Tumor uptake of 67Ga-carrying liposomes

The in vivo distribution, excretion, and tumor localization of liposome-encapsulated ⁶⁷Ga in normal and Ehrlich tumor (solid form)-bearing mice were studied. In normal mice, multilamellar vesicles (MLVs) were taken up mainly by the liver and spleen, whereas small unilamellar vesicles (SUVs) exhibited a broader tissue distribution. When ⁶⁷Ga was encapsulated in MLVs or SUVs, the excretion of the radiotracer in the urine and feces was less than that observed for free tracer at 72 h after i.v. administration. In tumor-bearing mice, SUVs were found to accumulate preferentially in tumors. The tumor uptake of neutral, positive, and negative SUVs was 10%–13% of the administered dose per gram of tumor tissue at 24 h after their injection. These values were about three times higher than those found for free ⁶⁷Ga-nitrilotriacetic acid (⁶⁷Ga-NTA) or ⁶⁷Ga-citrate. Significant differences in tumor uptake due to different surface charges of liposomes were not observed. Enhanced tumor-to-blood and tumor-to-muscle ratios were also observed at 24 h after injection. These results suggest that ⁶⁷Ga-carrying liposomes may be a useful for tumor imaging.     

Tumor and liver uptake models of 67Ga-citrate

After administration ⁶⁷Ga concentrates with time in lysosomes from the cytoplasm of liver cells. The lysosomal role in the accumulation of ⁶⁷Ga in the liver cell is weakened upon transformation of the liver cell into a malignant tumor cell. In malignant tumors (except for hepatoma) the lysosome does not play a major role in the tumor concentration of ⁶⁷Ga. ⁶⁷Ga is bound to acid mucopolysaccharides (keratan polysulfate, etc.) in both tumor and liver. In liver cells, large amounts of ⁶⁷Ga are transported into lysosomes with these acid mucopolysaccharides, and in hepatoma cells, quite large amounts of ⁶⁷Ga are transported into lysosomes with these acid mucopolysaccharides. In malignant tumor cells (except for hepatoma) the effect is much smaller, the acid mucopolysaccharides transporting very little ⁶⁷Ga into lysosome.The ⁶⁷Ga is concentrated in viable tumor tissue within malignant tissue but hardly at all in necrotic tumor tissue, and concentrates avidly in inflammatory infiltration around tumor cells. Plenty of ⁶⁷Ga is found in liver but very little in connective tissue associated with the liver.     

Tumor and liver uptake models of 67Ga-citrate

After administration 67Ga concentrates with time in lysosomes from the cytoplasm of liver cells. The lysosomal role in the accumulation of 67Ga in the liver cell is weakened upon transformation of the liver cell into a malignant tumor cell. In malignant tumors (except for hepatoma) the lysosome does not play a major role in the tumor concentration of 67Ga. 67Ga is bound to acid mucopolysaccharides (keratan polysulfate, etc.) in both tumor and liver. In liver cells, large amounts of 67Ga are transported into lysosomes with these acid mucopolysaccharides, and in hepatoma cells, quite large amounts of 67Ga are transported into lysosomes with these acid mucopolysaccharides. In malignant tumor cells (except for hepatoma) the effect is much smaller, the acid mucopolysaccharides transporting very little 67Ga into lysosome. The 67Ga is concentrated in viable tumor tissue within malignant tissue but hardly at all in necrotic tumor tissue, and concentrates avidly in inflammatory infiltration around tumor cells. Plenty of 67Ga is found in liver but very little in connective tissue associated with the liver.     

Ga-67 cardiac uptake

A case of positive Ga-67 image due to tuberculous pericarditis is presented. The pattern and distribution of the uptake suggested that the concentration of the activity was mainly in the inflamed pericardium. The known causes of Ga-67 cardiac uptake were reviewed, and a differential diagnosis is given.     

Gastric gallium-67 uptake in gastritis

Even though Ga-67 imaging has been used widely in the diagnosis of malignant as well as inflammatory lesions, its uptake in the stomach has been reported in the literature mainly in gastric lymphoma and carcinoma. As shown in this case, intense gastric uptake of the radionuclide may be seen in common gastritis without malignancy. Perhaps the benign gastric uptake of Ga-67 deserves more emphasis.     

