Diagnosis of medullary carcinoma of the thyroid (MCT) by calcitonin assay using monoclonal antibodies: criteria for the pentagastrin stimulation test in hereditary MCT.

A new calcitonin (CT) immunoradiometric assay, using anti-11-7 and anti-24-32 CT fragment monoclonal antibodies was evaluated and compared to classical RIA. The sensitivity was 2.5 ng/L, the normal basal level (n = 83) was lower than 10 ng/L, the response to pentagastrin stimulation in control subjects was absent in nine and between 10-30 ng/L in nine others. (mean, 15.4). In patients with renal failure the basal level was increased between 10-52 ng/L. In patients with medullary thyroid carcinoma (MTC; n = 28), the basal level was between 189-28,900 ng/L. A pentagastrin test was performed as screening for familial MTC in eight patients with confirmed MTC at subsequent surgery; the calcitonin peak was equal or greater than 38 ng/L. Large differences exist between CT levels measured by RIA and immunoradiometric assay. The latter method provides a greater sensitivity to pentagastrin test and allows a better identification of microcarcinoma in hereditary cases of MTC.

Therapeutic effectiveness of iodine-131 MIBG metastases of a nonsecreting paraganglioma.

This case report describes the treatment of the bone metastases of a nonfunctioning sympathetic paraganglioma, with [131I]MIBG. After primary tumor excision and unsuccessful external radiotherapy, the patient received three therapeutic doses of [131I]MIBG, resulting in a reduction of the number and volume of metastases, and an improvement of the general condition. At 3 yr following [131I]MIBG therapy, the patient remained in remission. [131I]MIBG appears to be an efficient and safe agent for treating malignant sympathetic paraganglioma.

Scintigraphy with J001 macrophage targeting glycolipopeptide. A new approach for sarcoidosis imaging.

Scintigraphy with radiolabeled J001 as a ligand for macrophage targeting is a new approach for sarcoidosis imaging. J001 is a fully characterized acylated peptido-poly (1,3) galactoside isolated from Klebsiella membrane proteoglycans and able to bind electively recruited macrophages. Its physiochemical properties allow rapid absorption by the respiratory tract when this agent, labeled by 99m technetium, is administered as an aerosol. Images are obtained within 3 to 5 h after inhalation. In the present study, we determined the ability of J001 scintigraphy to localize areas of sarcoidosis involvement in 22 patients compared with gallium scanning in ten of them. Nineteen patients underwent bronchoalveolar lavage (BAL) and serum angiotensin-converting enzyme (ACE) assay. J001 scintigraphy was also performed on a control group of six patients with extrathoracic melanoma, in whom J001 scintigraphy was used to evaluate the cutaneous extent of the tumor and the lymph node involvement. In this control group, no fixation appeared in the thoracic area. In the sarcoidosis group, 18 positive results were observed. One stage 0 patient had a mediastinal fixation. Five of the six stage 1 patients had a fixation located in the mediastinum, the lungs, and the wrists. Five of the six stage 2 patients had positive foci located in the mediastinum or the lung areas and in the myocardium in one of them. Six of the nine stage 3 patients had positive J001 scintigraphy occurring in the lungs and/or the mediastinum. One patient had a fixation on the main bronchi. J001 scintigraphy and gallium scanning, performed in ten patients, were positive in seven of them. There were discrepancies between the BAL results and J001 scintigraphy, as well as between the ACE results and J001 scintigraphy. In conclusion, 99mTc-J001 scintigraphy appears to be a sensitive and rapid technique for the imaging of thoracic sarcoidosis at the three stages of the disease.

Iododerivative of pargyline: a potential tracer for the exploration of monoamine oxidase sites by SPECT.

