Biomedical subjects

E A van Royen

Publications and source records attributed to E A van Royen.

At least 19 recordsLinked to original sources

PubMed1999

Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism.

Parkinsonism is a feature of a number of neurodegenerative diseases, including Parkinson's disease, multiple system atrophy and progressive supranuclear palsy. The results of post-mortem studies point to dysfunction of the dopaminergic neurotransmitter system in patients with parkinsonism. Nowadays, by using single-photon emission tomography (SPET) and positron emission tomography (PET) it is possible to visualise both the nigrostriatal dopaminergic neurons and the striatal dopamine D2 receptors in vivo. Consequently, SPET and PET imaging of elements of the dopaminergic system can play an important role in the diagnosis of several parkinsonian syndromes. This review concentrates on findings of SPET and PET studies of the dopaminergic neurotransmitter system in various parkinsonian syndromes.

Carrier Proteins↗

PubMed1998

Biodistribution and dosimetry of iodine-123-labelled Z-MIVE: an oestrogen receptor radioligand for breast cancer imaging.

This study reports on the distribution and radiation dosimetry of iodine-123-labelled cis-11beta-methoxy-17alpha-iodovinyloestradiol (Z-[123I]MIVE), a promising radioligand for imaging of oestrogen receptors (ERs) in human breast cancer. Whole-body scans were performed up to 24 h after intravenous injection of 138-193 MBq Z-[123I]MIVE in five healthy female volunteers, four with and one without thyroid blockade. Blood samples were taken at various times up to 24 h after injection. Urine was collected up to 24 h after injection in order to calculate renal clearance and to aid in the interpretation of whole-body clearance, including faecal excretion. Time-activity curves were generated for the thyroid, heart, brain, breasts and liver, by fitting the organ-specific geometric mean counts, obtained from regions of interest, to a multicompartmental model. The MIRD formulation, using 11 source organs, was applied to calculate the absorbed radiation doses for various organs upon administration of Z-[123I]MIVE. The images showed rapid hepatobiliary excretion which resulted in good imaging conditions for the thoracic region. Imaging of the abdominal region was impeded due to extensive bowel activity. Diffuse uptake and retention of activity was seen in breast tissue, the breast-to-non-specific uptake ratio increasing over time. Z-[123I]MIVE was cleared by both the kidneys and the gastrointestinal tract. At 50 h p.i. the mean excretion in urine was predicted to be 58%+/-14% (SD) and that in faeces 31%+/-19%. If the thyroid was not blocked, it was the most critical organ (0.33 mGy/MBq). In general, the excretory organs received the highest absorbed doses, i.e. the lower and upper large intestinal walls (0.11 and 0.098 mGy/MBq, respectively), the urinary bladder wall (0.090 mGy/MBq), the gallbladder wall (0.087 mGy/MBq) and the small intestine (0.043 mGy/MBq). The average effective dose equivalent of Z-[123I]MIVE was estimated to be 0.033 mSv/MBq. The amount of Z-[123I]MIVE required for adequate breast cancer ER imaging results in an acceptable effective dose equivalent to the patient.

Adult↗

PubMed1998

Iodine-123 labelled nor-beta-CIT binds to the serotonin transporter in vivo as assessed by biodistribution studies in rats.

Iodine-123 labelled 2beta-carbomethoxy-3beta-4-iodophenylnortropane (nor-beta-CIT), a radioiodinated cocaine analogue, was evaluated as an agent for the in vivo labelling of serotonin transporters by biodistribution studies in rats. Intravenous injection of [123I]nor-beta-CIT resulted in high accumulation of radioactivity in brain areas with high densities of serotonin (hypothalamus) and dopamine transporters (striatum), although the binding was less pronounced in the hypothalamus. While binding of [123I]nor-beta-CIT in the hypothalamus was blocked significantly by fluvoxamine (a selective serotonin transporter blocker) but not by GBR12,909 (a selective dopamine transporter blocker), the opposite was observed in the striatum. The results of this study indicate that [123I]nor-beta-CIT, although not being a selective radioligand, binds specifically to serotonin transporters in the hypothalamus in vivo and thus suggest that [123I]nor-beta-CIT promises to be a suitable radioligand for single-photon emission tomography imaging of serotonin transporters in humans.

