Scintigraphic imaging of breast cancer: a review

Scintimammography is a recently verified technique that will expand the use of nuclear medicine to a new group of patients in whom scintigraphic imaging has not been widely used. If performed correctly, and in certain groups of patients, it delivers a sensitivity as high as X-ray mammography or magnetic resonance imaging (MRI) in palpable tumours but with greater specificity. It is best used in patients in whom X-ray mammography, ultrasound and MRI prove non-diagnostic or unhelpful, particularly those women with dense breasts or who have had previous breast surgery. The mechanism of uptake of 99Tcm-MIBI in breast tissue is only partly understood and in itself may help in determining important aspects of tumour function, such as the response to cytotoxic chemotherapy. Other scintigraphic methods for imaging breast cancer may be able to look at other aspects of cancer function, for example blood supply, metabolic rate or the in vivo assessment of oestrogen or somatostatin receptor status. This in turn may be useful in planning treatment. Metastatic disease may best be monitored with 18F-FDG PET, which has a sensitivity greater than MRI but a similar specificity. Much furtner work will need to be done on the use of nuclear medicine in breast cancer, but the addition of unique functional information to the anatomical data from X-ray and MRI should benefit future patients' management.     

The development of x-ray imaging to study renal function

The well-established role of the kidney in control of blood volume and ultimately arterial blood pressure has been underscored by the demonstration of alterations in renal hemodynamics and function recognized as responsible for these and other regulatory mechanisms. Nevertheless, the spatial complexity of intrarenal structure and function has made evident the need to study these separately in different regions of the intact kidney. Because of the introduction of x-rays, assessment of renal function has indeed been one of their attractive applications. However, despite the appeal of their noninvasiveness, several limitations confounded the different x-ray techniques used, most of which remained unresolved until the development of computed tomography. Furthermore, the development of fast imaging, which allows repetitive analysis of the same region of interest during the transit of contrast medium, holds a great potential to estimate intrarenal distribution of blood flow and the dynamic characteristics of tubular fluid flow in individual nephron segments. This latter assessment requires the administration of filterable x-ray contrast medium, which is cleared from the plasma almost exclusively by glomerular filtration, and the generation of contrast dilution curves. A historical review of the development and progress of the various x-ray techniques used will help understand the past and present of x-ray imaging, and will make it easier to envision the importance of their future roles in the study of renal physiology and pathophysiology.     

Scintigraphic imaging of pituitary adenomas: an in vivo evaluation of somatostatin receptors

We have performed pituitary scintigraphy with the somatostatin (SS) analog pentetreotidean by (111In-P) in patients with GH-secreting adenoma or with "clinically non functioning" adenoma (NFA) to evaluate the presence and the functionality of SS receptors (SS-R). 111In-P pituitary accumulation was expressed as Activity Ratio (AR): the ratio between the uptake of radioactivity by the adenoma and that of the normal brain tissue. In subjects without pituitary disease, AR ranged from 1.6 to 2.2 and a value lower than 2.2 was thus arbitrarily considered as normal. In 15 out of the 17 patients with GH-secreting adenoma, an accumulation of the radioligand was shown. Median AR was 3.8 (range 1-6.9; in 14 AR were greater that 2.2) and ARs were directly correlated (r = 0.54; p < 0.05) with the suppressibility of plasma GH levels by octreotide (OC) acute administration. In two patients who repeated scintigraphy during chronic OC treatment, AR values were reduced. In all the 22 patients with NFA an accumulation of 111In-P at the pituitary level was observed and median AR was 3.0 (range 1.5-20; in 14 greater that 2.2). In vitro autoradiography of surgical specimens in 6 NFA patients revealed SS-R in 4 cases with high scintigraphic AR and negative results in two cases with low AR. Scintiscan was repeated during chronic OC treatment in 5 patients with high score: AR decreased in one patient, increased in three, and did not change in the other patient. No changes in tumor size were shown in any of these patients. A total of 8 patients (3 GH secreting and 5 NFA) had "normal" AR values. CONCLUSIONS: In acromegaly scintigraphy with 111In-P visualizes functioning pituitary SS-R coupled to intracellular events that control hormonal hypersecretion and tumor growth. In contrast, in spite of the positivity of 111In-P imaging in most patients with NFA, their receptors might have a defect in the coupling-transduction process, as they are not inhibited by OC treatment and no tumor shrinkage is observed.     

