Age-dependent enzymuria, proteinuria and changes in renal blood flow and glomerular filtration rate in rats.

The time course of urinary excretion of two enzymatic indicators of renal damage, N-acetyl-beta-D-glucosaminidase (NAG) and alanine aminopeptidase (AAP) was measured in female Wistar rats at different ages. NAG and AAP are localized at different sites of the nephron and are released into the urine when kidney damage occurs. Total protein flow, urinary volume and creatinine flow were also determined. In a parallel experiment, the effect of aging on renal blood flow (RBF) and glomerular filtration rate (GFR) was examined in young (1.5-month) adult (3-month) and elderly (20-month) female rats. Clearance following a single injection of [131I]o-iodohippurate (hippuran, OIH) was used for the measurement of effective RBF and as an index of tubular cell function. [125I]Iothalamate (IOT) clearance was used to measure GFR. With advancing age, an increase in NAG and AAP urinary flow appeared. The increases in protein excretion were greater than and previous to those of enzyme excretion. It is shown that absolute RBF and GFR (ml/min) in old rats are greater than in young or adult animals. When absolute RBF or GFR was divided by kidney weight (ml/min/g) no clearance changes appeared in any age group studied; only when clearance was expressed in relation to body weight (ml/min/100 g), a decrease in RBF and GFR was evidenced. This indicates that the rate of increase of both RBF and GFR with age is similar to that of kidney weight and lower than that of body weight. The present findings indicate that urinary markers of renal injury increase with age, whereas GFR and RBF only decrease when expressed as clearance related to body weight.

The usefulness of 111In-labeled platelet scintigraphy in the diagnosis of patients with febrile syndrome and a nonfunctioning renal graft.

111In-labeled platelet scintigraphy was used to confirm immunological intolerance as the cause of prolonged febrile syndrome in hemodialyzed patients with a nonfunctioning renal allograft. Thirty-six patients with febrile syndrome (> 38 degrees C) and a nonfunctioning renal graft were studied. Thirteen patients were under minimal steroids (5-10 mg/day) and 23 were free of immunosuppressive therapy. A control group of 6 patients without fever and with a nonfunctioning renal graft was also included. The labeling of autologous platelets with 111In-mercaptopyridine was performed following a modified technique of Thakur. Scans were obtained at 24 and 48 hr after injection of 100-200 microCi of 111In-labeled platelets. A platelet uptake index (PUI) was calculated to evaluate the results of the scintigraphy. A PUI > 1.5 at 24 or 48 hr was considered positive and suggestive of immunological activity in the nonfunctioning renal allograft. In the study group the PUI was considered positive in 26 patients and negative in 10. In 3 patients with positive PUI, fever disappeared after steroid treatment, and transplantectomy was performed in the remaining 23. In 8 of the 10 patients with a negative PUI, fever disappeared with antimicrobial therapy. In the control group, a negative PUI was obtained in all cases. The sensitivity of PUI in demonstrating immunological intolerance of the nonfunctioning renal allograft was 93% with a specificity of 100%. Our results suggest that this new approach with 111In-labeled platelet scintigraphy may constitute a good marker for discriminating the origin of the febrile syndrome in patients with a nonfunctioning renal allograft. A positive PUI (> 1.5) strongly suggested immunological intolerance of the nonfunctioning allograft.

Hyperperfusion and early technetium-99m-HMPAO SPECT appearance of central nervous system toxoplasmosis.

Three correlative 99mTc-HMPAO brain SPECT studies were performed on an AIDS patient from the early stage of a CNS toxoplasma lesion to its resolution after specific therapy. A hyperactive area in the right parieto-occipital lobe appeared in the first SPECT study, matching the heterogeneous T2-weighted image with Gd-DTPA enhancement reported on MRI. Both studies were performed 3 days after the onset of neurological symptoms when no abnormalities were found on a CT scan. This fact can be explained by the hyperemia that occurs in the acute stage of inflammation. Three months later, along with clinical improvement under specific treatment, both MRI and brain SPECT were normal. No hypoperfusion was seen in SPECT images, probably because the necrotic phase of the toxoplasma lesion was not reached in this case.