Monoamine oxidases are important in the regulation of monoaminergic neurotransmission. An increase in monoamine oxidase B (MAO B) has been observed in some neurodegenerative diseases, and therefore quantification of cerebral MAO B activity by SPECT would be useful for the diagnosis and therapeutic follow-up of these disorders. We have developed an iodinated derivative of pargyline, a selective inhibitor of MAO B, in order to explore this enzyme by SPECT. Stable bromo and iodo derivatives of pargyline were synthesized and chemically characterized. The radioiodinated ligand [125I]-2-iodopargyline was obtained with high specific activity from the bromo precursor by nucleophilic exchange. Affinity and selectivity of 2-iodopargyline were tested in vitro. Biodistribution study of [125I]-2-iodopargyline was performed in rats. Radioiodinated ligand were obtained in a no-carrier-added form. 2-iodopargyline has a higher in vitro affinity for MAO B than pargyline. However, the in vitro selectivity for MAO B was better for pargyline than for 2-iodopargyline. Ex vivo autoradiographic studies and in vivo saturation studies with selective inhibitors of MAO showed that the cerebral biodistribution of [125I]-2-iodopargyline in the rat is consistent with high level binding to MAO B sites in the pineal gland and in the thalamus. In conclusion, 2-iodopargyline preferentially binds in vivo to MAO B sites with high affinity. However, its selectivity for MAO B in rats is not very high, whereas this ligand binds to a lesser extent to MAO A. It will be then of great value to evaluate the specificity of 2-iodopargyline in humans. This new ligand labeled with 123I should therefore be a suitable tool for SPECT exploration of MAO B in the human brain.

Exploration of the dopamine transporter: in vitro and in vivo characterization of a high-affinity and high-specificity iodinated tropane derivative (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-m ethylph enyl)nortropane (PE2I).

For the diagnosis and follow-up of neurodegenerative diseases, many cocaine derivatives have been proposed as radioligands to explore the dopamine transporter. As none of them have all the criteria of specificity and kinetics for human use, we have developed a new derivative, (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-methy lphenyl)nortropane (PE2I), which displays promising properties. We report the characterization of PE2I in vitro on rat striatal membranes and in vivo in rats and in monkeys. PE2I had a high affinity (Kd = 0.09 +/- 0.01 nM) and high specificity for the dopamine transporter. In rats we observed a high accumulation in the striatum; by contrast, a very low fixation was measured in the cortex. Moreover, a preinjection of a saturating dose of GBR 12909 prevented the striatal accumulation of PE2I by 74%. These results confirmed the specificity of PE2I for the dopamine transporter. In vivo in monkeys, SPECT studies showed a high accumulation in striatum. Moreover, an equilibrium state was obtained 1 h after injection. PE2I seemed to be the most promising ligand for the dopamine transporter exploration by SPECT using a single-day protocol.

[131I]-TYR3-octreotide: clinical dosimetry and use for internal radiotherapy of metastatic paraganglioma and carcinoid tumors.

Dosimetry and therapeutic application of [(131)I]-Tyr3-octreotide were evaluated in three patients with metastatic paraganglioma and carcinoid tumor. The in vitro stability of [(131)I]-Tyr3-octreotide was verified. Tumor uptake and residence time were between 0.02 and 0.1% and 0.5 to 9.8 h, respectively. The calculated tumor radiation doses were between 0.105 and 0.696 mGy.MBq(-1). No intolerance or adverse effects were observed after the therapeutic doses (3.3-6.6 GBq). A partial tumor response was obtained in one patient and no response occurred in two patients.

Comparison of two radioiodinated ligands of dopamine D2 receptors in animal models: iodobenzamide and iodoethylspiperone.

