Biodistributions of 201Tl in tumor bearing animals and inflammatory lesion induced animals

The accumulation of ²⁰¹Tl in tumor and inflammatory tissues were small. However, this nuclide showed a high concentration in viable tumor tissue, less in connective tissue (containing inflammatory tissues), and was not seen in necrotic tumor tissue regardless of the time after administration of ²⁰¹Tl(I)-chloride. In inflammatory lesions, ²⁰¹Tl accumulated in subcutaneous tissue infiltrated with neutrophils and macrophages, and quite large amounts of this nuclide were accumulated in subcutaneous tissue and sites where neutrophils were croeded. Most ²⁰¹Tl existed in a free form in the fluid of tumor and inflammatory tissues regardless of the time after administration. A small amount of this nuclide was localized in the nuclear, mitochondrial and microsomal fractions in these tissues, and the nuclide was bound to protein in these fractions. The distribution of ²⁰¹Tl(III)-chloride in tumor bearing animals was essentially the same as that of ²⁰¹Tl(I)-chloride.     

Biodistributions of radioactive alkaline metals in tumor bearing animals: comparison with 201Tl

The retention values for 42K, 86Rb and 134Cs in the tissues and blood were quite similar to those for 201Tl, but were very different from those for 22Na. In an experiment for subcellular fractionation of tumors, most of these nuclides were localized in the supernatant fraction, with small amounts in other fractions. The concentration ratios for these nuclides in each fraction were approximately constant regardless of the time after administration. Radioactive alkaline metals in the supernatant fraction of the tumor homogenate existed mostly as free ions and were bound to protein in other fractions of tumor tissue. These results were essentially the same as those for 201Tl. Ouabain suppression studies indicated that 201Tl is taken up into the tumor cells partly through Na+, K+-ATPase of their membranes. Ionic radii of alkaline metals and thallium were related to their blood and tumor retention values. This relationship suggested that monovalent cations whose ionic radii exceed 0.133 nm, and which exist as free ions in the tissue fluids, behave like the potassium ion. Potassium and K analogs (Tl, Rb, Cs) are avidly taken up into viable tumor cells whose Na+, K+-ATPase activity is elevated. Therefore, suitable radionuclides of K and K analogs can be excellent agents for visualization of viable tumor tissues.     

Biodistributions of radioactive alkaline metals in tumor bearing animals: comparison with 201Tl

The retention values for ⁴²K, ⁸⁶Rb and ¹³⁴Cs in the tissues and blood were quite similar to those for ²⁰¹Tl, but were very different from those for ²²Na. In an experiment for subcellular fractionation of tumors, most of these nuclides were localized in the supernatant fraction, with small amounts in other fractions. The concentration ratios for these nuclides in each fraction were approximately constant regardless of the time after administration. Radioactive alkaline metals in the supernatant fraction of the tumor homogenate existed mostly as free ions and were bound to protein in other fractions of tumor tissue. These results were essentially the same as those for ²⁰¹Tl. Ouabain suppression studies indicated that ²⁰¹Tl is taken up into the tumor cells partly through Na⁺, K⁺-ATPase of their membranes. Ionic radii of alkaline metals and thallium were related to their blood and tumor retention values. This relationship suggested that monovalent cations whose ionic radii exceed 0.133 nm, and which exist as free ions in the tissue fluids, behave like the potassium ion. Potassium and K analogs (Tl, Rb, Cs) are avidly taken up into viable tumor cells whose Na⁺, K⁺-ATPase activity is elevated. Therefore, suitable radionuclides of K and K analogs can be excellent agents for visualization of viable tumor tissues.     

Experimental study on tumor affinity of 201Tl-chloride

The tumor affinity of ²⁰¹Tl was studied with normal and VX-2 cancer-bearing rabbits. ²⁰¹Tl distribution in normal rabbit tissues was greatest in the kidney and heart muscle, followed by thyroid gland small intestine, spleen, lung, liver, bone marrow, bone, skeletal muscle, and blood, respectively. Accumulation into the thyroid varied greatly according to individuals. Generally, the taller the height of follicular cells, the greater was the affinity.Accumulation of ²⁰¹Tl into the tumor transplanted into femoral muscle reached its maximum within 1 h after administration, and thereafter decreased gradually.When the tumor affinity was compared with that of ⁶⁷Ga, the ratio of ⁶⁷Ga accumulation to tissues (except blood) was greater than that of ²⁰¹Tl.Accumulation of ²⁰¹Tl is significantly correlated to that of ⁴²K, and the mechanism of ²⁰¹Tl-tumor affinity seems to be triggered by the acceleration of the potassium metabolism of a tumor. Accumulation into the inflammatory focus was greater with ⁶⁷Ga as a ratio to muscle, while the ratio to blood was greater with ²⁰¹Tl.     

