h following injection. In the present study, loss of striatal DA transporters in five non-medicated PD patients was assessed on two consecutive SPET scans, one with [¹²³I]-CIT (24 h following injection) and one with [¹²³I]FP-CIT (3 h following injection). The ratios of specific to non-specific [¹²³I]FP-CIT uptake in the caudate nucleus and putamen were consistently 2.5-fold lower than those of [¹²³I]-CIT. However, when the uptake ratio of both ligands in these brain regions of patients was expressed as a percentage of the uptake ratio found in healthy controls, both the decrease and the variation of the data were similar. It is concluded on the basis of these findings that [¹²³I]FP-CIT seems as good as [¹²³I]-CIT for the assessment of the dopaminergic deficit in PD. The faster kinetics of [¹²³I]FP-CIT are a clear advantage.     

Kinetic modelling of [123I]CNS 1261--a potential SPET tracer for the NMDA receptor

N-(1-napthyl)-N'-(3-[(123)I]-iodophenyl)-N-methylguanidine ([(123)I]CNS 1261) is a novel SPET ligand developed for imaging the NMDA receptor intra-channel MK 801/PCP/ketamine site. Data was acquired in 7 healthy volunteers after bolus injection of [(123)I]CNS 1261. Kinetic modeling showed reversible tracer binding. Arterial and venous time-activity curves overlapped after 90 min. The rank order of binding was: Thalamus > striatum > cortical regions > white matter. This distribution concurs with [(11)C]-ketamine and [(18)F]-memantine PET studies. These data provide a methodological basis for further direct in vivo challenge studies.     

Quantification of nicotinic acetylcholine receptors in human brain using [123I]5-I-A-85380 SPET

The purpose of this study was to assess the utility of a new single-photon emission tomography ligand, [¹²³I]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine (5-I-A-85380), to measure regional nAChR binding in human brain. Six healthy nonsmoker subjects (two men and four women, age 33±15 years) participated in both a bolus (dose: 317±42 MBq) and a bolus plus constant infusion (dose of bolus: 98±32 MBq, B/I=6.7±2.6 h, total dose: 331±55 MBq) study. The study duration was 5–8 h and 14 h in the former and the latter, respectively. Nonlinear least-squares compartmental analysis was applied to bolus studies to calculate total (V_T) and specific (V_S) distribution volumes. A two-tissue compartment model was applied to identify V_S. V_T was also calculated in B/I studies. In bolus studies, V_T was well identified by both one- and two-tissue compartment models, with a coefficient of variation of less than 5% in most regions. The two-compartment model gave V_T values of 51, 22, 27, 32, 20, 19, 20, and 17 ml cm^–3 in thalamus, cerebellum, putamen, pons, and frontal, parietal, temporal, and occipital cortices, respectively. The two-compartment model did not identify V_S well. B/I studies provided poor accuracy of V_T measurement, possibly due to deviations from equilibrium conditions. These results demonstrate the feasibility of quantifying high-affinity type nAChRs using [¹²³I]5-I-A-85380 in humans and support the use of V_T measured by bolus studies.     

A comparison of99mTc-MIBI myocardial SPET with electron beam computed tomography in the assessment of coronary artery disease

