Abnormal gallium-67 skull uptake: a sign of peripheral marrow activation in HIV-positive patients with disseminated mycobacterioses

The purpose of this study was to investigate the significance of abnormal 67Ga-citrate skull uptake in AIDS patients with mycobacterioses. METHODS: Gallium-67 scans of 39 HIV-positive patients who have been diagnosed with mycobacterioses were analyzed; the scans of 15 consecutive HIV-positive patients without mycobacterioses were also reviewed as a control group. The skull was chosen to assess bone marrow uptake because of the absence of overlapping structures. RESULTS: Twenty-nine of 39 (74%) patients with mycobacterial infections had disseminated disease. Gallium-67 uptake in the skull was visualized in 24 of these 29 patients (82%). One of the patients without disseminated disease and one patient in the control group (n = 15) showed skull uptake. CONCLUSION: Abnormal 67Ga skull uptake appears to be a sensitive (82%) and specific (82%) indicator of disseminated mycobacterial infection in HIV-positive patients.     

99mTc-citrate versus 67Ga-citrate for the scintigraphic visualization of inflammatory lesions

Citric acid was labeled with 99mTc with an efficiency of > 99%. The biodistribution of 99mTc-citrate was studied in mice with turpentine-induced abscesses in comparison to 67Ga-citrate. The max. abscess/muscle concentration ratios were 4.61 +/- 1.92 (3 h) for 99mTc-citrate and 4.76 +/- 2.04 (4 h) for 67Ga-citrate. Arthritis was induced in 10 rabbits by intra-articular injection of ovalbumin Scintigrams obtained 4 days later and at 3 h post-injection of 99mTc-citrate showed increased activity involving the synovium. The max. arthritic/contralateral knee ratio was 3.19 +/- 1.29 (3 h) and 6.47 +/- 3.71 (24 h) for 99mTc- and 67Ga-citrate, respectively. The blood clearance curve of 99mTc-citrate in rabbits was biexponential with a fast (T1/2 = 36 min) and a slow (T1/2 = 18 h) component, compared to mono-exponential clearance of 67Ga-citrate (T1/2 = 23 h). In 10 patients with rheumatoid arthritis whole-body scintigrams and spot images of involved joints indicated localization of the tracer in inflamed tissues. The mean target-to-soft tissue ratios were 3.04 +/- 0.81 and 4.95 +/- 2.56 for 99mTc-citrate and 99mTc-MDP, respectively. Renal clearance of radioactivity was evident from the scintigrams. Our results demonstrated that 99mTc-citrate is effective as a radiopharmaceutical for the visualization of inflammatory lesions and may be preferred to 67Ga-citrate due to the ideal physical characteristics of the radionuclide, easy preparation, low cost, early accumulation and the preference for the renal route of excretion.     

Lung inflammation in patients with systemic lupus erythematosus detected by quantitative 67Ga-citrate lung scanning

The severity of lung inflammation in 34 patients with systemic lupus erythematosus (SLE) was measured by quantitative 67Ga-citrate lung scanning. The severity of lung inflammation in SLE was represented by the 67Ga uptake index (GUI). Quantitative 67Ga lung scanning was also performed on 20 normal controls for comparison with the SLE patients. The patients were divided into two subgroups according to the following two criteria: (a) stable or flare stage according to clinical features; or (b) positive or negative results of chest X-ray. The GUI values of the subgroups were also compared. The results revealed a trend towards higher values of GUI in SLE patients than in the normal controls. The GUI values were also higher for SLE cases with a flare stage or a negative chest X-ray than in SLE cases with a stable stage or a positive chest X-ray. The statistical results reveal that the differences in the GUI values are not significant. However, we found that (1) positive chest X-ray findings may be a later manifestation of a lung inflammation and (2) the values of GUI parallel clinical features in SLE patients.     

Distribution of 67-Ga following intravenous administration: effects of disodium edetate therapy

Following intravenous administration of 67Ga-citrate to normal and abscessed rats, the colon content of 67Ga decreased with increasing oral doses of Na2EDTA. The effects observed, however, were not thought to be of potential clinical value.     

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.     

Excretion of endogenous and exogenous purine derivatives in sheep: effect of increased concentrate intake

The scintigraphic measurement of colonic transit is currently performed using 111In ion exchange resin pellets delivered to the colon in a capsule coated with a pH sensitive polymer, methacrylate, which dissolves in the distal ileum. However, in the USA, this requires an investigational drug permit. Our aim was to evaluate the in vitro binding characteristics of activated charcoal in milieus that mimicked gastric and small intestinal content. The in vitro incubation of activated charcoal was performed with Na99Tc(m)O4, 99Tc(m)-DTPA, 111InCl3, 111In-DTPA, 201TlCl and 67Ga-citrate in the pH range 2-4 and pH 7.2 at 37 degrees C. We estimated the association of radiopharmaceuticals with the activated charcoal over a 3 h in vitro incubation. With the exception of 67Ga-citrate, the association of activated charcoal with the other radiopharmaceuticals was approximately 100% throughout the 3 h incubation. In conclusion, activated charcoal appears to adsorb avidly with common radioisotopes, and appears promising as an alternative to resin ion exchange pellets used for the measurement of gastrointestinal transit by scintigraphy.     