New color imaging of [99mTc]-pyrophosphate and [201Tl]-chloride dual isotope single photon emission computed tomography in acute myocarditis

[99mTc]-pyrophosphate (PYP) and [201Tl]-chloride dual isotope single photon emission computed tomography (SPECT) is now available to detect the site and extent of acute myocardial infarction. In inflammatory myocardial disease, [99mTc]PYP makes hot image on damaged area. We performed dual isotope SPECT of [99mTc]PYP and [201Tl]Cl in two patients with acute myocarditis and severe rhythm disturbance to evaluate the severity of inflammation. Myocardial damage was estimated by [201Tl] perfusion coloring blue and myocardial inflammation was estimated by [99mTc]PYP uptake coloring red. The overlap display of both images made it clear to detect spatial extent of myocardial inflammation. Using this technique, we expect to estimate the severity of myocarditis and to make a decision of therapeutic plan.     

Uptake of99mTc-tetrofosmin,99mTc-MIBI and201TI in malignant thymoma

99mTc-tetrofosmin, Thallium-201-chloride (201Tl) and 99mTc-MIBI imagings were performed in a patient with malignant thymoma. Tracer uptake in the primary tumor was demonstrated. The tumor-to-background ratios of planar and SPECT imagings were 1.60 and 1.98 for 99mTc-tetrofosmin, 1.12 and 2.09 for 201Tl, and 1.19 and 1.80 for 99mTc-MIBI, respectively. In another patient 99mTc-tetrofosmin and 201Tl imagings were performed. Not only the primary tumor but also the direct invasions and metastatic lesions (bone metastases) were clearly detected. The tumor-to-background ratios of planar and SPECT imagings were 2.31 and 2.78 for 99mTc-tetrofosmin and 2.45 and 3.58 for 201Tl, respectively. In 99mTc-tetrofosmin scintigraphy we acquired delayed images, and the tumor-to-background ratios of planar and SPECT delayed images were 1.20 and 1.86, the retention ratios were -1.11 and -0.92 and the retention indices were -48.1 and -33.1, respectively. Our preliminary results suggest that 99mTc-tetrofosmin is useful in detecting not only the primary tumor but also metastatic lesions from malignant thymoma.     

Affinity of 167Tm-citrate for tumor and liver tissue

Strong affinity of 167Tm-citrate for tumor tissue was reconfirmed by using Ehrlich tumor. Excellent tumor imaging was obtained with 167Tm-citrate because of its strong tumor affinity and because of the suitable physical characteristics of 167Tm. A large number of 167Tm had accumulated in the connective tissue which contained inflammatory tissue, quite large amounts were found in areas containing viable and necrotic tumor tissue, and small amounts were present in viable tumor tissue. 167Tm was not seen in necrotic tumor tissue. It was concluded that lysosomes did not play a major role in the tumor concentration of 167Tm, but played an important role in the liver concentration of this nuclide. In the case of hepatoma AH109A, it was presumed that lysosomes played a considerably important role in the tumor concentration of 167Tm, hepatoma AH109A possessing some residual features of the liver. 167Tm was bound to acid mucopolysaccharides and transposed by the acid mucopolysaccharides in the tumor tissues and liver. The acid mucopolysaccharides to which 167Tm were bound in tumor and liver, were heparan sulfate, chondroitin sulfate (or keratosulfate) and heparin (or keratosulfate).     

