Lluis Berná

High prevalence of myocardial monoclonal antimyosin antibody uptake in patients with chronic idiopathic dilated cardiomyopathy

Monoclonal antimyosin antibody studies were undertaken to assess the presence of myocardial uptake in patients with chronic idiopathic dilated cardiomyopathy. Three groups were studied: 17 patients with chronic (greater than 12 months) idiopathic dilated cardiomyopathy, 12 patients with a large, poorly contracting left ventricle not due to dilated cardiomyopathy (control patients) and 8 normal individuals. The patients in the cardiomyopathy and control groups showed a similar degree of clinical and functional impairment. Imaging was undertaken 48 h after antimyosin injection. The heart/lung ratio of antimyosin uptake was used to assess the results. The mean ratio in the cardiomyopathy group was 1.83 +/- 0.36 (range 1.40 to 2.80), a value significantly higher than that obtained in the control patients without cardiomyopathy (mean 1.46 +/- 0.04, range 1.38 to 1.50) or normal subjects (mean 1.46 +/- 0.13, range 1.31 to 1.6) (p less than 0.01). No difference in the ratio was noted between the normal subjects and control patients. Abnormal antimyosin uptake was seen in 12 (70%) of the 17 patients with cardiomyopathy and in only 1 (8%) of the 12 control patients. Positive monoclonal antimyosin antibody studies are highly prevalent in chronic idiopathic dilated cardiomyopathy.

Noninvasive localization of human atherosclerotic lesions with indium 111-labeled monoclonal Z2D3 antibody specific for proliferating smooth muscle cells.

BackgroundTargeting exclusive antigens in atherosclerotic plaques with antibodies may provide a noninvasive means to detect rapidly proliferative atherosclerotic lesions. 111In-labeled negative charge-modified Z2D3 F(ab′)2 (Z2D3) specific for an antigen expressed exclusively by proliferating smooth muscle cells has been shown to accumulate in rabbit atherosclerotic plaques.MethodsThe safety, biodistribution, accumulation, and elimination of Z2D3 were assessed in 11 patients who were candidates for carotid endarterectomy. The presence of atheromas in these patients was confirmed by angiography and Doppler ultrasound. Z2D3 (250 μg) labeled with 5 mCi of 111In was administered by slow intravenous injection. Planar and single photon emission computed tomography (SPECT) images were obtained 4, 24, 48, and 72 hours later. Carotid endarterectomy was performed and the surgical specimens were imaged, weighed, gamma-counted, and analyzed by immunostaining.ResultsUptake of Z2D3 at the site of the carotid plaques was observed in the planar and SPECT views at 4 hours in all subjects. In addition, antibody uptake was noted in the contralateral vessel in 5 subjects. SPECT images identified the atherosclerotic plaques with focal uptake. The antibody uptake corresponded with the angiographic location of the disease. Immunohistochemical studies of the endarterectomy specimens confirmed the localization of Z2D3 into the plaque areas containing smooth muscle cells. Adverse drug reactions were not observed.ConclusionThis study demonstrates the feasibility of targeting atherosclerotic lesions with negative charge-modified antibody. It also proposes the possibility of selective identification of various components of atherosclerotic plaque, which may contribute to determining strategies of intervention in future.

Myocardial iodine-labeled metaiodobenzylguanidine 123 uptake relates to age

Background123I-labeled metaiodobenzylguanidine (123I-MIBG) is used increasingly to assess cardiac adrenergic neuron function. Few studies have reported data on myocardial MIBG uptake in relation to age, with contradictory results. This study reports the results of myocardial MIBG studies in untreated patients with cancer to assess the influence of age on myocardial MIBG uptake.Methods and ResultsThirty-nine patients with cancer enrolled in a study to assess the effect of doxorubicin administration on adrenergic neuron function underwent baseline studies with 123I-MIBG before chemotherapy. None of the patients had a history of neuropathy, previous cardiac disease, or previous chemotherapy or mediastinal radiotherapy. Myocardial MIBG uptake was quantified by a heart/mediastinal ratio (HMR) 4 hours after intravenous administration of 5 mCi, 123I-MIBG. The mean age of patients was 38 years, ranging from 16 to 75 years. Ten patients were below 20 years, 13 patients were between 20 and 40 years, six patients were between 40 and 60 years, and 10 patients were greater than 60 years of age. Myocardial 123I-MIBG uptake was observed in all patients, with a mean HMR of 1.85±0.29 (range 1.31 to 2.62). HMR correlated with age (r=−0.6264; p<0.001). A decrease in 123I-MIBG uptake with aging was observed. The mean HMR of patients of less than 20 years was 2.07, of patients between 20 and 40 years 1.89, of patients between 40 and 60 years 1.83, and of patients greater than 60 years 1.56. The best separation was observed comparing patients who were greater than 60 years (mean HMR 1.56 ± 0.16; range 1.31 to 1.78) with patients who were less than 60 years of age (mean HMR 1.95 ±0.;24; range 1.56 to 2.62; p=0.003).ConclusionsMyocardial 123I-MIBG uptake relates to age. A decrease in myocardial MIBG uptake is observed with aging, especially in those patients over 60 years of age. The influence of age on myocardial MIBG uptake has to be taken into account when studies are designed to assess cardiac adrenergic neuron function with 123I-MIBG.

