In vivo experimental imaging of osteochondral defects and their healing using (99m)Tc-NTP 15-5 radiotracer.

PURPOSE: A rabbit model of osteochondral defects (OD) and spontaneous healing was longitudinally followed over 12 weeks, by in vivo joint scintigraphy using (99m)Tc-NTP 15-5, and histology. METHODS: We used two models, one with one OD (OD1 group) in the femoral condyle of one knee and the other with two ODs (OD2 group) in the femoral condyle of one knee, with the contralateral knees serving as the reference. A serial longitudinal imaging study was performed with the scintigraphic ratio (SR, operated knee uptake/contralateral knee uptake) determined at each time-point. RESULTS: ODs were imaged as radioactive defects. The SR was decreased with respective to controls, with values of 0.73 ± 0.08 and 0.65 ± 0.07 in the OD1 and OD2 groups, respectively, at 4 weeks after surgery. Histology of both OD groups revealed the presence of repair tissue characterized by a small amount of sulphated glycosaminoglycans and collagen. CONCLUSION: (99m)Tc-NTP 15-5 imaging provided quantitative criteria useful for in vivo evaluation of cartilage trauma and healing.

A starch-based microparticulate system dedicated to diagnostic and therapeutic nuclear medicine applications.

The aim of this work was to develop a new microparticulate system able to form a complex with radionuclides with a high yield of purity for diagnostic or therapeutic applications. Owing to its properties potato starch was chosen as starting material and modified by oxidization and coupling of a ligand (polyamine) enabling modified starch to chelate radionuclides. The choice of suitable experiments was based on a combination of a Rechtschaffner experimental design and a surface response design to determine the influence of experimental parameters and to optimize the final product. Starch-based microparticle formulations from the experimental plans were compared and characterized through particle size analysis, scanning electron microscopy, elemental analysis and, for the most promising formulations, by in vitro labeling stability studies and determination of free polyamine content or in vivo imaging studies. The mechanism of starch-based microparticle degradation was identified by means of size measurements. The results of the Rechtschaffner design showed the positive qualitative effect of the temperature and the duration of coupling reaction whereas surface response analysis clearly showed that, by increasing the oxidization level and starch concentration, the nitrogen content in the final product is increased. In vitro and in vivo characterization led to identification of the best formulation. With a size around 30 µm, high radiochemical purity (over 95%) and a high signal-to-noise ratio (over 600), the new starch-based microparticulate system could be prepared as ready-to-use kits and sterilized without modification of its characteristics, and thus meet the requirement for in vivo diagnostic and therapeutic applications.

Pathology underrates colon cancer extranodal and nodal metastases; ex vivo radioimmunodetection helps staging.

PURPOSE: Colorectal carcinoma is frequently accompanied by small lymph nodes metastases that often escape pathologic examination. We evaluated whether ex vivo radioimmunodetection with the Affinity Enhancement System (AES) could improve detection of mesocolonic metastases. EXPERIMENTAL DESIGN: A bivalent 111In-labeled hapten was injected (16 patients) 4 days after a bispecific antibody (anticarcinoembryonic antigen, antihapten). Surgery was done 1 to 3 days later, and radioactive uptake in the mesocolon was recorded. Extensive pathologic examination of the mesocolon (reference method) was done after fat dissolution. This method visualizes all lymph nodes but is not in routine use. RESULTS: The reference method disclosed 705 nodes. There was no significant difference between the number of node metastases detected by AES or by the reference method (16 versus 17). Better detection would have been obtained by AES than by routine pathology (P<0.01). In addition 12 extranodal metastases were found in this study of which eight were detected by AES. The prognostic importance of such extranodal metastases has been underlined in the literature. Routine pathology combined with AES would have disclosed all node metastases and 86% of total metastases versus 35% by routine pathology alone. CONCLUSIONS: Ex vivo radioimmunodetection could improve nodal and extranodal metastases detection in patients with colorectal cancer. Its value for improving pathologic analysis, together with the effect of these small metastases on prognosis, should be further evaluated. The benefit of adjuvant chemotherapy for patients upstaged with radioimmunodection should also be assessed because adjuvant chemotherapy improves the 5-year survival of stage III patients.

Successful surgical removal of occult metastases of medullary thyroid carcinoma recurrences with the help of immunoscintigraphy and radioimmunoguided surgery.