Gallium imaging in pulmonary artery sarcoma mimicking pulmonary embolism: case report

Primary pulmonary artery sarcoma provides perfusion-ventilation images, as well as arteriographic studies, that can suggest pulmonary embolism. The awareness of atypical correlation among the studies for pulmonary embolism can lead to an early suspicion of pulmonary artery tumor. Imaging with 67Ga-citrate may facilitate earlier diagnosis.     

Uptake of 67Ga in the lactating breast and its persistence in milk: case report

The concentration of 67Ga in the milk of a postpartum woman was measured at intervals up to 8 days after the injection of 3 mCi of 67Ga-citrate. The 67Ga concentration was about 0.15 muCi/ml at 3 days after injection and fell to 0.035 muCi/ml by 8 days. Since the biologic clearance of gallium was slow (T1/2 approximately 9 days), the major determinant of the clearance of radioactivity was the physical decay of the gallium. An estimate of the radiation dose to a nursing infant suggests that nursing be interrupted for about 2 weeks after the mother has had a 67Ga study.     

Colonic transit time assessed by 67 Ga-citrate in a case-series of patients with recto-sigmoid adenomas

One plausible mechanism by which dietary factors may influence colorectal carcinogenesis is through their effect on intestinal transit time. This study examined colonic transit by means of oral 67Ga-citrate in a case-series of patients who had developed recto-sigmoid adenoma. Adenoma patients had a significantly shorter transit time than constipated patients (P = 0.01) and our results also suggest (but do not show conclusively) that colonic transit in adenoma patients is similar to that of normal controls. Although these findings require confirmation from a larger study, they raise the hypothesis that colonic transit times are not delayed in patients who harbour recto-sigmoid adenomas.     

Imaging experimental osteomyelitis using radiolabeled liposomes

We evaluated radiolabeled liposomes (liposomes labeled both with 99mTc and 111In) for the early detection of osteomyelitis in an experimental model. METHODS: Liposomes, containing 5% polyethylene glycol-distearoyl phosphatidylethanolamine with encapsulated glutathione and deferoxamine, were prepared and labeled with 99mTc and 111In by a previously described method. Acute osteomyelitis was induced in male New Zealand rabbits by intramedullary injection of sodium-morrhuate and Staphylococcus aureus in the tibial bone marrow. Serial imaging studies, consisting of radiolabeled liposome imaging (2-4 mCi 99mTc and 75-125 microCi 111In), 99mTc-methylene diphosphonate (MDP) (3-5 mCi) and 67Ga-citrate (500 microCi), were performed starting at the third day after injection. Each radionuclide study was separated by at least 2 days. The animals also underwent radiography of the lower extremities. The animals were then killed and the infected tibia was excised for histopathology. RESULTS: For interpreting relative efficacy of individual radiopharmaceuticals, only animals showing positive histopathological findings (n = 9) were considered. Radiographs (Days 12, 13) were conclusive for osteomyelitis in only 3 rabbits. Radiolabeled liposome imaging (Days 4-6) showed positivity in 8 cases and was equivocal in 1. Though the lesion could be delineated as early as 8 hr postinjection in the 99MTc window, the best target-to-nontarget ratio (T/NT) of 1.86 +/- 0.19 was obtained at 48 hr in the 111In window. Three-phase 99mTc-MDP scan (Day 7) was positive in only 5 rabbits with 3 hr T/NT of 1.6 +/- 0.23. Galium-67-citrate images (Days 9-11) were positive in 8 cases and equivocal in 1, the mean 48 hr T/NT being 1.74 +/- 0.24. These results show liposomes are better than 99mTc-MDP for imaging bone infection. Given the early localization and better quality of the images, radiolabeled liposomes also exhibited advantages over 67Ga-citrate for detection of acute osteomyelitis.     

