Clinical validation of the avidin/indium-111 biotin approach for imaging infection/inflammation in orthopaedic patients.

We report here the results of a validation study of the avidin/indium-111 biotin approach in patients with skeletal lesions. This study involved 54 patients with orthopaedic conditions: 20 patients with intermediate suspected osteomyelitis of the trunk, 19 patients with infection/inflammation of prosthetic joint replacements, and 15 patients with suspected osteomyelitis of appendicular bones. Avidin (3 mg) was injected as an i.v. bolus, followed 4 h later by 111In-biotin; imaging was acquired 30 min and 16-18 h after administration of 111In-biotin. Technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO)-labelled leucocyte scintigraphy was performed in 39/54 patients. The overall sensitivity of the avidin/111In-biotin scan was 97.7% (versus 88.9% for 99mTc-HMPAO leucocyte scintigraphy). While the diagnostic performance of avidin/111In-biotin scintigraphy was similar to that of 99mTc-HMPAO leucocyte scintigraphy in patients with prosthetic joint replacements or osteomyelitis of appendicular bones, the avidin/111In-biotin approach clearly performed better than 99mTc-HMPAO leucocyte scintigraphy in patients with suspected osteomyelitis of the trunk (100% sensitivity, specificity and accuracy versus 50% sensitivity, 100% specificity and 66.7% accuracy for 99mTc-HMPAO-leucocyte scintigraphy). These results demonstrate the feasibility of the avidin/111In-biotin approach for imaging sites of infection/inflammation in the clinical setting. Although no systematic advantages of avidin/111In-biotin scintigraphy were found versus 99mTc-HMPAO leucocyte scintigraphy, the newer scintigraphic method is more practicable and involves lower biological risk for the operators.

Trocar site tumor recurrences. May pneumoperitoneum be responsible?

BACKGROUND: Port site metastasis following laparoscopy for cancer is reported with increasing frequency and represents one of the most important limitations of the technique. METHODS: A scintigraphic model was utilized to evaluate a possible role of pneumoperitoneum in tumor cell dissemination. Labeled red blood cells (RBC) were injected at the level of the gallbladder bed during laparoscopic cholecystectomy (LC) performed for symptomatic cholecystolithiasis. LC was performed in two groups with standard CO2 pneumoperitoneum: in one group an endobag for retrieval of the specimen was utilized. In one group a gasless LC with endobag was performed. RESULTS: Radioactivity in the area of the trocar introduction was observed in almost all the patients who underwent standard (CO2) LC but represented a rare event in patients treated with the gasless method. The utilization of a protective bag for the extraction of the surgical specimen did not modify significantly the results. Moreover all patients treated with pneumoperitoneum demonstrated a wide intraperitoneal diffusion of the tracer not observed in gasless patients. CONCLUSIONS: The results of this study confirm that pneumoperitoneum may play an important role in the evolution of port site metastasis after laparoscopy for gastrointestinal cancer.

Multicenter randomized controlled clinical trial to evaluate cardioprotection of dexrazoxane versus no cardioprotection in women receiving epirubicin chemotherapy for advanced breast cancer.

PURPOSE: Dexrazoxane was found effective in reducing doxorubicin cardiotoxicity when given at a dose ratio (dexrazoxane: doxorubicin) of 20:1. Preclinical studies indicated that dexrazoxane at a dose ratio of 10 to 15:1 also protected against epirubicin-induced cardiotoxicity. The main objective of this study was to investigate the efficacy of dexrazoxane, given at a dose ratio of 10:1 against epirubicin cardiotoxicity. PATIENTS AND METHODS: One hundred sixty-two advanced breast cancer patients were randomized to receive epirubicin-based chemotherapy with or without dexrazoxane. Patients who had previously received adjuvant chemotherapy that contained anthracyclines were treated with cyclophosphamide 600 mg/m2 intravenously (IV), epirubicin 60 mg/m2 IV, and fluorouracil 600 mg/m2 IV, on day 1 every 3 weeks. The other patients were treated with epirubicin 120 mg/m2 IV on day 1 every 3 weeks. Cardiac toxicity was defined as clinical signs of congestive heart failure, a decrease in resting left ventricular ejection fraction (LVEF) to < or = 45%, or a decrease from baseline resting LVEF of > or = 20 EF units. RESULTS: One hundred sixty patients were evaluated. Cardiotoxicity was recorded in 18 of 78 patients (23.1%) in the control arm and in six of 82 (7.3%) in the dexrazoxone arm. The cumulative probability of developing cardiotoxicity was significantly lower in dexrazoxane-treated patients than in control patients (P = .006; odds ratio, 0.29; 95% confidence limit [CL], 0.09 to 0.78). Noncardiac toxicity, objective response, progression-free survival, and overall survival were similar in both arms. CONCLUSION: Dexrazoxane given at a dexrazoxane:epirubicin dose ratio of 10:1 protects against epirubicin-induced cardiotoxicity and does not affect the clinical activity and the noncardiac toxicity of epirubicin. The clinical use of dexrazoxane should be recommended in patients whose risk of developing cardiotoxicity could hamper the eventual use and possible benefit of epirubicin.