Patients with recurrent or metastatic medullary thyroid carcinoma (MTC) were referred for pretargeted immunoscintigraphy (Affinity Enhancement System; AES) and radioimmunoguided surgery (RIGS). Data collected from 13 patients establish that whole-body AES immunoscintigraphy revealed metastases < 360 mg and RIGS detected micrometastases (5-15 mg). All tissue samples removed by the surgeon were diagnosed by histology and immunohistochemistry of calcitonin to check the accuracy of IS and RIGS results. AES immunoscintigraphy is very sensitive. Of 34 metastases or recurrences detected, 22 had escaped physical examination or conventional imaging. The accuracy of RIGS was 86%, its sensitivity 75%, and its specificity was 90% (n = 208). IS and RIGS detected occult tumors that would have escaped surgery, clearly demonstrating clinical benefit. Serum calcitonin (normal, 10 pg/ml) and carcinoembryonic antigen (normal, 5 ng/ml) of two patients were restored to normal. In patients whose tumors were discovered, progression of their disease was slowed, as evidenced by the large decrease in serum calcitonin and carcinoembryonic antigen, an important prognostic factor. Surgery was canceled in one case where IS detected distant metastases out of surgical reach. Thus, AES immunoscintigraphy and RIGS might be of valuable help for the surgical management of medullary thyroid carcinoma.

The practice of nuclear medicine in common market countries.

There is no politically structured European policy on nuclear medicine, and there are significant discrepancies between the various member states. It is hard to guess whether competing imaging modalities will slow down the process of development that took place in underequipped countries. But it appears likely that with the free circulation of professionals between European Community countries, free competition will stimulate these countries toward major development in nuclear medicine.

Multicentre evaluation of a two-step automated enzyme immunoassay of free thyroxine.

The two-step enzymatic immunoassay of free thyroxine (IMx FT4, Abbott Laboratories, Chicago, IL) was studied in three centres. The assay involved a fluorimetric measurement and took 45 minutes using a completely automated procedure. The results were compared with those from the free thyroxine two-step radioimmunoassay and with the "calculation" of free thyroxine. The analytical precision was found to be excellent if the analyser was correctly set. The IMx FT4 assay seemed unaffected by increased concentrations of albumin and of non-esterified fatty acids (oleic acid) up to 5 mmol/l. The euthyroid reference interval, defined as that including 95% of 194 control subjects, was 12-21 pmol/l. A limited overlap existed between euthyroid and hyperthyroid patients, but a larger one was seen between the euthyroid and hypothyroid population, the latter including subclinical hypothyroidism. IMx FT4 results agreed well when compared with those from two-step radioimmunoassays. The IMx FT4 technique gave rise to a low percentage of elevated results in patients being treated with heparin, but was undisturbed by autoantibodies to thyroxine and triiodothyronine which were present in one hypothyroid patient.

(99mTc)-HM-PAO SPECT and cognitive impairment in Parkinson's disease: a comparison with dementia of the Alzheimer type.

Regional cerebral perfusion was evaluated by single photon emission tomography (SPECT) using (99mTc)-HM-PAO as a tracer, in thirty Parkinsonian patients with (n = 15) or without (n = 15) dementia, nineteen patients with dementia of the Alzheimer type (DAT) and thirteen control subjects. HM-PAO uptake was measured in the frontal, parietal, temporal and occipital cortex and tracer perfusion was expressed as cortical/cerebellar activity ratios. Regional HM-PAO ratios in nondemented Parkinsonian patients did not differ from controls, whereas in demented patients with Parkinson's disease (DPD) a significant reduction was found in the parietal, temporal and occipital cortex. Tracer uptake ratios were significantly reduced in all regions in the DAT group. Thus DPD and DAT shared a common pattern of marked posterior hypoperfusion, although the perfusion defect was greater and more extensive in the DAT patients.

A comparative technetium 99m hexamethylpropylene amine oxime SPET study in different types of dementia.