Several iodinated compounds have been developed for in vivo exploration of dopamine D2 receptors by SPECT. It is of great value to understand if the same information could be obtained with different radioligands. For this purpose, we compared in vivo properties of two iodinated ligands, iodoethylspiperone (IES) and iodobenzamide (IBZM), using different pharmacological and lesioning treatments in rats. Cerebral biodistribution performed by ex vivo autoradiograms and dissection of brain areas showed that IES and IBZM bound specifically to D2 receptors since a pre-injection of haloperidol prevented accumulation of both ligands. In contrast, when haloperidol was injected after IES or IBZM, only IBZM was displaced from its binding sites. This could be explained partly by a process of dopamine-dependent internalization with IES. The response to striatal quinolinic acid infusion for lesioning post-synaptic neurons was very different for IES and IBZM. In this model a decrease in IBZM accumulation occurred, corresponding to the loss of D2 receptors located on post-synaptic neurons. In contrast, a unexpected increase in IES accumulation was observed on the lesioned side. From these results we concluded that IES and IBZM, two iodinated ligands belonging to different pharmacological families, bound specifically to dopamine D2 receptors. However they have different properties in animal models. Therefore, it appears that IBZM is a more suitable ligand than IES to detect modifications of D2 receptors by in vivo exploration.

Iodobenzamide for in vivo exploration of central dopamine receptors: evaluation in animal models of supersensitivity.

Iodobenzamide is a promising agent to investigate D2 receptors by SPECT in living human brain. In this work, we have evaluated this radiolabeled compound in two animal models of D2 receptors supersensitivity. In the first model, rats were treated chronically with haloperidol during three weeks (S.C. injection of 0.5 mg/kg/day). One week after the last day of treatment, they were I.V. injected with 125I-IBZM. In vivo specific binding study showed a 45 percent increase of 125I-IBZM fixation in the striatum of treated rats. In a second step of experiments, animals were unilaterally lesioned by a stereotaxic injection of 6-OHDA in the substantia nigra, 23 days before receiving 125I-IBZM. Autoradiographic analysis of coronal brain sections showed a 38 percent enhancement of 125I-IBZM in vivo binding in the striatum on the lesioned side as compared to the contralateral intact side; this increase occurred in striatal lateral area. These data demonstrate that 125I-IBZM is convenient to detect alterations of dopamine D2 receptors in vivo in the rat. Thus IBZM labelled with 123I can be a very useful imaging agent for the exploration of D2 receptors in pathological situations.

[Plasma calcitonin and breast tumors]. / Calcitonine plasmatique et tumeurs mammaires.

In order to evaluate the frequency of elevated circulating calcitonin in patients with bone metastasis plasma calcitonin level was measured in 32 patients with breast carcinoma with and without bone metastasis. Calcitonin was found in normal ranges in all patients without metastasis. In patients with bone metastasis, 4 had normal level, 2 were found with elevated calcitonin. Our results suggest that elevated calcitonin is related to the presence of bone metastasis but is not a constant finding in these patients.

An original method for submacroscopic metastases visualization in cases of cancer minimal residual disease.

Scintigraphic imaging due to its sensitivity is in many cases one of the most powerful techniques for demonstrating metastases. Severe limitations still exist in cancer when it is necessary to detect the presence of a few tumour cells in the residual minimal disease. In preliminary experiments it had been observed that an immunomodulator isolated from Nocardia bacteria (Nocardia Soluble Peptidoglycan Derivative: NSPD) electively bound to a model of activated macrophages. An hypothesis has been put forward that the enhanced detection of macrophages that are usually present in the vicinity or inside tumours should represent a polyspecific test for scintigraphy of a variety of metastases. NSPD radiolabelled with 99mTechnetium is not usable when injected intravenously due to its physiochemical properties. It has therefore been encapsulated into liposomes then administered via the respiratory tract as an aerosol. Amphiphilic properties, as well as its low molecular weight allow a rapid diffusion of NSPD in blood. Scintigraphy of metastases was possible from 1.5 to 6 hours after inhalation. The first stage of the study was carried out on 5 patients bearing known metastases (skin, lymph nodes, bone) from malignant melanoma that all were imaged with 99mTc-NSPD. The test was then applied to patients with a high risk of recurrent cancers (melanoma: 6, breast tumour: 7) based on the detection in their plasmas of high Lipid Associated Sialic Acid (LASA) concentrations. The association of these two sensitive techniques has resulted in the detection of very small metastases that were not seen using conventional scintigraphy; they were then confirmed histologically.

