Diagnostic value of bone and Ga-67 imaging in skeletal tuberculosis

In the future, U.S. military forces will be faced with opposing forces that have chemical and biological weapon capabilities. Although drugs used against these agents would be an ideal solution to protecting soldiers, the ability to test their efficacy in humans is limited by several ethical and technical problems: (1) the high risk of toxicity to volunteers; (2) the risk of delayed side effects in the volunteers; and (3) the inability to extrapolate effects against sublethal doses to efficacy against lethal doses. The Food and Drug Administration (FDA) relies on safety and efficacy data in humans, making approval for these types of drugs difficult. An alternative approach for regulatory approval would be to use surrogate markers. Surrogate markers are biochemical or physiologic measurements that demonstrate the direct effect of the drug. Surrogate markers, such as CD4 counts and viral RNA levels, have been used recently in the anti-human immunodeficiency virus drug approval process with success. A drug development program using surrogate markers must meet several criteria, including demonstrated efficacy in animal models, correlation between efficacy and the surrogate marker, a link between the surrogate marker and the pathophysiology and toxicologic effects of the agent, and the ability to produce the surrogate marker in humans. This article illustrates the use of drug-induced methemoglobin as a surrogate marker for protection against cyanide intoxication. Safety issues regarding this class of drugs would also have to be pursued aggressively during and after their use by military forces. Demonstrating that the drug satisfies these criteria would be a platform for approval by the FDA. The guidelines mentioned above should be an acceptable approach for FDA approval, scientific researchers, medical practitioners, and the soldiers using these drugs.     

SLE myocarditis. Detection by Ga-67 citrate scintigraphy

Cardiac uptake of Ga-67 in myocarditis has been described in association with a number of disease entities. However, there are no reports in the current literature describing Ga-67 uptake in myocarditis due to systemic lupus erythematosus, a disease that often involves the heart. The authors present the case of a patient with a long history of systemic lupus erythematosus in whom new ECG changes and left ventricular wall motion abnormality developed, and who demonstrated significant global myocardial uptake on Ga-67 scintigraphy. Other etiologies including myocardial infarction, epicardial coronary disease, pericarditis, endocarditis, dilated cardiomyopathy, and viral infection were excluded during extensive work-up.     

Iodine-123 BMIPP and Ga-67 scintigraphy in liposarcoma

Post-concussion symptoms (PCS) (such as headaches, irritability, anxiety, dizziness, fatigue and impaired concentration) are frequently experienced by patients who have sustained a minor head injury (MHI). The post-concussion syndrome has been defined as a clinical state where 3 or more symptoms persist for more than 3 months. This report focuses on the quantification of PCS according to the Rivermead Postconcussion Symptoms Questionnaire (RPQ). We studied 100 consecutive patients with MHI and normal computed tomography of the brain. At 3 months after injury, 62% reported the presence of one or more symptoms, and 40% fulfilled the diagnostic criteria for post-concussion syndrome. Patients with post-concussion syndrome had significantly (P < 0.001) higher RPQ scores (mean 19.1, SD 11.9) than those without (mean 1.2, SD 1.8). Patients on sick leave owing to the injury reported significantly (P = 0.05) higher RPQ scores (mean 10.3, SD 13.2) than those not on sick leave (mean 5.5, SD 8.6). We observed no association between age, gender, cause of injury, severity of injury, duration of amnesia and RPQ score. RPQ score provides useful information about the severity of PCS regardless of whether the diagnostic criteria for the post-concussion syndrome are met or not.     

Lactoferrin: its role as a Ga-67-binding protein in polymorphonuclear leukocytes

Gallium-67 bound to lactoferrin--an iron-binding protein found in high concentration in polymorphonuclear leukocytes--has been isolated from PMNs that have previously been incubated with Ga-67 citrate. Although the cell-labeling efficiency was highly variable (0.026-10%), much of the activity that did bind to the PNMs (74.8 +/- 10%) was recovered in the supernatant after sonication and centrifugation. About half (approximately 47%) of the PMN-bound activity was retained after dialysis and was presumably bound to macromolecules in the supernatant. When this retained activity was placed on a column containing immobilized antilactoferrin antibody, almost three quarters of the activity was bound to the column. This bound activity was (36 +/- 17%) of the total activity absorbed by the PMN. The addition to the antilactoferrin column of a known antigen-antibody-dissociating agent caused the disolution of the complex. No significant activity was bound to a control column. The findings indicate that lactoferrin is a major Ga-67-binding protein present in PMNs and suggest that it may play a major role in Ga-67 localization in an abscess. These results support the contention that molecules binding ferric iron have an important effect on Ga-67 distribution in vivo.     