Animals↗

PubMed1998

Drug-naive patients with Parkinson's disease in Hoehn and Yahr stages I and II show a bilateral decrease in striatal dopamine transporters as revealed by [123I]beta-CIT SPECT.

Ten healthy subjects and 16 patients with early Parkinson's disease (PD) were examined with single photon emission computed tomography (SPECT) and [123I]beta-CIT, a ligand for the dopamine (DA) transporter. Only drug-naive patients were examined since the expression of and binding to DA transporters may be influenced by dopaminergic medication. The main finding was a significant reduction in [123I]beta-CIT binding in the ipsi- and contralateral striatal regions, especially in the putamen, which showed a mean reduction of 65% of the control mean. Discriminant function analysis of the putaminal [123I]beta-CIT binding measures classified 100% of the cases in the correct group. Disease severity correlated negatively and highly significantly with the binding measures. Tremor ratings did not correlate with the SPECT measures, whereas rigidity, and to a lesser extent bradykinesia, did. Patients with unilateral PD showed a bilateral loss of striatal DA transporters. Our findings indicate that with [123I]beta-CIT SPECT it is possible to diagnose PD in subjects with very mild symptoms and signs. Moreover, finding a bilateral loss of striatal DA transporters in patients with unilateral PD also suggests that it may be possible to identify subjects in the preclinical phase of the disease.

Adult↗

PubMed1998

Lack of perfusion enhancement after administration of nicotinamide and carbogen in patients with glioblastoma: a 99mTc-HMPAO SPECT study.

BACKGROUND: Nicotinamide (NAM) and carbogen both have been shown to enhance the radiation effect in rodent tumour models and are currently being tested in clinical trials. These agents have demonstrated to act against hypoxia and one of their underlying mechanisms could be an increase of tumour blood perfusion. PURPOSE: To analyse the effect of both agents on normal brain perfusion and tumour perfusion in patients with glioblastoma. MATERIALS AND METHODS: Nineteen patients with glioblastoma were studied with 99mtechnetium-hexamethylpropyleneamine oxime single photon emission computed tomography (99mTc-HMPAO SPECT) before and after administration of carbogen and/or NAM. Another six patients were studied with the same procedure but without any flow modulator and were used as controls. RESULTS: Although the variations between patients were large, no significant enhancement in mean tumour and normal brain perfusion could be demonstrated with NAM or carbogen compared to the control patients. Also no consistent changes in the mean perfusion ratio between tumour and surrounding normal brain were found, suggesting an absence of a selective perfusion effect. CONCLUSIONS: No significant influence of carbogen and/or NAM on tumour perfusion and normal brain perfusion could be detected with SPECT in patients with glioblastoma.

Analysis of Variance↗

PubMed1998

Synthesis, estrogen receptor binding, and tissue distribution of a new iodovinylestradiol derivative (17alpha,20E)-21-[123I]Iodo-11beta-nitrato-19-norp regna-1,3,5 (10),20-tetraene-3,17-diol (E-[123I]NIVE).

We have synthesized and evaluated E-11beta-nitrato-17alpha-iodovinylestradiol (E-NIVE; E-3c) and its 123I-labelled form, as a new potential radioligand for imaging of estrogen receptor (ER)-positive human breast tumors. E-[123I]NIVE was prepared by stereospecific iododestannylation of the E-tri-n-butylstannylvinyl precursor (E-2c), obtained from reaction of 11beta-nitrato-estrone (8) with E-tributylstannylvinyllithium. In competitive binding studies, E-NIVE proved to have high binding affinity for both the rat and the human ER (Ki 280-730 pM), without significant binding to human sex hormone binding globulin. Distribution studies in normal and mammary tumor-bearing rats showed specific ER-mediated uptake of E-[123I]NIVE in the estrogen target tissues, i.e., uterus, ovaries, pituitary, and hypothalamus, but not in the mammary tumors. Selective retention in these target tissues, including tumor tissue, resulted in significant increases over time for the target tissue-to-muscle uptake ratios, but not for the target tissue-to-fat uptake ratios. The tumor-to-fat uptake ratio even appeared constantly below 1. In the primary estrogen target tissues, E-[123I]NIVE displayed high specific ER-mediated uptake and retention, which resulted in moderate target-to-nontarget tissue uptake ratios. In contrast, in tumor tissue, E-[123I]NIVE uptake appeared to be rather low and not ER-specific. As a consequence, E-[123I]NIVE appears to be a less favorable radioligand for ER imaging in breast cancer than the previously studied stereoisomers of 11beta-methoxy-17alpha-[123I]iodovinylestradiol (E- and Z-[123I]MIVE; [123I]E- and [123I]Z-3b).