Gallium-67 uptake in non-malignant stomach

Although ⁶⁷Ga imaging has been widely used in the diagnosis of malignant and inflammatory diseases, its uptake in the stomach has been reported in the literature mainly in gastric lymphoma and carcinoma. As shown by this report, intense gastric uptake of the radionuclide may be seen not only in malignancy, but also in gastritis, and even in the stomach without known disease. Perhaps, the benign gastric uptake of ⁶⁷Ga deserves more emphasis in the literature. Our findings would suggest that gastroscopy and biopsy are not necessarily indicated solely because of the gastric concentration of ⁶⁷Ga.     

Gallium-67 uptake in cutaneous sarcoidosis

A case of abnormally increased gallium-67 uptake by cutaneous lesions in sarcoidosis is reported. The patient also had active sarcoidosis in lungs, periaortic lymph glands, salivary, and lachrymal glands     

Gallium-67 uptake in meningeal sarcoidosis

A case of sarcoidosis limited to the central nervous system is described in which the diagnosis was suggested by high Ga-67 uptake in the cranial and spinal meninges. The diagnosis was confirmed by meningeal biopsy. Treatment with oral corticosteroids resulted in clinical improvement and marked reduction in Ga-67 uptake in the meninges. This is the first reported case of the central nervous system sarcoid diagnosed by Ga-67 imaging.     

Increased delivery of gallium-67 to tumors using serum-stable liposomes

Gallium-67 chelated to nitrilotriacetic acid was encapsulated in liposomes composed of various phospholipids, and 67Ga delivery potential to the tumor after intravenous injection of these liposomes was examined. Tumor uptake of the liposomes themselves and their stability in the serum were also studied. It was found that liposomes composed of distearoylphosphatidylcholine, diarachidoylphosphatidylcholine, or sphingomyelin with cholesterol (molar ratio of phospholipid:cholesterol, 2:1) could be taken by the tumor effectively and could deliver large amounts of 67Ga to the tumor. They could also give high 67Ga accumulation ratios (tumor to the other tissues). The study of liposomal stability in the serum suggested that the marked 67Ga accumulation in the tumor resulted from the serum stability of the liposomal bilayer, i.e., the stable liposomes in the blood circulation could reach the tumor in large quantities after i.v. injection. These observations indicate that liposomes with an appropriate lipid composition may be an excellent tool to accumulate 67Ga in tumors.     

Diffuse gallium-67 uptake in radiation pneumonitis

To evaluate the clinical usefulness of Ga-67 imaging for the assessment of radiation pneumonitis, 12 patients who had developed radiation pneumonitis after receiving radiotherapy alone for non-small-cell lung cancer from 1979 through 1988 were reviewed. Diffuse bilateral Ga-67 uptake occurred in 5 out of the 12 cases; in the other 7 cases, Ga-67 uptake was confined to the irradiation lung. Conversely, chest radiography showed infiltrates only in the irradiated lung. Histopathology of the lung in four out of the five cases that showed diffuse Ga-67 uptake in the lung, however, revealed that the lung outside the radiation field with Ga-67 uptake was consistent with interstitial pneumonitis induced by radiation. These results suggest that radiation pneumonitis could extend beyond the irradiated lung and that Ga-67 imaging is more useful than chest radiography for the assessment of the spatial extent of radiography pneumonitis.     

Gallium-67 renal uptake in Sjogren's syndrome

This case report describes a 61-year-old male with Sjogren's syndrome. Diffuse Ga-67 uptake in the kidneys was seen due to renal involvement with this disorder. Sjogren's syndrome should be considered in the differential diagnosis of diffuse bilateral Ga-67 accumulation in the kidneys.     

Gallium-67 pulmonary uptake in eosinophilic pneumonia

Eosinophilic pneumonia is usually diagnosed based on the findings on chest x-ray, white blood count, and transbronchial biopsy. After reporting a case of Ga-67 lung uptake in eosinophilic pneumonia, its histopathology is discussed and the mechanisms of Ga-67 uptake by inflammatory lesions are reviewed.