Technetium-99m ECD single photon emission computed tomography in brain trauma: comparison of early scintigraphic findings with long-term neuropsychological outcome.

OBJECTIVE: The aim of this study was to assess the prognostic value of early brain scintigraphy in head injury in relation to long-term neuropsychological behavior. Twenty-four patients underwent technetium-99m (Tc-99m) ethyl cysteinate dimer single photon emission computed tomography (SPECT) within 1 month of the trauma. Scintigraphic abnormalities were evaluated both visually and semiquantitatively using the brain-to-cerebellum ratio method. The clinical neuropsychological investigation was conducted to evaluate abnormalities related to motor deficit, frontal behavior, and memory and language disorders. All patients had abnormalities on SPECT scan. One year after trauma, 14 patients (58%) had neuropsychological sequelae. The brain-to-cerebellum ratios in the left basal ganglia and brain stem were significantly decreased in patients with memory disorders (P = .03 and P = .02, respectively). Moreover, SPECT visual analysis indicated that low uptake in the basal ganglia, thalamus, and brain stem was associated with subsequent motor deficit, frontal behavior, and language and memory disorders. The authors conclude that brain SPECT can be valuable in predicting the neuropsychological behavior of survivors of severe head injury.

Scintigraphy in duodeno-gastric reflux: a new method of quantification.

A prospective study is undertaken in order to demonstrate the ability of scintigraphy with a non compartmental analysis to quantitate the duodeno-gastric reflux. 24 patients have been examined, sitting in front of a gamma camera: 12 with an endoscopically proved reflux and 12 normal subjects or volunteers. About 15 min after an injection of 148 to 222 MBq 99Tcm-IDA they were given a meal labelled with 37 MBq 113Inm-DTPA. Images were recorded for 2 h. Equal size gastric and duodenal ROIs were selected over the duodenum and stomach, avoiding overlap with neighbouring organs. The reflux index based upon the occupancy principle is calculated from the gastric and duodenal curves. It is the ratio between the gastric and duodenal ROI IDA fluxes. The value of the reflux index is 3 +/- 1.8% in normal subjects and 45 +/- 33% in pathological cases. Our method, which does not require intubation, quantitatively evaluates biliary reflux independently of injected dose and hepatic or gallbladder function.

Factorial analysis of dynamic lymphoscintigraphy in lower limb lymphoedema.

The purpose of this work is to assess the contribution of factor analysis to the interpretation of dynamic lymphoscintigraphy. Twenty six adult patients with a lower limb lymphoedema and five control patients were studied. The technique involved a 3 mCi lymphovectoscint* 99Tcm-labelled ammonium sulphur colloid, bilateral pedal subcutaneous injection. Recording consisted of 40 consecutive 1-min frames of both legs followed by static pictures of each leg and pelvis at 40 min and 4 h after injection. The analysis of static pictures allowed a classification of patients into three groups: enhanced pattern, hypoplasia and dermic reflux. To evaluate better the different kinetic components of the sequential pictures, a factorial analysis (FA) software package was used. FA processing enabled the extraction from the dynamic series of different dynamic components, factorial curves and their associated factorial images which represent the anatomic structures with the same temporal behaviour. In each pattern the results of dynamic recording and of three FA factors were compared. FA provides an analytical temporal and spatial description of the dynamic sequence by extracting the different kinetic components; it yields a better differentiation of vessel and interstitium activity. It also provides some clues towards the understanding of oedema physiopathology and is of potential interest for the management of lymphoedema.

The value of immunoscintigraphy in the detection of recurrent colorectal cancer.