Animals↗

PubMed1998

New iodinated progestins as potential ligands for progesterone receptor imaging in breast cancer. Part 1: Synthesis and in vitro pharmacological characterization.

Five putative iodinated progesterone receptor (PR) binding ligands were synthesized and evaluated as potential imaging agents for PR-positive human breast tumours. Two compounds (E- and Z-17-hydroxy-21-iodo-19-nor-17alpha-pregna-4,20-dien-3-one; E- and Z-IPG1) were previously described, but are re-evaluated. The other three were novel compounds: two nortestosterone analogues derived from ORG 3236 (E- and Z-13-ethyl-17-hydroxy-21-iodo-11-methylene-18,19-dinor-17alpha-pre gna-4,20-diene-3-one; E- and Z-IPG2) and one norprogesterone analogue derived from ORG 2058 (21-[4-iodophenoxy]-16alpha-ethyl-19-norpregn-4-ene-3, 20-dione; IPG3). The E-iodovinyl nortestosterone compounds were obtained by a new route of synthesis. Competitive binding studies were performed to determine their binding affinities for the PR in three types of tissue (human MCF-7 breast tumour cells and rat uterine and mammary tumour tissue) and for the androgen receptor (AR) in human MCF-7 breast tumour cells, as well as for the sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) in human plasma. All four 17alpha-iodovinyl nortestosterone derivatives displayed high binding affinity for the human PR, that of Z-IPG1 and E- and Z-IPG2 being even higher than that of ORG2058. Their affinities for the rat PR were somewhat lower, especially those of both E-isomers. The affinity of IPG3 was lower for both the human and rat PR. The nortestosterone derivatives also showed AR binding, the relative binding affinities ranging from 4.3 to 17.0% as compared with 5alphaDHT. Additionally, neither of these steroids displayed any significant binding to either SHBG or CBG in human plasma. We conclude that the in vitro binding properties of all four 17alpha-iodovinyl nortestosterone derivatives warrant evaluation of the distribution characteristics of their 123I-labelled analogues to determine their usefulness as PR imaging agents.

Animals↗

PubMed1998

New iodinated progestins as potential ligands for progesterone receptor imaging in breast cancer. Part 2: In vivo pharmacological characterization.

On the basis of the observed high selective binding to both the human and rat progesterone receptor (PR) in vitro, three 17alpha-iodovinyl-substituted nortestosterone derivatives, i.e., the Z-isomer of 17alpha-iodovinyl-19-nortestosterone (Z-IVNT; Z-IPG1) and both the stereoisomers of 17alpha-iodovinyl-18-methyl-11-methylene-19-nortestosterone (E- and Z-IPG2), were selected for radio-iodination and subsequently evaluated as potential radioligands for PR imaging in human breast cancer. Their target tissue uptake, retention, and uptake selectivity were studied in female rats. The distribution studies revealed that PR-mediated uptake in the uterus and ovaries could only be demonstrated for Z-[123I]IPG2. The target tissue uptake selectivity was, however, low, with the highest uterus-to-nontarget tissue uptake ratios observed at 2-4 h postinjection (p.i.), being 4.4, 1.8, and 7.4 for the uterus-to-blood, -fat, and -muscle ratio, respectively. For Z-[123I]IPG2, distribution was also studied in dimethylbenzanthracene (DMBA)-induced mammary tumour-bearing rats and in normal rabbits. Mammary tumour uptake of Z-[123I]IPG2 in the mammary tumour-bearing rat was also found to be PR-specific. In rabbits, higher selective target tissue uptake of Z-[123I]IPG2 was observed than in rats, resulting in uterus-to-blood, -fat, and -muscle ratios of 6.6, 2.2, and 21.3 at 2-4 h p.i., respectively. In conclusion, Z-[123I]IPG2, which displayed high binding affinity for both the human and rat PR in vitro, showed specific PR-mediated target tissue uptake in rats and rabbits in vivo, the uptake selectivity being highest in the latter. Because the binding characteristics appeared to vary between species, a pilot study in breast cancer patients may be needed to decide whether Z-[123I]IPG2 can be of potential use as PR imaging agent in breast cancer.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1998