Regional cerebral perfusion was evaluated by single photon emission computed tomography (SPET) using technetium 99m hexamethylpropylene amine oxime (99mTc-HMPAO) as a tracer, in 13 control subjects and 44 age-matched patients suffering from dementia of the Alzheimer's type (DAT, n = 19), presumed Pick's disease (n = 5), idiopathic Parkinson's disease with dementia (DPD, n = 15) and progressive supranuclear palsy (PSP, n = 5). HMPAO uptake was measured in the superior frontal, inferior frontal, parietal, temporal and occipital cortices, and the perfusion values were expressed as cortical/cerebellar activity ratios. As compared with controls, tracer uptake ratios in the DAT group were significantly reduced over all cortical regions, with the largest defects in the parieto-temporal and superior frontal cortices. A marked hypoperfusion affecting the superior and inferior frontal cortices was found in Pick's disease, whereas a mild but significant hypoperfusion was observed only in the superior frontal cortex of patients with PSP. In the DPD group, HMPAO uptake was significantly reduced in the parietal, temporal and occipital cortices, but not in the frontal cortex. These results show that DAT and DPD share an opposite anteroposterior HMPAO uptake defect as compared with the Pick's and PSP groups.

Validation of diagnostic procedures on stratified populations: application on the quantification of thallium myocardial perfusion scintigraphy.

In this report we present a method for the quantitative description of the degree of deviation from the norm of 201thallium single photon emission tomographic (SPECT) data. Validation is obtained from the frequency of "positive" outcomes in subgroup of patients in whom the prevalence of coronary artery disease, for the group as a whole, is known, even if individual patient outcomes are not verified. This approach overcomes the bias associated with nonrandomized clinical studies, in which the likelihood that a more invasive but definitive procedure (coronary arteriogram) will be performed is influenced by the result of the outcome of the procedure under study.

Lack of correlation between DST results and urinary MHPG in depressed inpatients.

Abnormalities of noradrenaline metabolism and of the activity of hypothalamic-pituitary adrenal axis (HPA) have been reported in depression. To study the possible relationship between these 2 parameters, urinary excretion of 3-methoxy-4-hydroxy-phenylethyleneglycol (MHPG) and Dexamethasone Suppression Test (DST) were analyzed in 58 depressed patients. A positive correlation was found between the age of depressed patients and 24-h urinary excretion of MHPG. Twenty-two patients (38%) were DST non suppressors. Pre-DST plasma cortisol levels were significantly higher in non suppressors than suppressors. No difference was found however between urinary MHPG levels in suppressors and non suppressors. There was no correlation between pre-DST plasma cortisol and levels of urinary excretion of MHPG. These results do not support the hypothesis of a relationship between these 2 parameters. However, when depressed patients were separated into two groups according to urinary excretion of MHPG ("high MHPG" and "low MHPG"), the "high MHPG" group included significantly more non suppressors then the "low MHPG" one. This result is not sufficient to demonstrate of link between HPA system activity and central noradrenaline metabolism.

Clinical significance of a low concentration of thyrotropin: five immunometric "kit" assays compared.

We compared results of five sensitive immunometric assays of serum thyrotropin (TSH) in controls and in different groups of patients with hyperthyroidism, untreated or treated; secondary hypothyroidism; nonthyroidal illness (NTI); or depression; or who were being treated with amiodarone. With most kits, measured TSH concentrations did not overlap between controls and hyperthyroid patients. In untreated secondary hypothyroidism TSH was not always undetectable. Patients with NTI and depression showed many low TSH values, and among these categories of patients, we observed large discrepancies among the kits. This lack of specificity at low concentration means that one cannot assess hyperthyroidism by TSH measurement alone, but it can be used as the first screening test. Similarly, TSH determination cannot be used alone in monitoring therapy (e.g., with carbimazole, thyroxin, amiodarone) to assess the presence of hyperthyroidism. Nonetheless, this assay plays a well-established role in hypothyroidism detection. Four of the five kits were found useful for clinical evaluation, the fifth less so.

Platelet MAO activity in clinical subtypes of depression and DST suppression.

Platelet MAO activity was measured in 75 hospitalized depressed patients and in 31 healthy subjects. Plasmas post dexamethasone cortisol levels were examined in 73 patients. Results indicate that higher platelet MAO activity does not occur in all, but only in male major depressed patients. No relationship between changes of MAO activity and specific clinical subtypes was found. Platelet MAO activity is not different between DST suppressors and DST non suppressors. The authors suggest that platelet MAO activity may be related to non specific factors such as sex, age, but not to diagnosis of depression.