Utility of 99mTc‐sestamibi scintigraphy as a first‐line imaging procedure in the preoperative evaluation of hyperparathyroidism

OBJECTIVE The use of preoperative imaging in patients with hyperparathyroidism remains controversial. Many of the available techniques are insufficiently sensitive and specific to justify their routine use. We have evaluated the Sensitivity and specificity of 99mTc‐sestamibi scintigraphy in the management of patients with different forms of hyperparathyroidism.

Assessment of anthracycline-induced myocardial damage by quantitative indium 111 myosin-specific monoclonal antibody studies

To assess chemotherapeutically induced myocardial damage, myosin-specific antibody scans and ejection fraction measurements were performed in 32 patients with breast cancer and in 9 patients with other tumours. All patients had received chemotherapy including anthracyclines. The ejection fraction decreased by ≥ 10% in 14 of 41 (34%) patients after chemotherapy. Antimyosin uptake in the myocardium was observed in 38 of 41 (92%) patients after chemotherapy. Antimyosin uptake was quantified by means of a heart-to-lung ratio, revealing a correlation between the degree of antimyosin uptake in the myocardium and the cumulative dose of anthracycline. Patients with a decreased ejection fraction showed more intense antimyosin uptake, indicating more severe myocardial damage. A higher degree of antimyosin uptake was found in 17 breast cancer patients treated with doxorubicin compared with 15 patients treated with mitoxantrone. We conclude that antimyosin studies provide a sensitive, non-invasive method to monitor myocardial damage in patients treated with anthracyclines. Antimyosin uptake in the myocardium precedes ejection fraction deterioration. This technique may be helpful in the early identification of patients at risk of congestive heart failure during chemotherapy including anthracyclines.

Efficacy of augmented immunosuppressive therapy for early vasculopathy in heart transplantation

OBJECTIVES The present study was undertaken to prospectively and comparatively evaluate the role of serial myocardial perfusion imaging and coronary angiography for the detection of early vasculopathy in a large patient population and also to determine the short- and long-term efficacy of augmented immunosuppressive therapy in the potential reversal of the early vasculopathy. BACKGROUND Allograft vasculopathy is the commonest cause of death after the first year of heart transplantation. Anecdotal studies have reported the efficacy of augmented immunosuppressive therapy after early detection of vascular involvement. However, no prospective study has evaluated the feasibility of early detection and treatment of allograft vasculopathy. METHODS In 76 cardiac allograft recipients, 230 coronary angiographic and 376 scintigraphic studies were performed in a follow-up period of 8 years. Angiography was performed at 1 month and every year after transplantation, and thallium-201 scintigraphy at 1, 3, 6 and 12 months after transplantation and twice a year thereafter. Prospective follow-up of 76 patients showed that 18 developed either angiographic or scintigraphic evidence of coronary vasculopathy. All episodes were treated with 3-day methylprednisolone pulse and antithymocyte globulin. RESULTS Twenty-two episodes of vasculopathy were diagnosed and treated in these 18 patients. Of these 22 episodes, two were detected only by angiography, seven by both angiography and scintigraphy, four by scintigraphy and histologic evidence of vasculitis and nine episodes only by thallium-201 scintigraphy studies. Angiographic and/or scintigraphic resolution was observed in 15 of the 22 episodes (68%) with augmented immunosuppression. The likelihood of regression was higher when treatment was instituted within the first year of transplantation (92%) than after the first year (40%) (p = 0.033). Eighty percent of patients who responded to follow-up. CONCLUSIONS The present study suggests that early detection of allograft coronary vasculopathy is feasible with surveillance myocardial perfusion or coronary angiographic studies. When identified early after transplantation, immunosuppressive treatment may result in regression of coronary disease.

Technetium-99m human polyclonal immunoglobulin G studies and conventional bone scans to detect active joint inflammation in chronic rheumatoid arthritis.

Rheumatoid arthritis is a chronic polyarthritis in which active inflammed joints coexist with joints in remission. We performed bone scans (99mTc-DPD) and 99mTc human polyclonal immunoglobulin G scans (99mTc-IgG) in 18 patients with rheumatoid arthritis to assess the uptake in actively inflamed joints and in joints in which remission after inflammation had occurred. A quantitative analysis of tracer uptake in each joint was performed on both scans. In 123 joints without current active inflammation, an increased 99mTc-DPD uptake was observed (2.31 ± 1.27), whereas no 99mTc-IgG uptake was noted (1.18±0.32). Some 78 joints with mild pain or swelling exhibited increased 99mTc-DPD uptake (2.48 ± 1.14) and increased 99mTc-IgG uptake (1.76 ± 0.50; P <0.001), while 21 joints with moderate to severe pain or swelling exhibited increased 99mTc-DPD uptake (2.39±0.93) and increased 99mTc-IgG uptake (1.79±0.51; P <0.001). In conclusion, 99mTc-IgG scans distinguish between joints with and without active inflammation in chronic rheumatoid arthritis, whereas bone scans do not. Thus, 99mTc-IgG scans may be useful in identifying joints with current active inflammation in rheumatoid arthritis.