Reverse dorsal digital and metacarpal flaps: a review of 27 cases

It was reported previously that normal soft tissues accumulate 67Ga by a transferrin-dependent route, but uptake by tumors can be transferrin independent. It was also reported that, although overexpression of the transferrin receptor can promote Ga avidity, the transferrin-independent uptake of 67Ga is significant and can be augmented to exceed transferrin-mediated levels by increasing extracellular calcium. In assessing the effect of calcium channel blockers on uptake of 67Ga, it was observed that, after exposure to light (either visible or ultraviolet [UV]), nifedipine strongly potentiates the cellular uptake of 67Ga by a transferrin-independent process. METHODS: The effect of nifedipine on 67Ga uptake as a function of time, concentration, duration and type of preexposure to light was determined in two cultured Chinese hamster ovary cell lines. One cell line lacks the transferrin receptor. In the other, the human transferrin receptor has been restored by transfection and is overexpressed constitutively. RESULTS: Although there are some differences in pattern of stimulation of uptake, nifedipine subjected to either UV or fluorescent light strongly promotes the uptake of 67Ga in the cultured cells in a time-dependent and concentration-dependent manner. Maximal uptake of 67Ga occurs when the cells are incubated for 30 min with 25 micromol/L nifedipine preexposed to either 4h of fluorescent or 1h of UV light. Under these conditions, uptake of 67Ga is 1000-fold greater than basal levels and 50-fold greater than can be achieved by the transferrin-dependent route. Light-shielded nifedipine has no effect on 67Ga uptake. CONCLUSION: The effect of photodegraded nifedipine on the uptake of 67Ga is independent of expression of the transferrin receptor. The potential for photodegraded nifedipine to improve oncologic imaging with 67Ga warrants further investigation.     

Distribution of gallium-67 in normal and hypotransferrinemic tumor-bearing mice

The mechanism by which 67Ga accumulates in tumors is controversial. The most popular theory is that 67Ga binds to transferrin and gains access to cells by the transferrin receptor. However, substantial evidence suggests that uptake of 67Ga may not be universally mediated by transferrin in tumors. To determine whether transferrin is required for uptake of 67Ga in vivo, we compared the uptake of 67Ga by two types of implanted tumors and by normal tissues in normal and severely hypotransferrinemic strains of Balb/C mice. One type of tumor was strongly gallium-avid in normal mice; the other was not. Uptake of 67Ga by normal soft tissues was markedly less in hypotransferrinemic than in normal mice. Uptake of 67Ga by bone was equivalent in the two types of mice. For the more gallium-avid tumor, uptake of 67Ga was similar and the ratio of tumor-to-background activity was substantially higher in the hypotransferrinemic than in the normal mice. For the less gallium-avid tumor, uptake was significantly less in hypotransferrinemic than in normal mice. These data suggest that uptake of 67Ga by bone and by some tumors may be a transferrin-independent process.     

Scintigraphy with gallium-67 citrate in patients with AIDS: pathologic extrapulmonary uptake

67Gallium citrate can accumulate in different inflammatory and neoplastic lesions. The mechanisms of 67Gallium uptake in abnormal tissue are still partially unknown and the tracer is considered a nonspecific indicator of disease. In AIDS patients, 67Gallium citrate is used in the diagnosis and characterization of opportunistic pulmonary infections and especially of Pneumocystis carinii pneumonia. From June 1989 through December 1992 in our Department 140 67Gallium scans were performed on 103 AIDS patients, referred for evaluation of pulmonary symptoms. All studies were carried out 72 hours after i.v. administration of 185 MBq 67Gallium citrate, with anterior and posterior views of head, chest and abdomen. The images were evaluated with conventional diagnostic criteria and site, number and intensity of abnormal foci of extrapulmonary uptake were recorded. Abnormal extrapulmonary uptake was found in 17 patients (12%): gastric (3, two of which also exhibited abnormal intestinal uptake), esophageal (1) hepatic (1), intestinal (2) renal (4), nodal (3), ocular (1), cutaneous (1), sinusal (1) localizations. In all cases clinical, endoscopic, bioptic or microbiological demonstration of the possible cause of 67Gallium uptake was obtained. An intriguing finding in our series was the lower incidence of gastric uptake (two patients with miliary tuberculosis and one patient with gastric candidiasis) than in the literature. This finding could be explained by clinical and epidemiologic differences between different patient populations. However, the scan interval after tracer administration should be also taken into account, since in our study scans were always performed at 72 hours, while in other series the interval ranged 24-48 hours. The relatively high incidence of abnormal extrapulmonary uptake confirms the opportunity of whole body exploration after 67Gallium administration in the patients with such multisystemic disease as AIDS, even when the patients are referred mainly for respiratory problems.     

Breast cyst simulating metastases on iodine-131 imaging in thyroid carcinoma

False-positive radioiodine uptake has been reported in many organ systems. We describe a female patient who had mixed papillary and follicular thyroid carcinoma, and on radioiodine total-body imaging demonstrated focal, lower-right chest uptake. Special prone imaging with the right breast dependent proved that the uptake was inside the right breast. Review of a recent breast ultrasound and mammograms showed this uptake to correspond to a large breast cyst. It is known that 131I breast uptake may be functional within the mammary gland. In this patient, it was due to retention within the cyst after the background activity decreased. Knowledge of this phenomenon may improve the interpretation of total-body 131INa studies.     