Plasma 3,4-dihydroxyphenylethyleneglycol levels in depressed patients with and without abnormal dexamethasone suppression.

Escape from dexamethasone-induced suppression of plasma cortisol is an abnormality found in about half of patients with major depression. It has been hypothesized that this hyperactivity of the hypothalamo-pituitary-adrenal axis might be related to a central noradrenergic hypofunction. The present study was designed to test this hypothesis by measuring plasma 3,4-dihydroxyphenylethyleneglycol (DOPEG) levels (free and conjugated forms), an index of central noradrenergic activity, and by simultaneously carrying out a dexamethasone suppression test. Forty-five patients with a diagnosis of major depression (according to the DSM-III) were investigated. Plasma DOPEG levels (measured at 8 a.m.) were found to be similar in dexamethasone suppressor and nonsuppressor depressed patients. These results do not support the hypothesis that central noradrenergic hypoactivity underlies nonsuppression of dexamethasone in major depression.

[Stereotaxic treatment of expanding cysts in craniopharyngiomas by endocavitary beta-irradiation (Re-186; Au-198; Y-90)]. / Traitement stéréotaxique des kystes expansifs de crânio-pharyngiomes par irradiation endocavitaire bêta (Re 186; Au 198; Y 90).

The authors report the results of 17 intracystic injection of colloidal 186 rhenium, 2 colloidal 198 gold, and 1 colloidal 90 yttrium for endocavitary treatment of 18 cystic craniopharyngiomas (16 pts during a period ranging from January 1975 till July 1982. Follow-up studies ranging from 12 to 72 months (m: 36 m) revealed that all craniopharyngiomas cysts were effectively treated with cessation of fluid formation, progressive shrinkage of the formerly expansive cysts, and finally cyst obliteration in 75% of the cases. No early or late side-effects were observed during the entire observation period. Late reexpansion of one craniopharyngioma cyst, observed at 11 months, was successfully treated by a second injection. Leakage of colloid isotope into the CSF spaces during the "test" or "therapeutic" injections occurred in 18% of the global number of injections, however no clinical complications were observed. On the basis of a clinical dosimetric study a 30 000 rads wall-dose, not exceeding 40 000 rads is actually considered as the safer dose for endocavitary treatment of craniopharyngioma.

[Contribution of iodinated cisternography to craniocerebral computed tomography]. / Apport de la cisternographie iodée à la tomodensitométrie cranio-cérébrale.

Computerized tomography is usually adequate to explore supratentorial lesions of the skull and brain. However, it is often inadequate for a detailed analysis of lesions of the base of the skull and their anatomical rapports. Opacification of the subarachnoid spaces by means of a contrast medium (computerized cisternography) has proved extremely useful in such cases. The contrast media utilized are tri-iodized, water-soluble compounds which are well tolerated. The technique and anatomical data of the method are described, and its applications in different fields of tumoral and non-tumoral pathology are discussed.

[Neuroradiological examinations in psychiatry]. / Explorations neuroradiologiques en psychiatrie.

The search for an organic etiology in psychiatric conditions is greatly facilitated by modern radiological techniques. The most frequent etiologies demonstrated in the department of Radiology at the Sainte Anne Hospital were tumors, dementias, vascular disease and trauma with its attendant pathology.

[Chemical and pharmacological aspects of cerebral cellular tracers]. / Aspects chimique et pharmacologique des traceurs cellulaires cérébraux.

Among the iodophenylalkylamines studied and labelled with iodine 125 or iodine 123, N-isopropyl-iodo-amphetamin (IAMP) was selected and proposed as tracer for blood flow, a "chemical embolus" having almost 100% extraction in the brain. A new way of obtaining N-isopropyl-p-iodo-amphetamin is proposed and the easily-applied exchange reaction with iodine 125 or 123 gives a product with a radiochemical purity of more than 96% and an unexchanged radioactive iodine content of less than 1%. The pharmacokinetic study of this product in the Wistar rat showed distribution in three compartments and the appearance of a steady state by the fourth minute. The target organs are the lungs, liver and brain. The latter receives 3% of the radioactivity and the autoradiographic study shows that the early distribution in the brain for IAMP closely equals the blood flow as found by a diffusible indicator. In the first hour, the redistribution is very low and at this time although IAMP is proposed for the study of regional blood flow, it does not exactly determine the flow but rather mirrors cell activity.