Experimental study on radioactive pathways of hypodermically injected technetium-99m.

The objective of this study was to investigate the biological substrate of radioactive pathways of migration of hypodermically injected 99mTc into points of low electrical resistance. Sixteen anesthetized adult male beagles were used. Control and test points were defined by comparing their electrical resistance to that of the pinna. Seventy-three experiments of three different types were performed: (1) separate hypodermic injections of [99mTc] sodium pertechnetate, 201Tl-chloride, 131INa and 99mTc-rhenium sulfide into control and test points; (2) simultaneous injections of [99mTc]sodium pertechnetate and 201Tl chloride into control and test points; and (3) intravascular injections of 99mTcO4 into blood vessels underlying test points. Only the hypodermic injection of 99mTc into points of low electrical resistance gave rise to a specific radioactive pathway characterized by rapid and longitudinal migration, clearly independent of background activity. The specific radioactive pathway detected is not the result of diffusion of the radiotracer through nerves, veins or lymphatic vessels, but its trajectory coincides with that described for one of the acupuncture meridians in the dog.

Prefrontal and temporal blood flow in schizophrenia: resting and activation technetium-99m-HMPAO SPECT patterns in young neuroleptic-naive patients with acute disease.

UNLABELLED: This study assesses prefrontal and temporal regional cerebral blood flow (rCBF) changes in young, neuroleptic-naive schizophrenic patients with acute disease. METHODS: A selected population of 10 young, never-treated schizophrenic women with acute disease was studied by two hexamethylpropyleneamine oxime (HMPAO) brain SPECT sessions, performed 48 hr apart, both at rest and during a prefrontal activation task using the Wisconsin Card Sort Test (WCST). All patients met Diagnostic and Statistical Manual of Mental Disorders, 3rd edition-revised criteria for schizophrenia or schizophreniform disorder, were neuroleptic-naive and had acute symptoms. RESULTS: Under resting conditions, the schizophrenic group had significantly higher rCBF in the prefrontal regions, mainly in the left side and including the anterior cingulate, than did the controls. In addition, schizophrenic patients showed significant interhemispheric differences in prefrontal and posterior temporal index values at rest (left hyperfrontality and left hypotemporality). During WCST activation, the control group showed significant increases in prefrontal blood flow, whereas the schizophrenic group did not. CONCLUSION: These results support a physiologic dysfunction of the prefrontal cortex in schizophrenia that is present at the onset of the illness prior to neuroleptic treatment. Furthermore, both left hyperfrontality and left hypotemporality may indicate a brain lateralization defect in schizophrenia.

Procedure for red blood cell labelling with 99mTc-HMPAO. Methodology and quality control.

We present here results on the labelling of red blood cells with 99mTc-HMPAO as an alternative method to the usual in vitro technique. Anticoagulant agents, the labelling medium with plasma, and the lapse of time between 99mTc-HMPAO preparation and labelling are the main factors which affect the efficiency of the procedure. A 93.9 +/- 2.3% labelling yield was obtained with freshly prepared 99mTc-HMPAO. In vitro (tracer elution of 4.3 +/- 1.2% at 60 mins) and in vivo (percentage of plasma activity at 60 mins, 7.8 +/- 2.8%) stability of the label, as well as image quality, qualify 99mTc-HMPAO labelled red blood cells as a suitable agent for clinical use.

Nocturnal paroxysmal dystonia related to a prerolandic dysplasia.

Nocturnal paroxysmal dystonia (NPD) is a rare disorder characterized by attacks of short-lived dystonic, tonic and choreoatetoid movements occurring mainly during sleep. Although seizures are believed to arise from the frontal lobe, their localization is, however, uncertain due to the lack of ictal clinical-EEG correlations. Two patients are reported with episodes clinically compatible with NPD who also experienced occasional generalized tonic-clonic seizures in which there was a frontal (prerolandic) dysplasia detected by MRI. In one patient interictal/ictal SPECTs suggested that the seizure focus was over the area of dysplasia. Both patients support the notion that NPD is a type of epilepsy arising from the frontal lobe, possibly originating in the prerolandic region.