Effects of smoking cessation on insulin and cardiovascular risk factors--a controlled study of 4 months'' duration

MIB-1 Ki-67 and PCNA scores in infiltrating ductal NOS breast carcinomas were compared. The correlation between MIB-1, Ki-67 and PCNA indices and several clinicopathological factors that have prognostic significance in breast cancer was also assessed. The mean Ki-67, MIB-1 and PCNA indices were 13.4%, 19.4%, 27.6%, respectively. Significant positive linear correlation was found only between Ki-67 and MIB-1 indices. PCNA score did not correlate with Ki-67 and MIB-1 indices. The significant correlation between Ki-67 and MIB-1 scores and histological grade was found. There was no correlation between Ki-67 and MIB-1 indices and axillary lymph node status or tumor diameter. The results suggest that MIB-1 antibody is an excellent tool for assessment of proliferative rate of breast cancer cells in paraffin sections.     

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.     

Estimation of the proliferative activity of human breast cancer tissue by means of the Ki-67 and MIB-1 antibodies--comparative studies on frozen and paraffin sections

The estimation of the Ki-67 index in human breast cancer tissue has been proven to be a useful prognostic tool. The examination can be performed, however, only on frozen sections (FS). The development of an antibody directed against parts of the Ki-67 antigen (MIB-1) has opened a new route to determine the proliferative activity on paraffin sections (PS). MIB-1 immunohistochemistry is used instead of Ki-67 immunohistochemistry if a tumour is delivered to the pathologist after formalin fixation or if that part of the tissue suspicious for breast cancer must be totally embedded in order to confirm the diagnosis. The present study compares the findings of Ki-67 (FS) and MIB-1 (FS and PS) immunohistochemistry in a total of 544 cases of human breast cancer. The findings confirm a good statistical correlation between the Ki-67 and the MIB-1 findings. The MIB-1 results are 2-2.5 times higher in FS than in PS. Good agreement exists between the Ki-67 indices determined on FS and the MIB-1 indices determined on PS. If the cut-off value for the separation of Ki-67 negative and positive cases is defined as 10%-20%, a MIB-1 index in PS of 10% permits the correct prediction of a negative Ki-67 index in 97% of the cases, and a MIB-1 index of 30% or more correctly predicts a positive Ki-67 index in 90% or more of the cases. Hence, the determination of the MIB-1 index on PS may replace the determination of the Ki-67 index on FS with a high degree of probability.     

Clinical value of scintigraphic tumor diagnosis by means of test substances with tumor affinity. 2. Gallium radioisotopes

Deriving from the principle of direct tumor visualization and the beginnings of positive imaging of malignant tumors, radiotracers with tumor affinity are distinguished by those with tumor-specific and non-specific uptake. With special regard to the tumor-specific localization of thyroid carcinomas using radioiodine (131J) and of osteoplastic bone tumors or metastases using 99m-labelled phosphate compounds, the tumor scintigraphy results mainly with radiopharmaceuticals possessing tumors affinity, however not a tumor-specific uptake. On the basis of experimental and clinical results Gallium-67, one of these tumor-seeking agents, has become most important tumor scintigraphy. The diagnostic possibilities and limitations in using Gallium-67 for tumor imaging are derived from: 1) the non-specific uptake of Gallium-67, 2) the diagnosis accuracy and its reasons, and 3) the determinant factor of viability of tumor affecting the Gallium-67 accummulation.     

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.     

Conjugation of the monoclonal antibody 17-1A with the nitroacridine compound C921 with the poly-L-lysine as an intermediate agent

Transferrin and transferrin receptors play an important role in the transport of iron into the brain. To determine whether gallium enters the brain by the same mechanism, uptakes of 67Ga and 59Fe have been compared under controlled conditions. Rates of gallium penetration into brain (K(in)) were four times slower than those for 59Fe. K(in) for 67Ga when infused with citrate were 0.88 +/- 0.24 and 0.94 +/- 0.39 x 10(-3) ml g-1h-1 for cerebral hemisphere and cerebellum, respectively. When infused as the transferrin complex, 67Ga uptake into the brain was not different from that when infused with citrate. The presence of the anti-transferrin receptor antibody OX-26 significantly reduced uptake of 59Fe by 60% and 64% into cerebral hemisphere and cerebellum, respectively. By contrast, pretreatment of rats with OX-26 enhanced the uptake of 67Ga into brain, particularly when infused with citrate; mean increases in uptake of 67Ga were 120% and 144% for cerebral hemisphere and cerebellum, respectively. Purified 67Ga-transferrin was also taken up into both brain regions examined in the presence of OX-26. These results indicate that the transport of non-transferrin bound gallium is an important mechanism for gallium uptake into brain.