Neural control of renal function

The renal nerves are the communication link between the central nervous system and the kidney. In response to multiple peripheral and central inputs, efferent renal sympathetic nerve activity is altered so as to convey information to the major structural and functional components of the kidney, the vessels, glomeruli, and tubules, each of which is innervated. At the level of each of these individual components, information transfer occurs via interaction of the neurotransmitter released at the sympathetic nerve terminal-neuroeffector junction with specific postjunctional receptors coupled to defined intracellular signaling and effector systems. In response to normal physiological stimuli, changes in efferent renal sympathetic nerve activity contribute importantly to homeostatic regulation of renal blood flow, glomerular filtration rate, renal tubular epithelial cell solute and water transport, and hormonal release. Afferent input from sensory receptors located in the kidney participates in this reflex control system via renorenal reflexes that enable total renal function to be self-regulated and balanced between the two kidneys. In pathophysiological conditions, abnormal regulation of efferent renal sympathetic nerve activity contributes significantly to the associated abnormalities of renal function which, in turn, are of importance in the pathogenesis of the disease.     

Torsion of intraperitoneal renal transplants: imaging appearances

OBJECTIVE: Torsion of a renal transplant is a rare complication with nonspecific clinical manifestations. Prompt detection is necessary to allow surgical treatment and to preserve renal function. We describe the radiologic appearances of torsion of intraperitoneal renal transplants in patients who have undergone simultaneous renal and pancreatic transplantation or dual renal transplantation. CONCLUSION: Renal transplant torsion should be suspected when a change in renal axis associated with abnormal perfusion occurs in an intraperitoneal kidney.     

Scintigraphic assessment of silent myocardial ischaemia after early infarction using myocardial SPET imaging with 201Tl and 123I-MIBG

To test the hypothesis that myocardial sympathetic denervation reflects silent myocardial ischaemia early after infarction, 12 patients with myocardial infarction but without post-infarction angina pectoris underwent single photon emission tomography (SPET) at rest with 201Tl and 123I-metaiodobenzylguanidine (MIBG) shortly after and 3 months after infarction. Short-axis SPET images at the basal, mid-ventricular and apical portions of the left ventricle were selected, and each short-axis image was divided into eight segments. Tracer uptake in each of the 24 segments was scored using a 4-point scale. The total score in each segment was calculated as the defect score for each image, and the difference between the total defect score for the 201Tl and 123I-MIBG images was calculated as the delta defect score. All 12 patients underwent exercise stress 201Tl scintigraphy 1 month after infarction, and they were divided into two groups: those patients with (Group A, n = 7) and those patients without (Group B, n = 5) transient perfusion defects in the peri-infarcted region without chest pain. For the 123I-MIBG defect score, a marked reduction at 3 months was observed in Group A (24 +/- 12 vs 13 +/- 6; P < 0.01), whereas the defect score remained unchanged in Group B (25 +/- 7 vs 23 +/- 8; N.S.). The delta defect score was significantly reduced in Group A (10 +/- 5 vs 6 +/- 4; P < 0.05), whereas it remained unchanged in Group B. The 123I-MIBG defect score early after infarction was higher than the exercise-induced 201Tl defect score (24 +/- 12 vs 20 +/- 9; P < 0.01), whereas at 3 months post-infarction it was lower than the exercise-induced 201Tl defect score (13 +/- 6 vs 20 +/- 9; P < 0.05). Moreover, effort chest pain during daily activities was noted in 5 of the 7 (71%) patients in Group A within 3 months post-infarction. The results of this study suggest that viable but denervated myocardium (mismatched 123I-MIBG defects) is present in peri-infarcted regions, and that myocardial sensory nervous disturbance, which may co-exist with sympathetic nervous denervation, may induce silent myocardial ischaemia in patients with myocardial infarction.     

Changes in renal function with aging

The epidemiology, clinical course, response to treatment, and ultimate outcome of essential hypertension vary as a function of gender. Three early trials on hypertension reported an increase in all-cause mortality in treated white women compared with black women or with men of both races. Later studies, however, suggest that drug therapy has similar and beneficial effects in hypertensive men and women. Women may tolerate hypertension better than do men. Diastolic hypertension correlates with higher mortality from coronary artery disease in men than in women. Special considerations apply to treating the hypertensive woman. Use of oral contraceptives may precipitate or accentuate the problem. In contrast, in the postmenopausal female, estrogen replacement may actually improve hypertension, via several mechanisms. These include the impact of the hormone on vasomotricity, its enhancement of baroreceptor sensitivity, and its impact on the hyperinsulinemia characteristic of menopause. Treatment of hypertension must be individualized with respect to gender. More data on the consequences of treatment of women with hypertension are needed, particularly longterm studies to assess the impact of treatment on mortality.     