Simultaneous dobutamine stress echocardiography and dobutamine scintigraphy (99mTc-MIBI-SPET) for assessment of coronary artery disease.

BACKGROUND: Simultaneous dobutamine stress echocardiography (DSE) and 99Tc-MIBI-SPET (DMS) for the evaluation of the presence and the extent of coronary artery disease (CAD) were assessed for a head to head comparison regarding the diagnostic acuracy of the two rests. METHODS AND RESULTS: Forty-five consecutive patients (33 males and 12 females: 53 +/- 6.8 yr.) underwent exercise electrocardiography and simultaneous dobutamine stress echocardiography and MIBI-SPET imaging. Coronary angiography was performed in all patients (significant coronary stenosis > 50%). On the basis of the results of exercise electrocardiogram the pre-test probability for coronary artery disease (Diamond's algorithm) was low (45.6 +/- 12.7%). The overall specificity, sensitivity and predictive accuracy of Echo-dobutamine stress test for diagnosis of the presence or absence of CAD were: specificity 82%, sensitivity 76%, diagnostic accuracy 80%, positive predictive value 90%, negative predictive value 40%. The overall specificity, sensitivity and predictive accuracy of MIBI-SPET-dobutamine test for diagnosis of the presence or absence of CAD were: specificity 86%, sensitivity 87%, diagnostic accuracy 84%, positive predictive value 97%, negative predictive value 54%. MIBI-SPET-dobutamine test showed a significantly higher sensitivity in comparison with ECHO-dobutamine test (P < 0.05). CONCLUSION: Both noninvasive methods for the detection of CAD showed a good diagnostic accuracy. Nevertheless the SPET model showed a higher sensitivity in comparison with DSE model, essentially in the presence of a lower extent of CAD and during submaximal test.

Comparison among sonography, double-tracer subtraction scintigraphy, and double-phase scintigraphy in the detection of parathyroid lesions.

OBJECTIVE: This study prospectively evaluated the sensitivity of high-resolution sonography compared with double-tracer 201Tl-99mTc scintigraphy (Tl-Tc) subtractive scintigraphy and double-phase 99mTc-sestamibi (Tc-MIBI) scintigraphy prior to surgery in the assessment of patients with primary hyperparathyroidism in a geographic region where areas of endemic thyroid goiter are present. SUBJECTS AND METHODS: Sonography and scintigraphy were used as first-step imaging procedures in 73 patients with primary hyperparathyroidism. In 30 (41%) of 73 cases, we found an association with a thyroid abnormality. We compared sonography with double-tracer Tl-Tc scintigraphy in 41 cases, with Tc-MIBI scintigraphy in 22 other cases, and with both scintigraphic studies in 10 other cases. RESULTS: Surgery demonstrated 68 solitary parathyroid lesions (66 adenomas, one hyperplasia, and one carcinoma), two adenomas in two patients, and multiple hyperplastic glands in two patients for a total of seven lesions. In one case no abnormal parathyroid gland was found. Overall sensitivity of sonography, Tl-Tc, and Tc-MIBI scintigraphy was 85%, 62%, and 82%, respectively. In patients with concomitant thyroid disease, the sensitivity of sonography, dual-tracer Tl-Tc, and Tc-MIBI was 77%, 67%, and 80%, respectively. CONCLUSION: Our study proves that sonography and scintigraphy are equally able to detect parathyroid lesions before surgery in patients with concomitant thyroid diseases. In patients without thyroid abnormalities, detection rates of sonography and Tc-MIBI do not show any statistical difference, and the detection rate of Tl-Tc is significantly inferior to that of sonography. Sonography alone should be used as the first step for localization of abnormal parathyroid glands prior to surgery, and Tc-MIBI scintigraphy should be used as the second step when sonography is negative.