Gastric transit and pharmacodynamics of a two-millimeter enteric-coated pancreatin microsphere preparation in patients with chronic pancreatitis.

It has been suggested that enteric-coated pancreatin microsphere (ECPM) preparations with sphere sizes larger than 1.7 mm pass through the stomach at a slower rate than a meal and therefore may be less efficacious in restoring pancreatic enzyme activity than preparations with smaller sphere sizes. The aim of this study was to investigate the gastric transit profile of a 2-mm ECPM preparation in relation to that of a solid meal and to simultaneously measure enzyme activities in eight patients with pancreatic exocrine insufficiency due to chronic pancreatitis. Gastric transit was assessed by double-isotope scintigraphy. A pancake was labeled with 99mTc. A 2-mm ECPM preparation was labeled with 171Er. Intraluminal pancreatic enzyme activities were assessed during a 6-hr period with the cholesteryl-[14C]octanoate breath test (for carboxyl ester lipase activity) and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid/p-aminosalicylic acid (NBT-PABA/PAS) test (for chymotrypsin activity). The ECPM preparation passed through the stomach more rapidly (median 24 min) than the pancake (median 52 min, P < 0.05). During ECPM therapy, mean cumulative 14CO2 outputs rose significantly from 30% to 70% (P < 0.05), but remained below outcomes in healthy volunteers. Mean cumulative plasma PABA concentrations rose significantly from 46% to 87% (P < 0.05) and were not significantly different from outcomes in healthy volunteers. In chronic pancreatitis, a 2-mm ECPM preparation does not pass through the stomach more slowly than a solid meal, but in fact faster. Digestion of ester lipids and proteins showed an improvement to subnormal and normal levels, respectively.

4-Aminobenzoic Acid↗

PubMed1998

Human biodistribution and dosimetry of [123I]FP-CIT: a potent radioligand for imaging of dopamine transporters.

This study reports on the biodistribution and radiation dosimetry of iodine-123-labelled N-omega-(flu- oropropyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I]FP-CIT), a promising radioligand for the imaging of dopamine transporters. In 12 healthy volunteers, conjugate whole-body scans were performed up to 48 h following intravenous injection of approximately 100 MBq [123I]FP-CIT. Attenuation correction was performed using a transmission whole-body scan obtained prior to injection of the radioligand, employing a 123I flood source. Blood samples were taken and urine was freely collected up to 48 h after injection of the radiotracer. For each subject, the percentage of injected activity measured in regions of interest over brain, striatum, lungs and liver were fitted to a multicompartmental model to give time-activity curves. The cumulative urine activity curve was used to model the urinary excretion rate and, indirectly, to predict faecal excretion. Using the MIRD method, nine source organs were considered in estimating absorbed radiation doses for organs of the body. The images showed rapid lung uptake and hepatobiliary excretion. Diffuse uptake and retention of activity was seen in the brain, especially in the striatum. At 48 h following the injection of [123I]FP-CIT, mean measured urine excretion was 60%+/-9% (SD), and mean predicted excretion in faeces was 14%+/-1%. In general, the striatum received the highest absorbed dose (average 0.23 mGy/MBq), followed by the urinary bladder wall (average 0.054 mGy/MBq) and lungs (average 0.043 mGy/MBq). The average effective dose equivalent of [123I]FP-CIT was estimated to be 0.024 mSv/MBq. The amount of [123I]FP-CIT required for adequate dopamine transporter imaging results in an acceptable effective dose equivalent to the patient.

Adult↗

PubMed1998

Iodine-123-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iod ophenyl)tropane SPECT in healthy controls and early-stage, drug-naive Parkinson's disease.