Prefrontal dysfunction in young acute neuroleptic-naive schizophrenic patients: a resting and activation SPECT study.

Regional cerebral blood flow (rCBF) was measured with single photon emission computed tomography (SPECT) in six neuroleptic-naive, young, acute schizophrenic patients and six normal control subjects. We evaluated rCBF changes in prefrontal areas at rest and during a prefrontal activation task, the Wisconsin Card Sorting Test (WCST). Schizophrenic patients had significantly higher prefrontal blood flow than did control subjects during the resting conditions. During activation, the control group showed significant increases in prefrontal blood flow, whereas the schizophrenic group did not. These results suggest that at rest there is no evidence of hypofrontality, whereas hyperfrontality seems to be the most frequent pattern in our selected sample of young acute neuroleptic-naive schizophrenic patients. Furthermore, schizophrenic patients seem to be unable to increase prefrontal blood flow under conditions that challenge the prefrontal cortex.

Role of the cingulate gyrus during the Wisconsin Card Sorting Test: a single photon emission computed tomography study in normal volunteers.

The purpose of this study was to investigate the effect of the Wisconsin Card Sorting Test (WCST) on frontal regional cerebral blood flow (rCBF) in normal subjects, separating the cingulate gyrus from the prefrontal cortex. Two technetium-99m-hexamethyl-propylene-amine-oxime brain single photon emission computed tomography (SPECT) scans, at rest and during WCST performance, were performed in randomized order on 13 right-handed normal volunteers. A statistically significant rCBF increase was found in the left inferior cingulate and the left posterior frontal region, although rCBF ratios in the left and right prefrontal cortex, and in the right inferior cingulate, were slightly higher during WCST performance in nine of the 13 subjects studied. No differences in activation scores (activated-resting rCBF ratios) were found between subjects who had the resting SPECT first and subjects who had the resting condition second. These results suggest that the inferior cingulate cortex, a limbic region that has been implicated in attentional mechanisms, plays a significant role in WCST performance. Furthermore, the motor component of the WCST may account for the activation of the left posterior frontal region. In addition, no order effect was found in this study. These findings illustrate the advantage of independently evaluating the cingulate gyrus and the prefrontal cortex in SPECT studies of frontal cognitive function.

Experiences in setting up the first centralized radiopharmacy in Spain.

The centralized radiopharmacy set up in Spain by the Cetir Medical Group allows optimal use of radiopharmaceuticals and complies with laws (Directive 89/343/EEC and Royal Decree 479/1993/Spain) governing their use. More than 220,000 individual patient doses have been supplied since the unit was established in November 1995. In this paper, we describe the infrastructure of the centralized radiopharmacy, including the operations and procedures involved, and how we believe we have achieved our original objectives.

Information as a fundamental attribute among outpatients attending the nuclear medicine service of a university hospital.

The aim of this study was to assess outpatients' satisfaction with the service received in the nuclear medicine service of the Hospital Clinic i Provincial of Barcelona in February 1993. The patients were randomly assigned to one of two groups: group 1 received information about their diagnostic procedure, whereas group 2 did not (a control group). A questionnaire was used to assess patients' degree of satisfaction. The questionnaire was administered to 803 patients, 243 (30.26%) of whom completed it and returned it. The following factors were significantly related to high scores on the satisfaction scale: age (P < 0.015), waiting time (P < 0.001), treatment by assisting personnel (P < 0.001), treatment by personnel at the service reception (P < 0.01), waiting room habitability (P < 0.01), communication variables (P < 0.03) and low scores on the anxiety scale (P < 0.02). Group 1 perceived more positively treatment by personnel at reception (P < 0.041), treatment by assisting personnel (P < 0.027), waiting room habitability (P < 0.035) and communication variables (P < 0.001). The anxiety scale scores among this group were significantly lower. We conclude that when information is supplied to patients, their anxiety decreases before a diagnostic procedure, which significantly improves their perception of the factors that generate satisfaction among patients.