Influence of the menstrual cycle and of menopause on the gastric emptying rate of solids in female volunteers

The aim of this study was to assess the influence of the normal menstrual cycle and of menopause on the gastric emptying rate of solids. Gastric emptying was studied in 15 premenopausal and ten postmenopausal women with an isotopic technique after the ingestion of a radiolabelled test meal. Premenopausal women were studied twice: within 1 week prior to menses and again 1 week after onset of menses. Postmenopausal women were studied only once. The emptying curves of the solid component of the meal fitted a linear model. The half-emptying time was 78±5 min during the follicular phase, 75 ± 7 min during the luteal phase and 76 ± 6 min in post-menopausal women (differences not statistically significant). The mean percentages of the meal retained in the stomach at different time intervals were also similar in the three groups. These results suggest that the menstrual cycle does not influence the gastric emptying rate of solids, which remains unchanged in relation to the follicular phase or after menopause.

Use of somatostatin analogue scintigraphy in the localization of recurrent medullary thyroid carcinoma

Abstract.Detection of recurrence of medullary thyroid carcinoma (MTC) remains a diagnostic problem. Increased serum tumour marker levels frequently indicate recurrence while conventional imaging techniques (CIT) are non-diagnostic. In this study, we performed indium-111 octreotide scintigraphy and CIT in a series of 20 patients with MTC presenting with elevated serum tumour markers after surgery. 111In-octreotide whole-body studies detected 15 pathological uptake foci in 11 of the 20 patients studied and CIT detected 17 lesions in 11 of the 20 patients. Ten patients underwent reoperation, five of them with positive 111In-octreotide scintigraphy and CIT and two with positive isotopic exploration and negative CIT. Surgical findings demonstrated that the results of isotopic study and CIT had been false-positive for MTC in one case (sarcoidosis). The six patients with true-positive 111In-octreotide studies had significantly higher basal calcitonin (CT) and carcinoembryonic antigen (CEA) levels than the patients with negative isotopic studies. The expression of somatostatin receptor (SSTR) subtypes by PC-PCR could be investigated in four cases with a positive isotopic study. Among the three cases with a true-positive study, SSTR2, the SSTR subtype that preferentially binds to the somatostatin analogue octreotide, was detected in two, SSTR5 was demonstrated in the three, and SSTR3 was detected in one. No subtype of SSTR was detected in the case with a final diagnosis of sarcoidosis. We conclude that 111In-octreotide has limited sensitivity in detecting recurrence in patients with MTC, although its sensitivity may improve with high serum CT levels. This radionuclide imaging technique should be employed when conventional imaging techniques are negative or inconclusive or when the presence of somatostatin receptors may provide the basis for treatment with somatostatin analogues.

Nitrate administration to enhance the detection of myocardial viability by technetium-99m tetrofosmin single-photon emission tomography

A comparison was performed between technetium-99m tetrofosmin myocardial perfusion tomography at baseline and after nitrate administration, using a 2-day protocol, and rest-reinjection thallium-201 single-photon emission tomography (SPET) studies in order to assess whether nitrates enhance the detection of viable myocardium with99mTc-tetrofosmin. Fifteen patients with coronary artery disease, previous myocardial infarction and a left ventricular ejection fraction <40% underwent201T1 rest-injection and99mTc-tetrofosmin. baseline-postnitroglycerin (0.4 mg sublingually) SPET studies, within 48 h. Tomograms based on the three spatial planes were divided into 15 segments and regional tracer uptake was quantitatively analysed. Viability was defined as presence of tracer uptake >50% of peak activity on baseline studies or after reversibility. The percentage of peak activity of99mTc-tetrofosmin at baseline correlated with that of 201T1 (r=0.82,P <0.001). On baseline99mTc-tetrofosmin studies, 73 of the 225 segments that were analysed had <50% of peal. activity. Fifteen percent of these segments showed reversibility after nitrate administration, with an increase in99mTc-tetrofosmin uptake from 40%±9% to 57%±9% of peak activity (P=0.003). All reversible segments after nitrate administration had viability criteria on201Tl studies, but 20 segments that were non-viable on99mTc-tetrofosmin. studies were viable on201Tl studies. Using a threshold value of >40% of peak activity, only seven segments remained non-viable on99mTc-tetrofosmin studies. Overall agreement between99mTc-tetrofosmin with nitrates and201Tl-reinjection regarding the presence of myocardial viability was 90%. Detection of myocardial viability with99mTc-tetrofosmin. was enhanced after nitrate administration, correlating with viability criteria observed on thallium studies.