The aim of this prospective study was to determine whether anti-carcinoembryonic antigen (anti-CEA) scintigraphy is a useful additional technique in the diagnosis recurrence of colorectal cancer. Forty patients with suspected recurrence of colorectal cancer, underwent immunoscintigraphy (IS) and helical computed tomography (CT) in the 2 weeks before surgery. Surgical findings were used to evaluate the performance of the imaging techniques. Suspected areas on IS and CT were systematically explored. Helical CT was found to be superior to IS for the liver, the sensitivity and specificity of CT being 100% and 90%, respectively, vs 53% and 100% for IS. However, IS was better than CT for the detection of extra-hepatic abdominal recurrence: sensitivity and specificity of IS were 100 and 82% respectively vs 33 and 82% for CT. Seven cases of peritoneal carcinomatosis were overlooked by helical CT. Our results indicate that IS improves detection of extra-hepatic abdominal recurrence of colorectal cancer. Immunoscintigraphy is valuable as a guide to the treatment strategy and operative procedures.

Effects of the method of drawing regions of interest on the differential diagnosis of extrapyramidal syndromes using 123I-iodolisuride SPET.

Various parameters are currently used for the semi-quantitative assessment of dopamine D2 receptors and differ according to the delineation of the striatal region of interest (ROI) and the choice of the reference ROI. The aim of this study was to assess the value of different ROI approaches in differentiating patients with normal or increased numbers of D2 dopamine receptors (group 1 = Parkinson's disease, n = 8) from patients with decreased dopamine D2 receptors (group 2 = other extrapyramidal syndromes, n = 9) using 123I-iodolisuride SPET (ILIS-SPET). 123I-iodolisuride (190 +/- 31 MBq) and 99Tcm-ethyl cysteinate dimer (99Tcm-ECD) perfusion SPET were performed in the same position, with a dual-headed gamera camera equipped with fan beam collimators. Both a geometric approach (ellipse, circle or rectangle) and an anatomical approach using the CT scan and perfusion SPET as anatomical guides were used to draw striatal and reference ROIs. A total of 33 different parameters were calculated for each patient, indicating the ratio of counts between the striatal and reference ROIs (frontal, occipital cortex or cerebellum) and the asymmetry between the right and left striatum. More significant differences between group 1 and group 2 were found by using geometric ROIs than by using anatomical ROIs. The most discriminant ratios were the caudate/occipital, caudate/frontal and striatum/occipital ratios (P = 0.001, P = 0.002, P = 0.003 respectively). A close correlation was found between the striatum/caudate and striatum/occipital ratios, but not between the striatum/frontal and striatum/occipital ratios or between the striatum/frontal and striatum/caudate ratios. We conclude that the occipital cortex is the best reference for the semi-quantitative evaluation of dopamine D2 receptors as the frontal cortex could include some dopamine D2 receptor-bound radioligand, and that the caudate/occipital ratio is an appropriate parameter for differentiating Parkinson's disease from non-Parkinson extrapyramidal syndrome by 123I-iodolisuride SPET.

Quantitative analysis of striatal dopamine D2 receptors with 123 I-iodolisuride SPECT in degenerative extrapyramidal diseases.