Relationship between the biodistributions of radioactive metal nuclides in tumor tissue and the physicochemical properties of these metal ions

This study was undertaken to elucidate the relationship between the biodistribution of radioactive metal nuclides in tumor tissue and its physicochemical properties. Potassium analogs (86Rb, 134Cs, 201Tl) were taken up into viable tumor tissue, although 22Na concentrated in necrotic tumor tissue. 67Ga and 111In were more predominant in inflammatory tissue than in the viable and necrotic tumor tissue. 169Yb and 167Tm accumulated in viable tumor tissue and tissue containing viable and necrotic tumor tissue. 67Ga, 111In, 169Yb and 167Tm were bound to the acid mucopolysaccharide with a mol. wt. of about 10,000 daltons in the tumor tissue. 46Sc, 51Cr, 95Zr, 181Hf, 95Nb, 182Ta, and 103Ru were highly concentrated in inflammatory tissue and were bound to the acid mucopolysaccharides with a mol. wt. exceeding 40,000 daltons. 65Zn and 103Pd concentrated in viable tumor tissue and were bound to the protein in the tissue. The results suggest that the difference in intra-tumor distribution of these elements is caused by a difference in the binding substances (or status) of these elements in the tissues, and the binding substance is determined by physicochemical properties of the elements. We therefore conclude that the biodistribution of radioactive metal ions in tumor tissue is determined by its own physicochemical properties.     

67Ga accumulation in inflammatory lesion and its mechanism: comparison with malignant tumor

The accumulation of 67Ga in inflammatory lesions increased with time after injection of turpentine oil and reached a plateau 5 days later. At that time the uptake in the lesions was larger than any other tissue, after ten days the lesion uptake decreased. In experiments using rats which had been kept for 5 days after subcutaneous injection of turpentine oil, the accumulation of 67Ga in inflammatory lesions increased with time until six days after administration of 67Ga-citrate. It is clear from this study that 67Ga is avidly accumulated in areas where the subcutaneous tissue is infiltrated with neutrophils and macrophages, that it is not accumulated at the sites in which neutrophils are crowded, that nuclear material, mitochondria, lysosomes and microsomes do not play a major role in 67Ga accumulation in the lesion and that the main binding acid mucopolysaccharide in the lesion is a acid mucopolysaccharide which is none of the following: keratan sulfate, heparan sulfate, heparin, or chondroitin sulfate A, B or C. It is presumed that the main 67Ga binding acid mucopolysaccharide is keratan polysulfate (or other oversulfated acid mucopolysaccharides).     

Relationship between cancer cell proliferation and thallium-201 uptake in lung cancer

Although thallium-201 (201Tl) uptake is related to perfusion in many normal tissues, the biologic rationale for 201Tl uptake in tumors is uncertain. To determine if tumor uptake is related to cell proliferation, we correlated the relative retention of 201Tl in lung tumors with expression of Ki-67, an indicator of cell proliferation. METHODS: Sixty patients with lung tumors, included small cell carcinoma (n = 8) and non-small cell carcinoma (n = 52), underwent 201Tl single photon emission computed tomography (SPECT) imaging. The 201Tl lesion uptake was determined on early and delayed images and the radiotracer retention index (RI) was calculated. Tumor specimens were obtained at surgery or bronchoscopy. The cell proliferation ratio was estimated with MIB-1, a monoclonal antibody that recognized the nuclear antigen Ki-67. RESULTS: The average 201Tl index was 2.13+/-0.61 (early) and 2.46+/-0.83 (delayed). The average RI was 17.44+/-35.01. Overall, the 201Tl index (delayed) and the cancer cell proliferation were correlated (r = 0.70, p < 0.0001). Of interest, there was a significant correlation (r = 0.872, p < 0.0005) between the 201Tl index on delayed images and the cell proliferation ratio in patients with small cell but not non-small cell lung carcinoma. The 201Tl index (delayed) was significantly higher (p < 0.0001) in patients with small cell lung carcinoma than in patients with non-small cell lung carcinoma. CONCLUSION: 201Tl imaging appears to be useful for evaluating patients with small cell lung carcinoma but not non-small lung carcinoma, and is correlated with the monoclonal antibody MIB-1, a marker of cell proliferation.     

Comparison of 99mTc-methoxyisobutyl isonitrile and 201Tl scintigraphy for detection of residual thyroid cancer after 131I ablative therapy.

