Gustavo Torres

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.

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.

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.

Bone pain palliation with strontium-89 in breast cancer patients with bone metastases and refractory bone pain

Fifteen patients with breast cancer and skeletal metastases who had bone pain refractory to opioid analgesics and who were not eligible for or had not responded to local field radiotherapy, were treated with strontium-89. All patients had received previous treatment with chemotherapy and radiotherapy for bone metastases. Severity of bone pain, sleeping pattern, mobility and dependency on analgesics were evaluated before and 4, 8 and 12 weeks after89Sr administration. Patients received 2 MBq/kg (118–148 MBq) of89Sr by i.v. injection. Pain relief and a reduction in analgesic requirements were observed in 7 of the 15 (47%) patients, with a reduction in the severity score from 34% to 71%. Duration of the response varied from 3 to 7 months. A decrease in peripheral blood cell count was observed in 11 patients: a 15%–66% reduction in white cell count and a 14%–75% reduction in platelet count were detected at 12 weeks after treatment in these patients. We conclude that89Sr is effective (47% response rate) for bone pain palliation in patients with bone metastases from breast cancer. Dependency on opioid analgesics may be reduced in patients with refractory bone pain.

Polyclonal 111In-IgG, 125I-LDL and 125I-endothelin-1 accumulation in experimental arterial wall injury

To test iodine-125 labelled low-density lipoprotein (125I-LDL), polyclonal indium-111 labelled immunoglobulin G (111In-IgG) and iodine-125 labelled endothelin-1 uptake in metabolically active atheromatous plaques after arterial wall injury, we performed balloon de-endothelialization of carotid arteries or abdominal aortas in 24 New Zealand male rabbits which were fed with a normal diet (n=14) or a hypercholesterolaemic diet (n=10) after surgery. Six weeks later the animals were injected with 200 μCi of (125I-LDL), and/or with 100 μCi of 111In-IgG or with 9 μCi of 125I-endothelin-1. Forty-eight hours later the animals were sacrificed. Carotid arteries and aortas were removed, counted and fixed for autoradiography and light microscopy examination. Contralateral carotid arteries and thoracic aortas served as controls.Significant 111In-IgG uptake was observed in the injured arteries at autoradiography, with localization mainly in the healing edges, and at well counting. The percentage of the injected dose per gram (%D.inj/g) was 0.0188±0.06 versus 0.0059±0.003 in controls (P< 0.05). There was no difference in 111In-IgG uptake between arteries with injury alone and those with active atheroma formation at the site of the injury. Significant (125I-LDL), uptake was observed only when lipid deposition was present at light microscopy (%D.inj/g of 0.0024±0.0005 vs 0.0010±0.0003 in controls, P < 0.05). 125I-endothelin-1 accumulation was observed in four of five injured aortas both at autoradiography, with diffuse localization, and at well counting (%D.inj/g of 0.0012±0.0004 in the abdominal aortas vs 0.0008±0.0003 in the thoracic aortas).Polyclonal IgG may accumulate in injured arteries without active atheroma formation. Inflammatory reaction at the site of the injury may cause 111In-IgG uptake independently of atheromatous plaque formation. LDL accumulation takes place only with active atheroma formation at the site of the injury. Use of labelled peptides such as endothelin-1 may provide further insight into the mechanisms of atheromatous plaque formation.

Individual renal function based on 99mTc dimercaptosuccinic acid uptake corrected for renal size.