UNLABELLED: The aims of this study were to investigate whether the loss of striatal dopamine transporters in early and drug-naive patients with Parkinson's disease could be demonstrated by means of 123I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodoph enyl)tropane (123I-FP-CIT) SPECT in a 1-day protocol and whether the SPECT measures were correlated with disease severity. METHODS: Twenty-one early-stage and drug-naive Parkinson's disease patients (age range 42-73 yr; mean age 55.5 yr) and 14 healthy controls (age range 28-83 yr; mean age 53.6 yr) were examined. SPECT image acquisition was always performed at 3 hr postinjection. The ratio of specific to nonspecific striatal 123I-FP-CIT binding was used as the outcome measure. RESULTS: All striatal 123I-FP-CIT ratios were significantly lower in the Parkinson's disease group compared to those in the control group. The mean reduction in the putamen was 57% of the control mean, and that in the caudate nucleus was 29% of the control mean. Patients with unilateral Parkinson's disease showed a bilateral loss of striatal 123I-FP-CIT binding. Discriminant function analysis, using the 123I-FP-CIT SPECT data of the ipsilateral and contralateral putamen, predicted group membership in all cases; the contralateral putamen accounted for the greatest difference between the Parkinson's disease patients and the controls. In the control group, a clear decline in 123I-FP-CIT binding was found with aging, amounting to 9.6%/decade. Unexpectedly, in the Parkinson's disease group, regression analysis revealed that neither severity of disease nor age accounted for a significant part of the variance in striatal SPECT measures. CONCLUSION: Our findings indicate that 123I-FP-CIT SPECT is a reliable method to discriminate between early, drug-naive Parkinson's disease patients and healthy controls and to identify patients in the preclinical phase of Parkinson's disease. Possibly due to the relatively homogeneous group of Parkinson's disease patients and the use of a suboptimal outcome measure, no significant correlations were found between striatal 123I-FP-CIT binding ratios and disease severity, such as were established earlier with 123I-beta-CIT. Further research is necessary to interpret these findings.

Adult↗

PubMed1998

Imaging of dopamine transporters with iodine-123-FP-CIT SPECT in healthy controls and patients with Parkinson's disease.

UNLABELLED: Several SPECT studies reported decreased striatal 123I-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodoph enyl)nortropane ([123I]FP-CIT) binding in patients with Parkinson's disease. For application in routine clinical studies, information on the reliability and reproducibility of the [123I]FP-CIT SPECT technique is critical. This study reports on the reliability and reproducibility of [I23I]FP-CIT SPECT in healthy control subjects and patients with Parkinson's disease using two different analysis protocols: the conventional region of interest (ROI) protocol and a newly developed, fully automatic, operator-independent volume of interest (VOI) protocol. METHODS: We performed repeated [123I]FP-CIT SPECT scans in 6 healthy control subjects and 10 patients with Parkinson's disease to measure scan-to-scan variations. Scintigraphic data were analyzed 3 hr after injection of the radiotracer. RESULTS: In controls, the mean test/retest for the ratio of the striatal-to-nonspecific [123I]FP-CIT uptake were (3.79 +/- 0.67/3.82 +/- 0.74) and (4.16 +/- 0.70/4.08 +/- 0.97) for the ROI and VOI technique, respectively. No significant differences were measured between test/retest studies. The mean test/retest variability for the ROI technique was low (7.25%) with excellent reliability (rho = 0.99). In addition, the mean test/retest variability for the VOI technique was also low (7.47%) with very high reliability (rho = 0.95). In Parkinson's disease patients, we found mean test/retest for the striatal-to-nonspecific [123I]FP-CIT ratio of (1.78 +/- 0.23/1.79 +/- 0.25) and (1.83 +/- 0.31/1.85 +/- 0.35) using the ROI and VOI technique, respectively. Also in patients, these results did not differ significantly between test/retest studies. The mean test/retest variability for the ROI technique was low (7.90%) with excellent reliability (rho = 1.00). In addition, the mean test/retest variability for the VOI technique was also low (7.36%) with high reliability (rho = 0.96). CONCLUSION: Reliable and reproducible results were obtained with the ROI, as well as the VOI technique, for the analysis of striatal dopamine transporters with [123I]FP-CIT SPECT in healthy controls and Parkinson's disease patients. The use of an operator-independent method will be a great advantage in routine clinical studies.