In this study, we compared 99mTc-methoxyisobutyl isonitrile (MIBI) with 201Tl scintigraphy for the detection of residual thyroid cancer not found by 131I scans in patients with increased risk of recurrence after 131I therapy. METHODS: 201Tl and MIBI scans were obtained in 54 patients with negative 131I scans 3-25 y (median 7.9 y) after the first postsurgical 131I therapy. Serum thyroglobulin (Tg) levels were measured while patients were receiving thyroid hormone and again 6 wk after withdrawal of hormone therapy. RESULTS: The overall results were the same for both 201Tl and MIBI imaging, with a sensitivity of 19 of 36 (53%), specificity of 17 of 17 (100%) and accuracy of 36 of 54 (69%). Planar images missed residual cancer in high cervical lymph nodes adjacent to salivary gland activity, in small nodes (<1 cm) deep in the neck or chest and with diffuse pulmonary micrometastases. Serum Tg was elevated in 24 of 36 (67%) patients with residual cancer; 201Tl detected tumor sites in 13 of 24 (54%) of these patients, and MIBI detected tumor sites in 14 of 24 (58%) of these patients. Of the 12 patients who had residual cancer and false-negative serum Tg levels, 6 had true-positive 201Tl and 5 had true-positive MIBI scans. CONCLUSION: 201Tl and MIBI planar imaging yield the same high specificity and positive predictive value for residual thyroid cancer in patients with high-risk profiles and negative radioiodide scans. Both imaging agents detected residual cancer in more than half of the patients in whom conventional staging techniques did not reliably detect either the presence or the extent of residual thyroid cancer and changed the management in patients with surgically resectable cancer.     

Evaluation of 201Tl SPECT in patients with glioma: a comparative study with histological diagnosis, clinical feature and proliferative activity]

The purpose of this study is to clarify the usefulness of 201Tl brain SPECT in the prediction of clinical degree of malignancy. Quantitative evaluation of 201Tl uptake in the tumor was expressed as count ratio of tumor site over contralateral normal region (D/C ratio) on 201Tl SPECT image. Fourteen patients with gliomas received an intravenous administration of bromodeoxyuridine (BUdR) at surgery to label tumor cells in the DNA synthesis phase. BUdR-positive cells in excised tumor specimen were stained with anti-BUdR monoclonal antibody by indirect immunoperoxidase staining. Percentage of labeled cells in relation to the total number of tumor cells in microscopic fields was defined as labeling index (BUdR-LI). D/C ratio in patients with grade IV glioma (198.7 +/- 31.7) was higher than that in patients with grade III glioma (138.3 +/- 33.9) or more low-grade gliomas (94.2 +/- 11.9, p less than 0.001). BUdR-LI in patients with high-grade glioma was also higher than that in patients with low-grade glioma. D/C ratio correlated well (r = 0.753) with BUdR-LI, which is considered to represent proliferative activity of the tumor. D/C ratio does not only correlate well with histological grade of glioma, but with clinical course or prognosis of individual patient with glioma. In conclusion, degree of 201Tl uptake in the tumor may provide non-invasive prediction of malignancy grade of gliomas and accurate estimation of efficacy of the therapy and early detection of recurrence or malignant transformation of the tumors, by delineating viable tumor tissue in patients with gliomas.     

Axonal transport of rubidium and thallium in the olfactory nerve of mice

Following intranasal administration of radioactive (86)Rb(+) and (201)Tl(+) in mice, we observed this direct transport via the olfactory nerve pathway. The (86)RbCl and (201)TlCl solutions were administered to two groups of mice, the unilateral intranasal and intravenous administration groups. After sacrifice, their heads were divided into the right and left side, which were then subdivided into seven parts; the nasal mucosa and brain regions were separated. Following the unilateral intranasal administration, uptake after 6 h by the olfactory bulb was significantly higher on the ipsilateral side ((86)Rb, 0.7 %dose; (201)Tl, 0.5 %dose) than on the contralateral side ((86)Rb, 0.08 %dose; (201)Tl, 0.15 %dose). Moreover, the (86)Rb and (201)Tl that accumulated in the olfactory bulb were gradually transported to other brain regions of the olfactory tract, the telencephalon and the diencephalon on the side corresponding to the nostril used for administration. Significant differences were observed between the right and left side of the brain regions 6 and 12 h after administration. Further, (201)Tl autoradiography clearly showed striped patterns of dense accumulation, localized in the region around the glomerular layer and granule cell layer of the olfactory bulb and around the olfactory cortex. These results provide clear evidence of axonal transport via the olfactory nerve pathway, from nasal cavity to the olfactory bulb, as well as to the olfactory cortex through the synaptic junctions. The olfactory transport of the (86)Rb(+) and (201)Tl(+) is thought to represent the behavior of K(+) in the olfactory system.     