BackgroundDecreased relative 99mTc dimercaptosuccinic acid (99mTc-DMSA) uptake can be a consequence of abnormal kidney size, associated with normal or impaired function. When there is a small kidney, relative 99mTc-DMSA uptake is decreased, and it is sometimes difficult to distinguish a small, normal kidney from a hypofunctioning kidney. Here, relative renal function was studied by quantifying the relative 99mTc-DMSA uptake corrected for renal size (RCU). MethodsFive hundred and fifty-five consecutive patients (184 adults) aged 1 month to 82 years (mean, 14.8 years) underwent a 99mTc-DMSA study for various renal diseases. Results were compared with the relative 99mTc-DMSA uptake without size correction (RUU). Visual evaluation of images was also performed. ResultsIn 288 patients (52%) the relative 99mTc-DMSA uptake was normal, either uncorrected or corrected, for renal size; in 184 (33%) it was abnormal by both quantification methods; and in 83 (15%) it was abnormal only by one method. Two hundred and fifty-seven patients (46%) presented with decreased RUU in one kidney, associated with a small kidney in 73 patients (13%). RCU was normal in all of these 73 patients (100%, P<0.0001). The sensitivity and specificity of RCU for evaluating renal function in relation to small renal size and with respect to RUU were 72% and 97%, with positive and negative predictive values of 95% and 80%, and an accuracy of 85%. Visual analysis of the 73 studies with decreased RUU and normal RCU showed a small, normal kidney on 55 occasions (75%), cortical scars in eight (11%), and impaired bilateral function in 10 (14%). Visual analysis of 10 studies with normal RUU and decreased RCU showed dilated pyelocalyceal system in seven occasions (70%) and normal kidneys in three (P<0.0001). ConclusionIt is concluded that relative 99mTc-DMSA uptake corrected for renal size is a more accurate method for assessing individual renal function. When there is a small kidney, relative 99mTc-DMSA uptake corrected for renal size can distinguish between a normal and a hypofunctioning kidney.

Antigranulocyte Antibody Bone Marrow Scans in Cancer Patients with Metastatic Bone Superscan Appearance

In clinical practice, it may be difficult to distinguish a metastatic bone superscan appearance from a normal bone scan. To determine if assessment of bone marrow is helpful in the diagnosis of bone invasion in patients with suspected bone superscans, the authors performed antigranulocyte antibody bone marrow scans in 10 consecutive cancer patients who had a conventional bone scan interpreted as metastatic superscan appearance. All patients presented with bone marrow scans showing marked absence of tracer uptake in the central skeleton suggesting tumour replacement. Laboratory tests showed decreased peripheral blood cells in 9 patients. Bone radiographs showed metastatic involvement with diffuse osteoblastic lesions in 9 patients. Antigranulocyte bone marrow scans show extensive bone marrow invasion in cancer patients with suspected bone superscans. This result reinforces the concept of these patients having extensive bone invasion despite mild abnormalities in the bone scan. Confirmation of extensive bone invasion on patients with suspected bone superscans may contribute to a proper staging of these patients.

Preexisting human anti-murine antibodies and the effect of immune complexes on the outcome of immunoscintigraphy

Radiolabeled monoclonal antibodies (MoAb) are useful in radionuclide imaging. Human anti-murine antibodies (HAMA), however, could produce immunologic effects or alter the outcome of immunoscintigraphy. Three patients are reported who had been exposed previously to radiolabeled MoAbs and in whom subsequent immunoscintigraphy was performed. All patients showed abnormat biodistribution of the antibody and increased hepatic uptake. Human anti-murine antibody was demonstrated in all patients. These results indicate that immune complexes are formed after HAMA-MoAb reaction and are then phagocytosed by cells of the reticuloendothellal system.

Antigranulocyte bone marrow scans in Paget's disease.

Pagets disease of bone is a disorder of bone remodeling in which excessive production of structurally abnormal bone occurs, with the primary and fundamental abnormality residing in the osteoclast. To evaluate further the jeopardized bone marrow in Pagets disease, the authors studied 29 skeletal lesions by means of conventional bone imaging and antigranulocyte antibody bone marrow imaging in eight consecutive patients affected by Pagets disease. Bone scans showed abnormal tracer uptake in the 29 skeletal sites (11 pelves, 10 vertebrae, 5 extremities, 2 skulls, and 1 rib). Antigranulocyte antibody bone marrow scans showed decreased uptake of radiopharmaceutical in 16 (55%) of those 29 areas (8 pelves, 7 vertebrae, and 1 rib). Lesions appeared to be more extensive on bone scans than on bone marrow scans. It was concluded that antigranulocyte bone marrow scans may show focal defects in hematopoietic bone marrow in patients with Pagets disease. Pagets disease affects the cortical bone more severely than the bone marrow.

111in-Polyclonal IgG and 125I-LDL Accumulation in Experimental Arterial Wall Injury

Atherosclerosis is a main cause of morbidity and mortality. Standard imaging techniques such as CT scanning, magnetic resonance imaging, ECO-DOPPLER, and angiography are inneffective to detect atheromatous plaques in early stages of developement, when the lesions are most metabolically active and medical interventions could be beneficial. There is therefore a clinical need to develop a noninvasive method that could assess the presence and the extension of atherosclerotic disease in patients in monitoring treatment.