Kawasaki disease

We analysed the cytoskeletal proteins and extracellular matrix components of in vitro cultured BMSC both in resting state and after activation with IFN gamma and TNF alpha, using an immunoperoxidase procedure. BMSC expressed fibronectin, alpha-actin, beta-tubulin, vimentin and vinculin while cytokeratinpan, GFAP, neurofilament, desmin and laminin were not expressed. This pattern of expression was not affected by addition of TNF alpha and IFN gamma, but differs from human tonsil stromal cells for laminin expression and alpha-actin localization.     

Kawasaki disease

This study was conducted to investigate the functional and morphological aspects of orthotopic lung xenograft rejection in a concordant hamster-to-rat donor-recipient species combination. By postoperative day (POD) 3, allotransplanted grafts demonstrated good aeration, but infiltrates were seen in all the xenotransplanted lungs. Antihamster lymphocytotoxic antibody titers increased to 5.2 +/- 1.1 by POD 3 (P < 0.05 vs POD 1) and reached 7.0 +/- 0.8 by POD 5 (P < 0.05 vs PODs 1 and 3). The CD4+/CD8+ ratio in peripheral blood lymphocytes increased significantly on POD 3 (P < 0.05 vs untransplanted), but decreased by POD 5 (P < 0.05). Histologically, on POD 3 the xenotransplanted grafts were characterized by perivascular cellular infiltrates and edema. Cytologically, the cells consisted of small round lymphocytes, monocytes, and occasional neutrophils. Immunohistochemical analysis showed heavy IgM and C3 deposits in the vascular endothelium, without any IgG deposits. Allotransplanted grafts showed moderate W 3/25 + (28.3 +/- 17.3%) and MRC OX8 + (38.7 +/- 0.7%) cellular infiltrations on POD 3, but ED1 + (8.0 +/- 3.7%) cells were rare. Conversely, in the xenotransplanted grafts, ED1 + (34.2 +/- 16.4%) cells were more prevalent than MRC OX8 + (18.1 +/- 16.5%) cells on POD 3, at P < 0.01 and P < 0.05 vs allograft, respectively. These results indicate that both antidonor antibodies and macrophages/monocytes play an important role in the concordant lung xenograft rejection.     

Ga-67 scan as a prognostic indicator in primary lung carcinoma

GA-67 scintigraphy was performed on 74 patients with a variety of histologic types of untreated primary lung carcinoma. Ga-67 uptake was determined, allowing for differences in tumor size. Ga-67 uptake was compared with the response to the incidence of metastases, and to host survival in the 74 patients. From these results, it is suggested that the greater the Ga-67 accumulation in the tumor, the higher the incidence of metastases and the shorter the host survival. Ga-67 scintigraphy appears to be a valuable tool in indicating the prognosis following radiation therapy in patients with primary lung carcinoma.     

Accumulation of Tc-99m MIBI in breast lymphoma: comparison with Ga-67 citrate

We report 2 cases of malignant lymphoma of the breast which were clearly shown on total body imaging as well as on SPECT with Ga-67 and Tc-99m MIBI. Tumor accumulation of Ga-67 was seen in all cases including a recurrent tumor. Ga-67 scintigraphy is useful for follow up in detecting relapse, as well as in predicting responses to therapy. Tc-99m MIBI was found to accumulate in the malignant lymphoma of the breast, and especially SPECT images of breast lesions provided better contrast than planar images, and Tc-99m MIBI SPECT could diagnose localization of the tumor because there was no uptake by the breast. But the Tc-99m MIBI accumulation of the tumor was lower than Ga-67.     

Functional imaging of Hodgkin's disease with FDG-PET and gallium-67

We report a case of Hodgkin's lymphoma (Stage I B) which was studied using Ga-67-scintigraphy as well as whole body FDG-PET. Ga-67-scintigraphy detected a slightly increased uptake in the paraaortic and pelvic lymph nodes. However, FDG-PET was able to localize a much larger number of affected foci with a high glucose utilization rate in the right and left paraaortal regions, in the middle of the epigastrium, in the right and left parailiacal regions and one focus in the left upper mediastinum. Our experiences give rise to the assumption that FDG-PET ist significantly superior to gallium scintigraphy in Hodgkin's disease. Whole body FDG-PET can result in an upstaging of the patient and has therefore a major impact on the therapeutic management.