Comparative study of the kinetics of the renal tracers 99Tcm-MAG3 and 131I-hippuran.

Serial measurements of plasma activity, plasma protein binding and urine excretion were obtained in order to study 99Tcm-MAG3 (MAG) and 131I-Hippuran (OIH) kinetics after simultaneous injection of both tracers in 21 patients with various renal diseases. Results were compared on the basis of a compartmental model, calculating the rate constants as well as the clearance and volume of distribution. Protein binding was calculated in 10 patients (mean: MAG = 54.7%, OIH = 33.8%). The dependence of time, tracer and patient factors was shown by ANOVA. Time was independent, with tracer and patient factors and their interaction being significant. The mean value of the renal excretion constant was equal for the two tracers (k12 = 0.052 min-1). The clearance values were found to be highly correlated (r = 0.982) with a ratio of 0.57 between them. The volumes of distribution in litres were 4.1 (MAG) and 7.0 (OIH). One-hour urine excretion was nearly the same for both tracers (MAG: 64%, OIH: 63% of the injected dose).

Baseline, visual deprivation and visual stimulation 99TCm-HMPAO-related changes in visual cortex can be detected with a single-head SPET system.

To determine the sensitivity of 99TCm-hexamethylpropylene amine oxime (99TCm-HMPAO) and a single-head SPET (single photon emission tomography) system in the detection of perfusion changes in the visual cortex due to different visual conditions, six normal healthy volunteers were studied under conditions of visual deprivation (blindfolded), visual stimulation (stroboscopic light) and baseline (dim light and eyes open). Visual cortex/whole-brain activity ratios, and the percentage of activity change between the different visual conditions were calculated after three-dimensional realignment of the images. The activity in the visual cortex was higher during visual stimulation than during the visual deprivation (P = 0.002, 17.6 +/- 8.6% increase) and baseline conditions (P = 0.009, 8.8 +/- 5.6% increase). Furthermore, the activity in the visual cortex was lower during the visual deprivation than in the baseline condition (P = 0.001, 8.1 +/- 2.9% decrease). 99TCm-HMPAO SPET, even with a single-head system, is capable of detecting changes in rCBF in the striate cortex, not only between conditions of visual stimulation and deprivation, but also between these two conditions and the baseline state.

Evaluation of algorithms for the registration of 99Tcm-HMPAO brain SPET studies.

Five functions of merit were used for the registration of 99Tcm-HMPAO brain SPET studies. The correlation coefficient (COR), the stochastic sign change (SSC), the standard deviation of ratios (SDR), the sum of the absolute differences (SAD) and a new function based on a local correlation coefficient (LOC) were tested in the registration of photic neuroactivation (ACT), epilepsy (EPL) and Wada (WAD) SPET studies. The comparison included simulated and real studies. The translation error in registration was 0.1 +/- 0.1 pixels (mean +/- S.D.) for all functions of merit for the complete set of simulated studies (10 runs for each ACT, EPL and WAD). For rotation, LOC yielded the best results with a mean error of 0.3 +/- 0.2 degree and a maximum error of 0.6 degree. Slightly higher errors were found with SAD (0.4 +/- 0.2 degree, maximum 1.0 degree) and COR (0.5 +/- 1.0 degree, maximum 1.0 degree). The highest errors were found with SDR (0.8 +/- 1.0 degree, maximum 4.8 degrees) and SSC (0.8 +/- 1.1 degrees, maximum 4.7 degrees). The results obtained from five real studies of ACT, of EPL and of WAD were in agreement with the findings from the simulated studies, thus confirming the robustness of LOC, SAD and COR for the registration of 99Tcm-HMPAO brain SPET studies.

Radioimmunoscintigraphy of colorectal carcinoma with a 111In-labelled anti-TAG-72 monoclonal antibody.