Scintigraphic evaluation of experimental colitis in rabbits

Scintigraphic techniques are frequently used for evaluation of inflammatory bowel disease. The radiopharmaceutical of choice is labeled leukocytes. In this study, two new agents, 111In-labeled polyethylene glycol-coated liposomes and 111In-labeled human nonspecific gamma globulin (immunoglobulin G; IgG), were compared with 111In-leukocytes in a rabbit model of colitis. METHODS: In rabbits, acute colitis was induced by colonic instillation of trinitrobenzene sulfonic acid at 25 cm from the anal sphincter. After 24 hr, 15 MBq of the radiopharmaceuticals was injected intravenously in groups of four rabbits. Twenty-four hours after injection, the animals were killed and macroscopic abnormalities were scored in seven consecutive affected colonic segments of 5 cm each (0 = normal, 1 = inflammation, 2 = ulcers). The ex vivo uptake was measured in the normal ascending colon and the affected colonic segments. The colitis index (CI, affected-to-normal colon-uptake ratio) was calculated. RESULTS: Histologically, an acute, patchy, transmural colitis was observed at the site of instillation and the distal colon. The CI of all agents in colitis lesions correlated with the severity of the abnormalities. With increasing severity, the CI for liposomes was 1.86 +/- 0.24, 4.88 +/- 0.42 and 7.42 +/- 0.54 (r2 = 0.68, p < 0.001); for leukocytes 1.77 +/- 0.32, 3.10 +/- 0.58 and 5.54 +/- 0.83 (r2 = 0.31, p < 0.01); for IgG 1.60 +/- 0.29, 2.81 +/- 0.21 and 2.65 +/- 0.21 (r2 = 0.29, p < 0.02). CONCLUSION: Indium-111-labeled-leukocytes, -IgG and -liposomes all show increased uptake in inflamed colonic tissue. Indium-111-liposomes showed the highest CI, which correlates best with the morphological abnormalities. Indium-111-leukocytes and 111In-liposomes are superior to 111In-IgG for this indication.     

Advances in the imaging of renal infection. Helical CT and modern coordinated imaging

Traditionally, imaging of renal infections was largely through a multimodality approach. Excretory urography, ultrasonography, nuclear scintigraphy, and CT all played major roles; however, in recent years, CT has increased in prominence in the imaging and evaluation of renal infection. Part of the reason for this trend includes improvements in the availability of CT scanners and more timely access to them. Helical scanning technology has also greatly increased the quality and usefulness of the information CT provides. Most uncomplicated cases of acute renal infection in adults do not require imaging for diagnosis and treatment. When imaging is indicated, however, contrast-enhanced CT almost always is the study of choice. For cases in which renal calculi may be present, the study should also include noncontrast images through the kidneys.     

Role of the donor in post-transplant renal function

BACKGROUND: The donor, i.e. adult or paediatric, might influence the outcome of the graft function. METHODS: The glomerular filtration rate (GFR) of 120 transplanted children (47 girls) aged 10.4+/-4.6 years (0.7-17.2) was prospectively assessed over a 5-year period. The patients were divided into two groups according to the age of donor: adult (donor age > 18 years; n=33) and paediatric (donor age < 18 years; n=87). GFR was assessed by inulin clearance at 3, 6 and 12 months and yearly thereafter. RESULTS: The average GFR was stable in the range of 70 ml/min/1.73 m2 for the whole follow-up period. The adjusted GFR in adult graft recipients was significantly higher at 3 months post-transplantation: 80.6+/-36.9 vs 65.1+/-22.0, P=0.02. However, from the second year post-transplantation, the adjusted GFR in paediatric graft recipients became significantly higher than that of adult graft recipients. Such results could be due to an improvement in the absolute GFR (ml/min) of paediatric graft recipients with time (P=0.0001) whereas that of the adult graft recipients remained stable despite the children's growth. CONCLUSIONS: The adjusted GFR of adult graft recipients was significantly higher than that of paediatric graft recipients in the early post-transplant period. In the long-term, a progressive decrease in adjusted GFR was noted in adult graft recipients. On the one hand, this may be due to a functional adaptation and/or inadequate compensatory growth of the graft. On the other hand, the absolute GFR of paediatric graft recipients increased, suggesting an ongoing capacity for growth and/or compensatory hypertrophy after child-to-child renal transplantation.     