Incremental diagnostic value of dobutamine stress echocardiography and dobutamine scintigraphy (technetium 99m-labeled sestamibi single-photon emission computed tomography) for assessment of presence and extent of coronary artery disease.

BACKGROUND: The incremental diagnostic value of dobutamine stress echocardiography (DSE) and 99mTc-labeled sestamibi single-photon emission computed tomography for the evaluation of the presence and extent of coronary artery disease (CAD) was assessed with ordered logistic regression and receiver-operating characteristic curves. METHODS AND RESULTS: Forty-five consecutive patients (33 men and 12 women; 53 +/- 6.8 years) underwent exercise electrocardiography and simultaneous DSE and sestamibi single-photon emission computed tomographic imaging. Coronary angiography was performed in all patients (significant coronary stenosis > 50%). On the basis of the results of exercise electrocardiography, the pretest probability for CAD (Diamond's algorithm) was low (45.6% +/- 12.7%). According to ordered logistic regression analysis, some models were estimated that performed a diagnostic accuracy level for CAD. In particular, we evaluated a clinical model (model 1) determined by the following parameters: sex, age, presence of chest pain, and positivity of electrocardiogram during dobutamine stress test. This model was 64.3% +/- 10.7% accurate for the prediction of CAD. The addition to model 1 of DSE parameters (wall motion stress and rest score index and relative difference) (model 2) yielded a diagnostic accuracy of 81.4% +/- 4.3% (p < 0.045), whereas the addition to model 1 of single-photon emission computed tomographic parameters (the difference between perfusional stress and rest score index) (model 3) improved diagnostic accuracy to 92.3% +/- 5.5% (p < 0.003), a level that appeared significantly higher than that of model 2 (p < 0.016). CONCLUSION: Both noninvasive methods for the detection of CAD showed a good diagnostic accuracy, especially when test-derived parameters were combined with clinical data. Nevertheless, the single-photon emission computed tomographic model showed a higher sensitivity compared with the DSE model.

[The imaging diagnosis of Sjögren's syndrome: echography, sialography and scintigraphy compared in the study of the salivary glands]. / Diagnostica per immagini della sindrome di Sjögren: ecografia, scialografia e scintigrafia a confronto nello studio delle ghiandole salivari.

The aim of the present study was to evaluate the sensitivity and specificity of the ultrasonography, in comparison with other methods of investigation (scintigraphy, sialography, and biopsy), in scanning morphostructural changes in the parotid gland in patient with Sjögren's syndrome. During the period June-October 1994, 34 patients (5 males and 29 females, age ranged between 20 and 88 years) with "sicca syndrome" underwent to echography, scintigraphy, sialography and biopsy. The diagnosis was confirmed or excluded using the European Community Epidemiologic Committee criteria for Sjögren's syndrome. Twenty-two patients out of 34 were affected by Sjögren's syndrome, while the others resulted as control subjects. The ultrasonographic investigation has shown 76.19% of sensitivity and 30.43% of specificity. Even if echography is a non-invasive method, which could be used as preliminary approach for studying the diffused involvement of the parotid gland, at the status of the art, it is not completely reliable for the global evaluation of the morphostructural changes in patients with Sjögren's syndrome, in comparison with the other techniques. Because of the double nature of the gland injury, it appears to be essential the diagnostic integration between echography and sialography.

Scintigraphic findings on 99mTc-MDP, 99mTc-sestamibi and 99mTc-HMPAO images in Gaucher's disease.