Radioimmunoscintigraphy (RIS) of colorectal carcinoma with a 111In-labelled anti-TAG-72 monoclonal antibody (CYT-103) has been performed in 24 patients with five primary lesions and 10 suspicious of recurrence (in one of these patients two RIS were made). Histopathological confirmation of the disease and surgical liver examination were carried out in all primary tumours and in 12 possible recurrences. In the remaining eight patients a final diagnosis was established according to the clinical course and other diagnostic procedures. Planar and tomographic scans were obtained at 48 and 72 h postinjection in all patients. All primary tumours were detected by RIS. In the group with recurrences confirmed pathologically the results were nine true positive, two true negative and one false positive in a patient affected only with liver disease. The nine true positive studies corresponded to four positive by computed tomography (CT), four negative by CT and one nonconclusive by CT. Surgical liver examination results were 15 true negative and two false negative. No correlation was found between serum levels of carcinoembryonic antigen or TAG-72 and the detection of the lesions. In 10 patients human anti-mouse antibody (HAMA) levels were studied. In conclusion, RIS with an anti-TAG-72 monoclonal antibody is a useful technique for the study and localization of colorectal tumours, mainly in cases of recurrence, being also indicated in patients with normal TAG-72 serum levels.

99Tcm-HMPAO leucocyte scintigraphy in the diagnosis of bone infection.

The utility of 99Tcm-HMPAO leucocytes has been studied in combination with 99Tcm-MDP bone scanning in the diagnosis of bone infection in a series of 50 patients with a clinical suspicion of bone infection. Thirty-three patients were referred to our Service from the Department of Orthopaedic Surgery (Group A) and seventeen from the Infectious Disease Unit (Group B). A total of 52 lesion sites were studied. The leucocyte and bone studies were performed within four days. The leucocyte scan was obtained at 30-60 min and 4-6 h after i.v. injection of 370 +/- 74 MBq of 99Tcm-HMPAO leucocytes. After confirming the scintigraphic findings, the results obtained were: Group A, 12 true positive, 21 true negative and 2 false positive; and in Group B, 5 true positive, 9 true negative and 4 false negative. The overall sensitivity was 80.9% with a specificity of 93.7%. Although the high bone marrow activity seen with 99Tcm-HMPAO leucocytes may reduce sensitivity, very good results were obtained in bone infection. The use of 99Tcm means great progress in the radiolabelling of white blood cells in terms of availability and better image quality. The combination of 99Tcm-HMPAO leucocytes and 99Tcm-MDP can be recommended as one of the most suitable methods for use in the diagnosis of bone infection, especially in patients with previous bone disease.

Detection and quantitative analysis of joint activity inflammation with 99Tcm-polyclonal human immunoglobulin G.

99Tcm-polyclonal human immunoglobulin G (HIG) scintigraphy was used to detect active joint inflammation and to obtain ratios of joint uptake in noninvolved and inflammatory joints. Imaging was performed at 4 and 24 h in 16 patients with rheumatoid arthritis (RA) and 16 with degenerative joint disease (control group). All joints (total of 1344) were scored for pain, swelling and visual analysis of uptake in both scans. Joint to background (J:B) ratios were also calculated. Clinical and visual scores correlated in both scans (r = 0.7, P < 0.01). In RA patients, 246 joints were clinically involved. Visual analysis of scans detected 213 (87%) of them at 4 h and 196 (80%) at 24 h. Joints with no pain or swelling showed significantly higher J:B ratios than the control group and lower ratios than joints clinically involved. In the control group, statistically significant differences in J:B ratios between the various joints were found, so it was necessary to establish a normal range for every joint. J:B ratios were significantly higher at 4 h than at 24 h in both groups of patients. 99Tcm-HIG scintigraphy allows detection and measurement of joint inflammation. Scans performed at 4 h are preferable to scans at 24 h. Quantitative analysis can measure more objectively the degree of activity and could be useful in the management of these patients.

67Ga scintigraphy for the evaluation of recurrences and residual masses in patients with lymphoma.