Aged↗

PubMed1997

Generation of HER-2/neu-specific cytotoxic neutrophils in vivo: efficient arming of neutrophils by combined administration of granulocyte colony-stimulating factor and Fcgamma receptor I bispecific antibodies.

Abs are able to induce inflammatory antitumor responses by recruiting IgG Fc receptor (FcgammaR)-bearing cytotoxic effector cells. We recently described the capacity of the high affinity FcgammaRI (CD64) to trigger cytotoxic activity of neutrophils (PMN) during granulocyte CSF (G-CSF) treatment. To take advantage of FcgammaRI as a cytotoxic trigger molecule on PMN, two Ab constructs were prepared. We show that a chimeric human IgG1 Ab (Ch520C9) and an anti-FcgammaRI bispecific Ab (BsAb; 22x520C9), both directed to the proto-oncogene product HER-2/neu, interact with FcgammaRI. In addition, both Ab constructs mediate enhanced lysis of HER-2/neu-expressing tumor cells by G-CSF-primed PMN. However, engagement of FcgammaRI by Ch520C9 was inhibited by human serum IgG, thereby abrogating the enhanced Ch520C9-mediated cytotoxicity. BsAb 22x520C9, which binds FcgammaRI outside the ligand binding domain, effectively recruits the cytotoxic potential of FcgammaRI on G-CSF-primed PMN regardless of the presence of human serum. These results indicate that under physiologic conditions, serum IgG impairs activation of FcgammaRI-mediated cytotoxicity by conventional antitumor Abs. The IgG blockade can be circumvented with anti-FcgammaRI BsAbs. Using human FcgammaRI transgenic mice we demonstrate that BsAb 22x520C9 is able to engage FcgammaRI in vivo. BsAb 22x520C9 injected i.v. was readily detected on circulating PMN of G-CSF-treated transgenic animals. In addition, we showed that PMN remain "armed" with BsAb 22x520C9 during migration to inflammatory sites, and that after isolation such PMN specifically lyse HER-2/neu-expressing tumor cells. These results point to the possibility of targeting anti-FcgammaRI BsAbs to G-CSF-primed PMN in vivo, endowing them with specific anti-tumor activity.

Animals↗

PubMed1997

Comparative effects of enteric-coated pancreatin microsphere therapy after conventional and pylorus-preserving pancreatoduodenectomy.

BACKGROUND: A comparative study was performed between patients with exocrine pancreatic insufficiency after conventional pancreatoduodenectomy (Whipple's procedure) and pylorus-preserving pancreatoduodenectomy (PPPD). In these patients the pharmacodynamics of 2-mm enteric-coated pancreatin microspheres (ECPMs) and their gastric transit time in relation to that of a solid meal were investigated. The efficacy of ECPM preparations may differ after Whipple's procedure compared with PPPD, because the latter procedure does not include gastrectomy. METHODS: Gastric transit was assessed by double-isotope scintigraphy. A pancake meal was labelled with 99mTc. ECPMs were cold-labelled with 170Er and neutron activated shortly before ingestion to enable imaging with a gamma camera. Intraluminal pancreatic enzyme activity was assessed during a 6-h period with two indirect tests: the cholesteryl [14C]octanoate breath test and the N-benzoyl-L-tyrosyl-p-aminobenzoic acid-p-aminosalicylic acid (NBT-PABA-PAS) test. RESULTS: In patients who had Whipple's procedure, the gastric transit time of ECPMs and of the pancake meal was not significantly different. The outcome of the indirect pancreatic function tests during enzyme supplementation was comparable, and not significantly different, from that in healthy volunteers. In patients who had PPPD, however, the gastric transit time of microspheres was greatly delayed compared with that of the pancake meal (P < 0.05). Improvement in the outcome of the indirect pancreatic function tests during enzyme supplementation was much less and remained well below that of healthy volunteers (P < 0.05). CONCLUSION: In cases of exocrine pancreatic insufficiency after Whipple's procedure, 2-mm ECPM treatment adequately restores pancreatic enzyme activity. Following PPPD, however, ECPM treatment is often ineffective because the microspheres are retained in the stomach. In these patients, use of conventional powdered pancreatin enzyme preparations may improve the efficacy of treatment.