We compared technetium-99m methoxyisobutylisonitrile (MIBI) myocardial perfusion single-photon emission tomography (SPET) (MPS) and electron beam computed tomography (EBCT) in order to assess their respective value in the detection of coronary artery disease (CAD).^99mTc-MIBI SPET (stress-resting) and EBCT studies were performed in 51 patients with suspected CAD who underwent coronary angiography (CAG). CAG showed that of the 51 patients, 36 had coronary stenosis 50% while 15 had normal results. A moderate positive rank correlation was found between coronary calcification detected by EBCT and MPS score (r _s=0.5283,P<0.01). The concordance between EBCT and MPS for the evaluation of CAD was 72.5% (37/51). The sensitivity of EBCT in detecting CAD in 51 patients was comparable to that of MPS (81% vs 94%, NS). However, the accuracy of EBCT was lower than that of MPS (78% vs 94%,P<0.025). As regards the detection of individual coronary artery disease, there was no significant difference in sensitivity between EBCT and MPS (65% vs 75%, NS); however, the specificity and accuracy of EBCT were lower than those of MPS (specificity: 77% vs 95%,P<0.005; accuracy 71% vs 85%,P<0.005). The sensitivity, specificity and accuracy of MPS in detecting single-vessel disease were higher than those of EBCT (sensitivity: 86% vs 42%,P<0.025; specificity: 96% vs 70%,P<0.025; accuracy: 93% vs 61%,P<0.005). However, no significant differences in the sensitivity, specificity and accuracy of MPS and EBCT were found in respect of multivessel disease. In conclusion:^99mTc-MIBI myocardial perfusion SPET and EBCT provide different information in the assessment of CAD. The sensitivity of EBCT for the detection of CAD is comparable with that of MPS; however, the specificity and accuracy of EBCT are lower than those of MPS. More reliable results will be obtained if both myocardial perfusion SPET and EBCT are performed.     

Validation of brain tumour imaging with p-[123I]iodo-l-phenylalanine and SPECT

Purpose The aims of this prospective study were to validate single-photon emission computed tomography (SPECT) with p-[¹²³I]iodo-l-phenylalanine (IPA) in brain tumours and to evaluate its potential for the characterisation of indeterminate brain lesions.Methods In 45 patients with indeterminate brain lesions or suspected progression of glioma, amino acid uptake was studied using IPA-SPECT and compared with the final diagnosis established by biopsy or serial imaging. After image fusion of IPA-SPECT and magnetic resonance imaging, the presence of tumour was visually determined by two independent observers. IPA uptake was quantified as the ratio between maximum uptake in the suspicious lesion and mean uptake in unaffected brain.Results Primary brain tumours were present in 35 cases (12 low-grade and 23 high-grade gliomas). Non-neoplastic brain lesions were confirmed in seven cases (three dysplasias, three inflammatory lesions, one lesion after effective therapy). Visual analysis showed a high concordance between the two observers (kappa=0.90, p<0.001), with sensitivity and specificity of 86% and 100% for the discrimination of primary brain tumours and non-neoplastic lesions. At 30 min p.i., IPA uptake in primary brain tumours was higher than that in non-neoplastic lesions (1.70±0.36 vs 1.14±0.18, p<0.05). Brain metastases showed no increased uptake (1.13±0.22, n=3). The persistent retention of IPA in low-grade gliomas without disruption of the blood–brain barrier was visualised up to 24 h p.i. Low-grade and high-grade gliomas showed equivalent IPA uptake (1.72±0.37 vs 1.67±0.36 at 30 min, p=0.745).Conclusion IPA shows long and specific retention in gliomas. IPA is a promising and safe radiopharmaceutical for the visualisation of gliomas and the characterisation of indeterminate brain lesions.     

L-3-[123I]Iodo-alpha-methyltyrosine scintigraphy in carcinoid tumors: correlation with biochemical activity and comparison with [111In-DTPA-D-Phe1]-octreotide imaging.