Gaucher s disease is an autosomal recessive lysosomal storage disease characterized by the specific deficiency of glucocerebrosidase that leads to accumulation of insoluble glucocerebroside in the reticuloendothelial system, particularly the bone marrow, liver, spleen and lymph nodes. Direct scintigraphic visualization of lipid deposits in Gaucher s disease has recently been described, based on the use of the lipid-soluble xenon-133. We report here on the use of the lipophilic cationic complex technetium-99m sestamibi (99mTc-MIBI), employed as an indicator of increased cellular density and metabolic activity, to evaluate Gaucher cell infiltrates in the bone marrow; 99mTc-hexametazime (99mTc-HMPAO) was also employed, as a pure indicator of lipidic infiltration in the bone marrow. A 67-year-old patient with known type 1 Gaucher s disease presented with a painful left hip and knee and difficulty in gait subsequent to traumatic fracture of the left femoral neck that had required implant of a fixation screw-plaque. Bone scan with 99mTc-methylene diphosphonate revealed reduced uptake at the distal metaphyseal-epiphyseal femoral region. In addition, whole-body maps and spot-view acquisitions of the thighs and legs were recorded at both 30 min and 2.5 h after the injection of 99mTc-MIBI: the scintigraphic pattern clearly showed increased uptake at several sites involved by Gaucher deposits in the bone marrow (both knees, with variable intensity in different areas), matching the bone changes detected by conventional x-ray. The target to non-target ratios slowly decreased with time, from an average value of 2.25 in the early scan to an average value of 2 in the delayed scan. The lipid-soluble agent 99mTc-HMPAO exhibited a superimposable scintigraphic pattern of accumulation at the involved sites, though with lower target to non-target ratios (1.27-1.48). The results obtained in this patient suggest a potential role of 99mTc-MIBI in the scintigraphic evaluation of Gaucher s lipid deposits in the bone marrow. If the results are confirmed in other patients, this radiopharmaceutical would offer clear advantages over 133Xe because of its wider availability and greater practicality (i.v. administration of 99mTc-MIBI versus inhalation of 133Xe, and use of a single gamma camera instead of two as with 133Xe).

Bone involvement in Gaucher's disease: 'bone crisis' or disease complication?

Bone involvement can represent the inaugural symptom of Gaucher's disease (GD). Here, we report the case of a 68-year old man diagnosed as having GD since 1963. In June 1994 the patient was referred to our Rheumatology Unit because of a long-lasting coxalgia on the left hip and progressive walking impairment following traumatic fracture of the left femur. Multicystic osseous changes at standard X-ray and hyper-gamma-globulinemia with an elevated ESR (122 mm, 1st hour) suggested the diagnosis of either osteonecrosis of the femoral head or multiple myeloma. On bone marrow biopsy examination, Gaucher's cell infiltrates were detected and an increased uptake in the distal left femur and proximal tibia were demonstrated by lipophilic tracer scan (99mTc-Sestamibi). Subsequently, the patient suffered another femoral fracture at a site of Gaucher's infiltrates previously documented by bone scan. We conclude that in patients with GD, 99mTc-Sestamibi bone scan can selectively evaluate the presence of bone lipid deposits, and could indirectly differentiate this bone condition from other serious skeletal complications of the disease.

[Preoperative imaging in the detection of parathyroid tumefaction in patients with primary hyperparathyroidism. The authors' own experience]. / Imaging preoperatorio nella ricerca di una tumefazione paratiroidea nei pazienti con iperparatiroidismo primitivo. Esperienza personale.