67Ga scintigraphy has proven to be of value in the evaluation of patients with lymphoma, especially in their management after treatment. In this study, computed tomography (CT) and 67Ga scans were compared in 53 patients with lymphoma who had previously been treated. Twenty-eight were patients in continuous clinical remission in whom recurrence was suspected. The remaining 25 patients were studied between 1 and 3 months post-treatment to assess a residual mass. The sensitivity for the detection of lymphoma recurrence was 88% for 67Ga, with two false-negative results, and 59% for CT, with seven false-negative results. In the diagnosis of recurrence, the specificity of 67Ga was 100% and that of CT 72%, with three false-positive results. Therapeutic response was assessed in 25 patients and the ability to predict response to treatment resulted in a specificity of 86% for 67Ga and 81% for CT. Treatment failed in four patients, as detected by 67Ga scan, whereas CT did not detect any of these. In the remaining 21 patients who showed good response to treatment, there were three false-positive results for 67Ga and four for CT. 67Ga scintigraphy can detect relapse more accurately and much earlier than CT, as well as diagnose complete remission after treatment. Therefore, 67Ga scintigraphy should be used routinely in monitoring response to treatment in lymphoma.

Scintigraphic evaluation of the severity of inflammation of the joints with 99TCm-HIG in rheumatoid arthritis.

A prospective study was carried out to determine the usefulness of 99TCm-human immunoglobulin G (HIG) scintigraphy in the assessment of the severity of joint inflammation. Twenty-four patients with rheumatoid arthritis were studied. The presence or absence of pain and/or swelling was evaluated in 34 joints and a clinical index taking into account the surface area of each joint was calculated. We measured the following biological markers of inflammation activity: erythrocyte sedimentation rate, C-reactive protein, haemoglobin, platelet count, serum levels of IL-6, TNF-alpha and soluble receptors of IL-2. Scintigraphic was performed 4 h after the injection of 740 MBq 99Tcm-HIG. The scans were evaluated by visual and quantitative analysis and the scores in each joint were weighted for joint size. Pathological uptake of the radiopharmaceutical was noted in 46% (24/52) of joints evaluated as painful, 89% (146/164) of swollen joints and 94% (78/83) of both painful and swollen joints. Both the visual and the quantitative scintigraphic indices correlated significantly with the clinical index, the number of painful joints, the number of swollen joints and several biological markers of inflammation. A very high correlation was also found between the visual and the quantitative scintigraphic indices (r = 0.91, P < 0.0001). In conclusion, 99Tcm-HIG scintigraphy is an objective test to detect synovitis and to assess the severity of inflammation. A careful visual analysis of scans is good enough for routine evaluations and computer quantitative analysis should be used when more accurate intra-individual variation is required.

Radioimmunoguided surgery of colorectal carcinoma with an 111In-labelled anti-TAG72 monoclonal antibody.

Radioimmunoscintigraphy (RIS) and radioimmunoguided surgery (RIGS) were assessed for their usefulness in patients with colorectal carcinoma. Twenty-nine patients (18 primary tumours, 10 with a suspicion of recurrence and one colonic diverticulitis) were studied. Radioimmunoscintigraphy was performed 48 and 72 h after the injection of an anti-TAG72 monoclonal antibody (CYT-103) labelled with 111In. Radioimmunoguided surgery was performed between 72 and 96 h post-injection. During surgery, a systematic screening was performed with a hand-held gamma detecting probe and a surgical index (tumour-to-normal tissue) was obtained. There were statistically significant differences between counts in normal tissue versus tumour (P < 0.001) and RIGS was considered positive for the detection of tumour if the ratio between the counts in the area suspicious of tumour and the counts in the normal tissue was greater than 1.5. The overall sensitivity for RIS and RIGS was 71.4% (55.6% in primary tumours and 100% in recurrences) and 82.1% (83.3% in primary tumours and 80% in recurrences), respectively. Radioimmunoguided surgery changed the surgical procedure in two cases with small tumour deposits. Occult regional lymph node involvement in primary tumours was not found; therefore, RIGS, as a complementary technique to RIS, is particularly useful in recurrences and can help the surgeon in the resection of small tumour deposits which are difficult to localize.