Carcinoid tumors can produce serotonin (5-hydroxytryptamine) and catecholamines from the precursors tryptophan and tyrosine. Our aim was to evaluate the tyrosine analog L-3-[123I]iodo-alpha-methyltyrosine (IMT) in the detection and the determination of biochemical activity of these tumors in comparison with 111In-labeled [diethylenetriaminepentaacetic acid (DTPA)-D-Phe1]-octreotide (111In-octreotide) scintigraphy. METHODS: SPECT and planar whole-body imaging were performed 15 min after administration of 300 MBq IMT in 22 patients with metastatic carcinoid tumors. The number of lesions detected was compared with the number detected by 111In-octreotide scintigraphy. The size and intensity of uptake of all lesions were graded using a simple scoring system, yielding a total body uptake score for both tracers. These scores were compared (nonparametric correlation) with biochemical markers of serotonin and catecholamine metabolism. RESULTS: IMT SPECT detected only 63 of 145 lesions detected by 111In-octreotide imaging (43%). IMT SPECT performance was best in the liver (60% detection rate). Both IMT uptake and 111In-octreotide uptake scores correlated with markers of serotonin metabolism (respective values for urinary 5-hydroxyindoleacetic acid: r = 0.67 and 0.48, P < 0.001 and 0.05; for urinary serotonin: r = 0.56 and 0.40, P = 0.002 and 0.05; and for platelet serotonin: r = 0.57 and 0.45, P < 0.01 and 0.05). No correlation with adrenaline or noradrenaline metabolites was found. However, IMT uptake, but not 111In-octreotide uptake, correlated with dopamine metabolite excretion (homovanillic acid: r = 0.60, P < 0.05; and dopamine relative sum: r = 0.61, P < 0.05). IMT uptake was higher in patients with increased dopamine metabolite excretion (P = 0.05). CONCLUSION: IMT uptake can be demonstrated in carcinoid lesions, but the method detected only 43% of carcinoid lesions that were positive on 111In-octreotide scintigraphy. Uptake of both tracers is related to the serotonin secretory activity. However, IMT uptake, but not 111In-octreotide uptake, was related to tumor dopamine metabolism. These findings may be of interest in the metabolic targeting of carcinoids.     

123I] beta-CIT binding and SPET compared with clinical diagnosis in parkinsonism

The largest group of neurodegenerative disorders are extrapyramidal diseases, especially parkinsonism. The development of the cocaine derivative [123I] beta-CIT and single photon emission tomography (SPET) may help in the diagnosis of these patients. The aim of this study was to demonstrate the diagnostic value of this method and its relationship with clinical data. Ninety-eight individuals were investigated: 11 healthy volunteers, 58 patients with idiopathic Parkinson's disease (IPD) and 29 patients with symptomatic parkinsonism (SPD). All patients with parkinsonism were staged according to the clinical classification of Hoehn and Yahr. [123I] beta-CIT was injected intravenously and a triple-headed camera was used to obtain images 20 h later. The images were evaluated visually and semi-quantitatively to obtain comparable values (ratio: specific to non-displaceable binding). The ratios differed significantly between controls and IPD patients. A significant correlation also existed between the ratios and clinical stages. In 11 hemiparkinsonian patients, a significantly diminished ratio was demonstrated not only contralateral to the affected side, but also in the clinically silent striatum. A clinical threshold at a reduction of 34% [123I] beta-CIT binding was calculated in this group. The ratios of all SPD patients in our study did not differ significantly from those of the healthy volunteers. According to the clinical degree of symptoms, the more severe subgroup showed a diminished mean ratio of 22% and therefore could not be clearly differentiated from mild IPD. In contrast, ratios were significantly different when comparing groups of the same clinical severity. We conclude that this method is not only a powerful diagnostic tool in IPD patients, but it is also possible to differentiate between IPD and SPD patients, if clinical aspects are also included.     

FLAIR MR sequence in the diagnosis and follow-up of low-grade astrocytomas

AIM: To evaluate the sensitivity of fluid-attenuated inversion recovery (FLAIR) sequence in the diagnosis and follow-up of the patients with low-grade astrocytomas compared with T2-weighted (T2W) sequence. METHODS: Twenty-four patients with biopsy-confirmed low-grade astrocytoma (age range, 15-66 years) underwent T1-weighted (T1W), T2W and FLAIR imaging with a superconducting unit 1.0 T. FLAIR images were qualitatively evaluated by comparison with T2W images by the three experienced neuroradiologists. To evaluate the diagnostic value of FLAIR, the neuroradiologists individually assessed the possibilities of the detection of lesions, as well as the possibilities of the differentiation of tumor from the surrounding edema on FLAIR vs. T2W images. Every examiner ranked FLAIR sequence vs. T2W in three degrees: worse, equal and better. RESULTS: The comparison of FLAIR with T2W spin-echo (SE) images with regard to the detection of the lesions showed that 82.8% of FLAIR studies were superior, 17.2% were of similar diagnostic value, and none was inferior to the T2W images. The comparison of images with regard to the differentiation of tumor boundaries vs. surrounding edema showed that 92.5% of FLAIR studies were superior, 7.5% were of similar diagnostic value, and none was inferior to the T2W images. CONCLUSION: Our results were similar to the previous studies' results concerning the advantages of FLAIR sequence in the diagnosis of low grade astrocytomas over T2W sequence. FLAIR was better at showing different tumor components, and at distinguishing CSF from the cystic component, and the postoperative cavity, compared with T2W images. Our conclusion was that FLAIR could be routinely used in the evaluation and follow-up of low-grade astrocytomas.     