Changes in renal function associated with indinavir

BACKGROUND: Indinavir use is associated with a spectrum of renal and urinary tract complications including nephrolithiasis, renal colic and pain without recognizable lithiasis, and a picture of crystalluria-dysuria. A frank nephropathy has not been recognized as part of the spectrum. METHODS: A retrospective analysis of 106 HIV-infected individuals receiving indinavir was performed with the purpose of identifying the frequency and risk factors for indinavir-associated nephropathy and urinary complications. Individuals receiving ritonavir or nelfinavir served as controls. RESULTS: A sustained elevation of creatinine (>20%, into abnormal range) was identified in 20 (18.6%) subjects treated with indinavir but not with other protease inhibitors. Creatinine elevation was associated with treatment duration of more than 54 weeks [odds ratio (OR), 7.1; 95% confidence interval (CI), 1.8-27.7], low baseline body mass index < or = 20 kg/m2 (OR, 4.0; 95% CI, 1.0-16.6), and use of trimethoprim-sulphamethoxazole (TMP-SMX; OR, 4.6; 95% CI, 1.5-13.8). Lower urinary specific gravity (P = 0.015), and leukocyturia (P<0.001) were frequently associated features of indinavir nephropathy. No patient developed severe renal impairment and abnormalities were reversible upon discontinuation of the drug. Complications (renal colic, or pain and dysuria) occurred after a mean of 36 weeks (95% CI, 23-48) of indinavir treatment in 13 subjects (12.3%), eight of whom (62%) presented elevated creatinine during follow-up. Only long-term exposure to TMP-SMX (>160 weeks) was identified as a potential risk for the occurrence of a clinical event (OR, 4.7; 95% CI, 1.2-19.2). CONCLUSIONS: A crystal nephropathy, characterized by serum creatinine elevation, loss of concentrating ability of the kidney, leukocyturia, and renal parenchymal image abnormalities, is a frequent complication of indinavir therapy. Identification of individuals at risk, particularly those with low body mass index or receiving TMP-SMX prophylaxis, may help the decision to initiate indinavir or chose an alternative protease inhibitor in order to minimize renal and urinary tract adverse events.     

Scintigraphic visualization of pulmonary thrombi with 123I-YPACK-TNK-tPA

BACKGROUND: We have previously demonstrated that radiolabeled tissue-type plasminogen activation (tPA) in which the plasminogen-activating catalytic site has been inactivated binds avidly to thrombi and can be used for scintigraphic detection of pulmonary thrombi in vivo. The present study was performed to overcome identified limitations of the initially developed approach and to determine whether a tracer made with a molecular variant of tPA, TNK-tPA, would provide superior images of pulmonary thrombi and hence facilitate differential diagnosis of pulmonary embolism from acute myocardial infarction. It was thought that TNK-tPA may be superior in view of its longer biological half-life and less avid uptake by macrophages that would otherwise contribute to high background because of non-clot-selective uptake of the tracer. METHODS: 123I-tyrosylprolylarginyl chloromethyl ketone (123I-YPACK-TNK-tPA) was infused into the systemic circulation of dogs with either pulmonary or right ventricular thrombi induced with thrombogenic tips of modified guide wires. Planar and single-photon emission computed tomography (SPECT) scintigraphic data were obtained, and blood and tissue samples were acquired for analysis of the distribution of the radiotracer over time. RESULTS: Tracer cleared from blood with an alpha phase half-life of 10 +/- 1 min, paralleling the clearance of unlabeled TNK-tPA. Only minimal release of labeled fragments from liver into blood occurred during the entire time course of the imaging studies. Pulmonary thrombi were visualized with SPECT within 30-120 min in all dogs. Images were superior to those obtained after infusion of labeled wild-type tPA, primarily because of diminished background radioactivity and consequently increased scintigraphic contrast. In one dog which had a right ventricular thrombus, the thrombus was readily detectable in both planar and SPECT images. CONCLUSIONS: Radiolabeled TNK-tPA in which plasminogen-activating activity has been inhibited biochemically is an excellent radiopharmaceutical for prompt scintigraphic detection of pulmonary and ventricular thrombi in vivo, and an attractive candidate for rapid, sensitive and non-invasive diagnosis of pulmonary thromboembolic disease in patients.     

Relationship between blood pressure and renal function

RENAL DAMAGE CAUSED BY HYPERTENSION: Renal vasoconstriction seems to be a key factor in the origin of arterial hypertension and accounts for the decrease in renal blood flow commonly observed in patients with hypertension. An inverse correlation has been found between renal blood flow and clinic blood pressure levels in established hypertension. Other features of renal damage attributable to high blood pressure have also been correlated with clinic blood pressure levels. Microalbuminuria is a good example of an alteration in renal function that depends in part on blood pressure levels. EFFECTS OF ANTIHYPERTENSIVE AGENTS: Antihypertensive agents can prevent or ameliorate renal vascular damage secondary to arterial hypertension, including renal failure. Ambulatory blood pressure monitoring is an excellent method of studying blood pressure levels in relation to end-organ damage and the blood pressure response to antihypertensive agents. Preliminary studies using this technique indicate that changes in renal function are closely correlated with the average daily blood pressure in arterial hypertension. CONCLUSIONS: Further studies are needed on the mechanisms of renal deterioration and on how to preserve renal function in arterial hypertension.