The authors report their 3-year experience with the diagnosis of parathyroid lesions in primary hyperparathyroidism patients in a geographic area where the occurrence of endemic goiter is medium. Our study was aimed at prospectively assessing preoperative imaging results in these patients. The following imaging methods were used: high-definition and color-Doppler ultrasonography (US), double-tracer 201Thallium-99mTechnetium (T1/Tc) subtraction scintigraphy, Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and US-guided fine-needle aspiration of the suspected parathyroid lesions. Preoperative US and scintigraphy were performed in 50 patients with primary hyperparathyroidism; in addition, color-Doppler US studies were performed in 33 patients for vascular characterization of the lesions. In 19 patients, the suspected lesions were punctured under US guidance to measure parathormone (PTHa) and thyroglobulin (TGa) levels in the aspirated material. CT and MRI were performed in 9 patients, to identify a possible ectopic parathyroid gland. Surgery demonstrated 48 solitary parathyroid lesions and one double parathyroid adenoma. In one patient no abnormal parathyroid gland was found. Overall sensitivity rates of US and scintigraphy were 85.7% and 61.2%, respectively. In multinodular goiter patients, the sensitivity rates of US and scintigraphy were 71.4% and 47.6%, respectively. At color-Doppler US the presence of parenchymal vascularization was specific of parathyroid nodules and the method helped differentiate parathyroid lesions from thyroid nodules in 14 multinodular goiter patients. Overall PTHa sensitivity was 72.2% and its specificity 100%. Overall TGa sensitivity was 100% and specificity 94.7%. CT and MRI allowed the detection of 8 ectopic parathyroid lesions. In conclusion, in our personal experience, US should be preferred to double-tracer T1/Tc subtraction scintigraphy in the early examination of primary hyperparathyroidism patients. When US detects a suspected parathyroid lesion, color-Doppler US and PTH and TG sampling can make useful diagnostic tools for reducing false-positive results, especially when thyroid disease is associated.

Initial tumor targeting, biodistribution, and pharmacokinetic evaluation of the monoclonal antibody PAM4 in patients with pancreatic cancer.

This pharmacokinetic study was performed to assess the potential usefulness of the murine monoclonal antibody (MoAb) PAM4-IgG1 as an immunotargeting agent for pancreatic cancer imaging or therapy. This MoAb reacts specifically with mucin purified from human pancreatic cancer. 131I-labeled PAM4-IgG1 was injected i.v. into five patients with suspected pancreatic cancer. Whole-body scans and spot views of the abdominal area were recorded with a computerized gamma camera, and specific regions of interest were drawn over the liver and spleen to define the kinetics of activity in these organs. Blood samples taken from 0.1-144 h after injection served to define the kinetics of plasma distribution and removal of activity from the body. Surgery confirmed pancreatic cancer in four of the five patients, whereas chronic pancreatitis was present in the fifth patient; in all four pancreatic cancer patients, immunostaining with the MoAb PAM4 demonstrated the presence of the specific antigen, with a cytoplasmic and endoluminal/secretory pattern of distribution. Nonspecific radioactivity accumulation in the liver, spleen, and bone marrow was low, linked essentially to the blood pool effect of circulating activity in these organs. The overall quality of scintigraphic maps recorded over the abdomen was quite satisfactory due to the low liver and spleen activity, with good scintigraphic demonstration of the pancreatic cancers (either primary or metastatic); the patient subsequently found to have pancreatitis failed to show PAM4 targeting. Except in one patient with widespread peritoneal metastases (in whom these tumor implants were detected scintigraphically already 24-48 hours after tracer injection), scintigraphic evidence of the tumor lesions was usually late, starting at about 72-96 h after tracer injection. The results obtained in this preliminary study indicate the potential usefulness of MoAb PAM4 for immunoscintigraphy in patients with either primary and/or recurrent pancreatic cancer while also suggesting that the use of the faster-clearing Fab fragments of this MoAb probably would result in improved immunoscintigraphic properties.

Localization of [125I]endothelin-1 in injured aorta of rabbits.

Endothelin-1 is a potent vasoconstrictor. This study was performed to determine whether arterial injury, induced by either hypercholesterolemia or mechanical disruption of the endothelium, is associated with increased localization of endothelin-1 in the artery. The blood clearance and tissue distribution of intravenously injected [125I]endothelin-1 was evaluated in 33 rabbits--control animals (n = 7), balloon de-endothelialized animals (n = 12), cholesterol-fed animals (n = 6) and animals that had both balloon de-endothelialization and high cholesterol diet (n = 8). The blood clearance half time was less than 10 min, with slightly slower clearance in the ballooned/cholesterol-fed animals. [125I]Endothelin-1 localized in the lung (approximately 12% injected dose (ID)/organ) and kidney (approximately 8%ID/organ). [125I]Endothelin-1 localization in the injured aorta increased from the baseline level of 0.06%kgID/g to its highest level within 5 min of balloon de-endothelialization (0.2%kgID/g) and decreased to 0.11%kgID/g within one week and remained essentially unchanged through 16 weeks. The area with increased binding of [125I]endothelin-1 corresponded to the zone of arterial injury stained with Evans blue. On the other hand, the binding in the aorta did not increase with the atherogenic diet. These findings suggest that endothelin-1 accumulates in injured vessels, attaining the highest levels immediately after mechanical injury.