4-Aminobenzoic Acid↗

PubMed1997

IBZM- and CIT-SPECT of the dopaminergic system in parkinsonism.

Parkinsonism is most of the time caused by idiopathic Parkinson's disease (IPD). Considering the differences in therapeutic response and prognosis, in vivo discrimination between IPD and "parkinsonism-plus" syndromes is important. Recently, ligands have become available for imaging the pre- and postsynaptic dopaminergic system by Single Photon Emission Computed Tomography (SPECT). Visualization of postsynaptic D2 dopamine receptors using 123I-iodobenzamide (123I-IBZM) may contribute to the differential diagnosis between IPD and "parkinsonism-plus" syndromes as IPD is a pure presynaptic disease. Imaging of the presynaptic dopamine transporters using [123I] beta-CIT (2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane) may be used as a diagnostic technique. Early disease detection in subjects suspected to be at risk for developing IPD has become possible using [123I] beta-CIT or other ligands for the dopamine transporter. Furthermore, with SPECT one is probably able to monitor in an objective way the efficacy of new pharmacological therapies.

Benzamides↗

PubMed1997

Demonstration of a reduction in muscarinic receptor binding in early Alzheimer's disease using iodine-123 dexetimide single-photon emission tomography.

Decreased muscarinic receptor binding has been suggested in single-photon emission tomography (SPET) studies of Alzheimer's disease. However, it remains unclear whether these changes are present in mildly demented patients, and the role of cortical atrophy in receptor binding assessment has not been investigated. We studied muscarinic receptor binding normalized to neostriatum with SPET using [123I]4-iododexetimide in five mildly affected patients with probable Alzheimer's disease and in five age-matched control subjects. Region of interest (ROI) analysis was performed in a consensus procedure blind to clinical diagnosis using matched magnetic resonance (MRI) images. Cortical atrophy was assessed by calculating percentages of cerebrospinal fluid in each ROI. An observer study with three observers was conducted to validate this method. Alzheimer patients showed statistically significantly less [123I]4-iododexetimide binding in left temporal and right temporo-parietal cortex compared with controls, independent of age, sex and cortical atrophy. Mean intra-observer variability was 3.6% and inter-observer results showed consistent differences in [123I]4-iododexetimide binding between observers. However, differences between patients and controls were comparable among observers and statistically significant in the same regions as in the consensus procedure. Using an MRI-SPET matching technique, we conclude that [123I]4-iododexetimide binding is reduced in patients with mild probable Alzheimer's disease in areas of temporal and temporo-parietal cortex.

Aged↗

PubMed1997

Assessment of endogenous dopamine release by methylphenidate challenge using iodine-123 iodobenzamide single-photon emission tomography.

This double-blind, placebo-controlled study assessed pharmacologically induced endogenous dopamine (DA) release in healthy male volunteers (n=12). Changes in endogenous DA release after injection of the psychostimulant drug methylphenidate were evaluated by single-photon emission tomography (SPET) and constant infusion of iodine-123 iodobenzamide ([123I]IBZM), a D2 receptor radioligand that is sensitive to endogenous DA release. Methylphenidate induced displacement of striatal [123I]IBZM binding, resulting in a significantly decrease in the specific to non-specific [123I]IBZM uptake ratio (average: 8.6%) in comparison with placebo (average: -1.9%). Moreover, injection of methylphenidate induced significant behavioural responses on the following items: excitement, anxiety, tension, and mannerisms and posturing. The results of this study demonstrate the feasibility of using constant infusion of [123I]IBZM and SPET imaging to measure endogenous DA release after methylphenidate challenge and to investigate neurochemical aspects of behaviour.

Adult↗

PubMed1997

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]beta-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]beta-CIT, which is not convenient for routine out-patient evaluations. Recently, a new ligand, N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(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]beta-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]beta-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]beta-CIT for the assessment of the dopaminergic deficit in PD. The faster kinetics of [123I]FP-CIT are a clear advantage.

Brain↗