Characterization of 3-[123I]iodo-L-alpha-methyl tyrosine ([123I]IMT) transport into human Ewing's sarcoma cells in vitro

3-[(123)I]Iodo-L-alpha-methyl tyrosine ([(123)I]IMT) scintigraphy of extracranial malignant tumors has been described, but little is known about the transport systems involved in [(123)I]IMT uptake into extracranial tumor cells. Here, the precise kinetics of [(123)I]IMT transport into human Ewing's sarcoma cells (VH-64) was determined. The apparent Michaelis constant was of high affinity value (K(m)=41.7+/-3.9 microM) and maximum transport velocitiy amounted to V(max)=20.7+/-0.6 nmol x mg protein(-1) x 10 min(-1). Inhibition experiments revealed the predominance of [(123)I]IMT uptake via sodium-independent system L.     

Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers

Dopamine transporter imaging is a valuable tool to investigate the integrity of the dopaminergic neurons. To date, several reports have shown an age-associated decline in dopamine transporters in healthy volunteers. Although animal studies suggest an effect of gender on dopamine transporter density, this gender effect has not yet been confirmed in human studies. To study the influence of age and gender on dopamine transporter imaging in healthy volunteers, we performed single-photon emission tomography imaging with [¹²³I]FP-CIT to quantify dopamine transporters. Forty-five healthy volunteers (23 males and 22 females) were included, ranging in age from 18 to 83 years. SPET imaging was performed 3 h after injection of ±110 MBq [¹²³I]FP-CIT. An operator-independent volume of interest analysis was used for quantification of [¹²³I]FP-CIT binding in the striatum. The ratio of specific striatal to non-specific [¹²³I]FP-CIT binding was found to decrease significantly with age. Moreover, we found a high variance in [¹²³I]FP-CIT binding in young adults. Finally, females were found to have significantly higher [¹²³I]FP-CIT binding ratios than males. This effect of gender on [¹²³I]FP-CIT binding ratios was not related to age. The results of this study are consistent with findings from previous studies, which showed that dopamine transporter density declines with age. The intriguing finding of a higher dopamine transporter density in females than in males is in line with findings from animal studies. Received 29 January 2000 and in revised form 27 March 2000     

Effect of age and gender on dopamine transporter imaging with [123I]FP-CIT SPET in healthy volunteers

Dopamine transporter imaging is a valuable tool to investigate the integrity of the dopaminergic neurons. To date, several reports have shown an age-associated decline in dopamine transporters in healthy volunteers. Although animal studies suggest an effect of gender on dopamine transporter density, this gender effect has not yet been confirmed in human studies. To study the influence of age and gender on dopamine transporter imaging in healthy volunteers, we performed single-photon emission tomography imaging with [123I]FP-CIT to quantify dopamine transporters. Forty-five healthy volunteers (23 males and 22 females) were included, ranging in age from 18 to 83 years. SPET imaging was performed 3 h after injection of +/-110 MBq [123I]FP-CIT. An operator-independent volume of interest analysis was used for quantification of [123I]FP-CIT binding in the striatum. The ratio of specific striatal to non-specific [123I]FP-CIT binding was found to decrease significantly with age. Moreover, we found a high variance in [123I]FP-CIT binding in young adults. Finally, females were found to have significantly higher [123I]FP-CIT binding ratios than males. This effect of gender on [123I]FP-CIT binding ratios was not related to age. The results of this study are consistent with findings from previous studies, which showed that dopamine transporter density declines with age. The intriguing finding of a higher dopamine transporter density in females than in males is in line with findings from animal studies.