Incremental diagnostic value of dipyridamole echocardiography and exercise thallium 201 scintigraphy in the assessment of presence and extent of coronary artery disease.

BACKGROUND: The incremental diagnostic information of two noninvasive tests for the detection of coronary artery disease (CAD), dipyridamole echocardiography, and exercise 201Tl myocardial scintigraphy was assessed in a series of 102 patients with ordered logistic regression and receiver-operating characteristic curves. METHODS AND RESULTS: Patients were selected from those referred to our cardiovascular centers with the clinical suspicion of CAD. After clinical evaluation, all patients underwent both noninvasive tests during hospitalization 2 weeks before coronary arteriography. The coronary arteriogram was used as a gold standard: CAD was defined as the presence of one or more vessels with 50% or greater narrowing of the luminal diameter. Clinical data were 73.0% +/- 5.7% accurate in the prediction of CAD. The addition of dipyridamole echocardiographic data to the clinical model yielded a diagnostic accuracy of 88.3% +/- 4.3% (p < 0.00001), whereas the addition of thallium scintigraphic parameters to the clinical model improved diagnostic accuracy to 93.8% +/- 2.6% (p < 0.00001). A significant increase in accuracy to 97.2% +/- 1.4% was achieved when thallium scintigraphic data were added to the clinical and dipyridamole-echocardiographic model (p < 0.00001). CONCLUSION: Both noninvasive methods for detection of CAD, DET, and ETS showed a good diagnostic accuracy especially when tests-derived parameters were combined with clinical data by means of relative logistic models; nevertheless the ETS model showed a higher sensitivity in comparison with the DET model, essentially in presence of a lower extent of CAD.

Chromatographic identification in serum of endogenously radioiodinated thyroid hormones after iodine-131 whole-body scintigraphy in the follow-up of patients with differentiated thyroid carcinoma.

Patients with differentiated thyroid cancer (DTC) are conventionally followed with serial 131I whole-body scintigraphy (WBS) and serum thyroglobulin (hTg) assay. Given the 15%-20% incidence of discordant results, we developed a sensitive and specific procedure for monitoring such patients, based on the assumption that 131I uptake, even if too low to be detected by 131I WBS, could be assayed in serum as thyroid products (hTg, T3 and T4) endogenously labeled with 131I. Our study included 125 patients routinely monitored for tumor recurrence or for the persistence of functioning thyroid tissue after complete primary treatment for DTC (surgery and 131I ablation of remnants). A plasma sample, taken 72 hr after administering 131I for WBS was fractionated on a Sephadex-G25 superfine column by first eluting all of the radioactive species except the thyroid hormones and then the radioiodothyronines. The sensitivity and specificity of chromatography in detecting functioning thyroid tissue after primary treatment for DTC were 98.4% and 100% (accuracy 99.2%), respectively, versus 90.6% and 95.1% for 131I WBS (accuracy 92.8%) and 60.9% and 100% for hTg (accuracy 80%). Combining chromatography with serum hTg gave the highest gains in diagnostic performance (100% for all parameters). This chromatographic method can be used in addition to conventional procedures in the follow-up of patients with DTC and represents a highly sensitive test for assessing the results of 131I ablation of postsurgical remnants.

Scintigraphic evaluation of biliary leakage following laparoscopic cholecystectomy.

Three patients with biliary leakage following coelioscopic cholecystectomy after percutaneous drainage of abdominal collection underwent 99m Tc TRIMETHYL-BROMO IDA biliary scintigraphy. In all cases, scintigraphy showed the site of the leak with a good dynamic evaluation of tracer confirming the adequacy of percutaneous drainage. Two patients were treated conservatively; one underwent surgical repair of a common bile duct lesion because of the high output of bile despite nasobiliary drainage. Biliary scintigraphy provides useful information in case of suspicious biliary leakage after coelioscopic cholecystectomy.