123I-Iodolisuride has high specific affinity for binding on dopamine D2 receptors in the striatum and has been used in a few single photon emission computed tomography (SPECT) studies of extrapyramidal disorders. The diagnosis of Parkinson's disease (PD) is very difficult in the first 5 years of evolution, with 15-25% false positive diagnoses. The aim of this study was therefore to determine the value of iodolisuride SPECT in discriminating Parkinson's from the most frequent Parkinson-plus syndromes (PPS). Seventeen patients with an extrapyramidal syndrome had a SPECT examination 1 h after injection of 180-185 MBq of 123I-iodolisuride. They were followed under dopaminergic treatment for at least 2 years. After 2 years, they were separated in two groups according to specific clinical criteria and sensitivity to dopaminergic treatment: nine patients had PD (age = 59.8+/-8.8 years; Hoehn and Yahr = 1.8+/-0.7; evolution = 4.3+/-3 years) and eight had PPS (age = 71.6+/-7.3 years; Hoehn and Yahr = 2.9+/-2.0; evolution = 4.1+/-1.5 years). The binding potential of iodolisuride in the striatum was assessed by considering the striatum (S)/occipital lobe (O) ratio at the pseudo-equilibrium 1 h after injection. The S/O ratio was statistically different between PD and PPS (1.97+/-0.3 vs. 1.65+/-0.2 (P<0.02)). Iodolisuride SPECT could differentiate both groups with a sensitivity of 88.8% and a specificity of 75%. Iodolisuride is a good specific D2 receptor ligand for SPECT and complements specific clinical criteria for the diagnosis of Parkinson's disease and differentiation between different extrapyramidal disorders.

[Imaging medullary cancer of the thyroid]. / Imagerie du cancer médullaire de la thyroïde.

Based on experience of the last decade including 18 patients, the imaging procedures of medullary thyroïd carcinoma are reviewed. Ultrasonography of the neck is the most contributive for the locoregional expertise, in the preoperative period. All of the classical imaging procedures are useful in looking for the metastasis: namely bone scintiscan, liver ultrasonography, computerized tomography of the mediastinum. Associated parathyroid adenoma and pheochromocytoma are visualized respectively by technetium thallium subtraction scan and meta-iodobenzylguanidine scintigraphy. In the near future, immunoscintigraphy of calcitonin secreting tumors will be developed.

Use of lymphscintigraphy in traumatic chylous ascites.

This report describes the use of lymphscintigraphy in a patient with traumatic chylous ascites. Radioactivity "leakage" near the origin of the thoracic duct and accumulation into the peritoneal cavity were delineated.

Factorial analysis in radionuclide lymphography: assessment of the effects of sequential pneumatic compression.

The effects of intermittent pneumatic compression (IPC) in 12 patients with lower or upper limb lymphedema were studied using a computer-based technique (factorial analysis) of dynamic lymphoscintigraphy. After subcutaneous injection of radiocolloid into the first interdigital web space of the arm or leg, scintigraphic recordings consisted of 40 consecutive one-minute frames of both lower extremities or an edematous upper extremity. Pneumatic compression by Euroduc (6 patients) or by Lymphapress (6 patients) was applied during the final 20 minutes of the recording. A three factors factorial analysis (FA) was performed successively for each extremity. FA allowed "uncontaminated" curves to be displayed distinct from neighboring structures and corresponded to dynamic tracer activity in the interstitium, at the injection site, and within lymphatic vessels. Based on the results of lymphatic vascular factorial analysis, a beneficial effect of IPC was detected in 18 of 22 limbs examined. FA processing suggested that IPC facilitated radiocolloid transport in the proximal portion of the limb and also propelled tracer from the injection site toward the lymphatics. The effect of IPC was evident as soon as external compression therapy began and was similar with either mechanical unit. Residual tracer activity in peripheral lymphatics 20 minutes after application of IPC was higher in the edematous as compared with the normal limbs. FA processing is a new and potentially valuable method to evaluate the effects of external pneumatic compression in the management of peripheral lymphedema.

The potential usefulness of condensed image processing of sequential lymphoscintigrams in patients with lymphedema.

Condensed image processing (CIP), a computerized technique of scintiscans that generates a vertical distribution of activity as a function of time in a single image, was applied to isotopic lymphoscintigrams of four patients with leg lymphedema. By "condensing" information gained from multiple images into a single image, CIP better evaluates ascending progression of radiolabeled colloid in peripheral lymph and better localizes stagnant areas. In "high lymph flow failure," CIP also depicts radioactive "bursts" suggestive of increased lymphatic truncal contractility. This data processing method improves interpretation of dynamic scintiscan recordings and seems ideally suited for evaluation of peripheral lymph kinetics.