[Use of SPECT in the diagnosis of vertigo syndromes of vascular nature]. / Impiego della S.P.E.T. nella diagnosi delle sindromi vertiginose di natura vascolare.

Dizziness is doubtlessly one of the most common symptoms to arise in ischemia of the brainstem. In such cases the circulatory deficit can not only cause a direct lesion of the vestibular structures but it may also block the compensatory process. There are, however, significant difficulties in establishing whether such dizziness can be attributed to a brainstem insufficiency (BI). In fact, both CAT and NMR provide data only in the case of permanent CNS tissue lesions and tests such as the Doppler examination of neck blood vessels are unable to establish the true state of cerebral blood flow. In order to obtain semi-quantitative data regarding cerebral blood flow 99mTc-HMPAO-S.P.E.T. (Single Photon Emission Tomography) was used in 18 patients suffering from dizziness and for whom there was strong indication that the underlying cause could be vascular. There was a discrepancy between the Doppler and S.P.E.T. findings in 50% of the cases. CAT, however, proved negative in all but one of the cases. These data indicate that Doppler testing of the neck blood vessels can provide useful information regarding the status of the cerebral-afferent vessels but that these cannot be correlated to the level of cerebral blood flow. On the other hand, with S.P.E.T., in 15 of the 18 patients, it proved possible to identify significant alterations in cerebral blood flow in the absence of any permanent tissue lesions as those revealed by CAT and NMR. In the light of the present results cerebral S.P.E.T. appears to be a highly valid tool when, faced with dizziness for which a vascular origin is suspected, one must evaluate cerebral prognosis and therapy.

High-performance liquid chromatographic separation of iodoamino acids for tracer turnover studies of thyroid hormones in vivo.

A reversed-phase high-performance liquid chromatographic technique was developed to separate radioiodinated thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3) and two diiodothyronines (3,3'-T2 and 3',5'-T2), in extracts from either serum or urine. Chromatography was performed with 10-micron C18 silica gel, packed in a glass column (3 X 300 mm); the mobile phase was methanol-water (55:45) adjusted to pH 3 with H3PO4, at a flow-rate of 1.2 ml/min and a pressure of 2800 p.s.i. The results demonstrate the ability of the system to yield a clear-cut separation of the iodothyronines involved in in vivo turnover studies, i.e., T4, T3, rT3, and the two T2 compounds together.

Comparison of plasma and urinary methods for the direct measurement of the thyroxine to 3,5,3' - triiodothyronine conversion rate in man.

A further development of a new method recently proposed for the direct measurement of the conversion ratio (CR) of T4 to T3 in man is presented. [125I]T4 and [131I]T3 are injected simultaneously, and Sephadex chromatography is performed on urine samples to determine [125I]T3 formed in vivo, while plasma samples are used to measure the injected tracers. CR is calculated with the assumption that urinary [125I]T3 closely reflects [125I]T3 appearing in plasma after the injection of precursor [125I]T4. Four normal subjects and six patients with various thyroid disorders were studied using this method. The experimental data were also analyzed by our previous method based on plasma sampling only and by two recently described methods based on urinary measurements. These comparisons were made in an attempt to ascertain whether there is any systematic difference between the conversion values derived from plasma data and those derived from urinary data. Using plasma data alone, the CR was 28.6 +/- 3.4% (mean +/- SEM) in a group of four normal subjects, 37%, in two untreated hypothyroid patients, 40.2% in one hypothyroid subject receiving T4 treatment, 30.9% in one hyperthyroid patient, 24.9% in one patient with selective hyperthyroxinemia due to amiodarone treatment, and 10.7% in one normal subject after iopanoic acid administration. These values were in excellent agreement with those obtained by the modified procedure described here, in which both urinary and plasma measurements are used. Of the methods using urinary data alone, however, one gave similar results, while the other systematically overestimated the CR, possibly due to delayed excretion of labeled T4 metabolites into the urine. We conclude that 1) the analytical procedure to separate the labeled tracers and metabolites in urine or plasma is critical for the accurate estimation of CR; 2) when an adequate separation procedure is available, plasma and urinary methods for measuring CR yield comparable results; and 3) the plasma method should be used when, in addition to CR, other kinetic (distribution and turnover) parameters of T4 and T3 metabolism are to be estimated.