Thallium-201 brain tumor imaging: a comparative study with pathologic correlation

In patients with gliomas who were stable or improving, we noted a disparity between clinical status and computed tomography (CT) brain scan results. To elucidate this finding, 29 patients were sequentially scanned with 2.0 mCi of 201Tl (5-30 min), 20 mCi [99mTc]gluceptate (GH) (3-4 hr) and 7-10 mCi 67Ga (48-72 hr). A total of 198 images were obtained. A set of three scans at a midpoint in follow up was selected for analysis. Seven patients who died had neuropathologic data available; brain sections were reconstructed to match radionuclide views without knowledge of image results. In the seven patients with autopsy data, 201Tl offered the most accurate correlation with viable tumor. Gallium-67 gave similar results in patients not receiving steroids. Technetium-99m GH scans could not allow differentiation between tumor, necrosis, and edema. Similarly, the CT scan could not routinely differentiate between fibrotic, nonfibrotic, necrotic, and neoplastic tissue. In the 22 patients without autopsy data, 201Tl scans commonly showed smaller and more focal abnormal uptake when compared with [99mTc]GH and 67Ga scans. Thallium-201 scans more accurately reflect viable tumor burden than other radionuclide studies of primary brain tumors, are minimally affected by concomitant steroid administration, can be performed immediately following tracer administration, and complement the anatomic data obtained from CT scans.     

Relationship between thallium-201 uptake by supratentorial glioblastomas and their morphological characteristics on magnetic resonance imaging

Single-photon emission tomography (SPET) with thallium-201 is used in the assessment of patients with gliomas because the amount of²⁰¹Tl accumulated by the tumoral cells increases in proportion to the degree of tumour malignancy, thus making it possible to differentiate high-grade from low-grade gliomas or recurrences from radiation necrosis. However, in large areas of tissue such as those examined in²⁰¹Tl SPET studies, the uptake of²⁰¹Tl may vary considerably even in tumours with the same histological diagnosis, as occurs in glioblastomas (GBMs). In order to evaluate the possible influence of the macroscopic characteristics of tumours on²⁰¹Tl uptake, we studied a series of 13 patients with histologically proven GBMs, comparing magnetic resonance imaging (MRI) parameters such as tumour dimensions, perilesional oedema, intratumoral necrosis and contrast enhancement with the degree of²⁰¹Tl uptake. The patients underwent both²⁰¹Tl SPET and MRI before surgery. The²⁰¹Tl index (tumour/contralateral unaffected brain) was calculated using two different region of interest (ROI) methods: the first employed irregular large ROIs (3.2±13.9 cm²) including pixels with more than 50% maximum activity; the second employed regular square small ROls (2.7 cm²) centered on the maximum activity of the lesion. Of the MRI morphological parameters studied, only necrosis significantly reduced the degree of²⁰¹Tl uptake in GBMs when larger ROIs were used. However, by using small regular ROIs the influence of necrosis on²⁰¹Tl uptake was found to be less relevant. Since necrosis is related to tumour proliferative activity and represents a negative prognostic factor in astrocytoma, a possible underestimation of²⁰¹Tl uptake due to intratumoral necrosis must be carefully evaluated.     

Thallium-201 SPECT imaging of brain tumors: methods and results

Recent studies suggest that thallium-201 (201Tl) planar scans of brain tumors more accurately reflect viable tumor burden than CT, MRI, or radionuclide studies with other single-photon emitting compounds. We have previously reported the utility of 201Tl SPECT index in distinguishing low- from high-grade gliomas elsewhere. Here we describe the technical considerations of deriving a simple 201Tl index, based on uptake in the tumor normalized to homologous contralateral tissue, from SPECT images of brain tumors. We evaluated the importance of consistently correcting for tissue attenuation, as it may achieve better lesion discrimination on qualitative inspection, and the methodologic limitations imposed by partial volume effects at the limits of resolution.     

A comparative study of<Superscript>2O1</Superscript>T1 scintigraphy and three-phase bone scintigraphy following therapy in patients with bone and soft-tissue tumors

OBJECTIVE: The purpose of this study was to evaluate the usefulness of 201Tl scintigraphy in comparison with three-phase bone scintigraphy in the differentiation of residual/recurrent tumors from post-therapeutic changes, in patients previously treated for bone and soft-tissue tumors. METHODS: Thirty-five 201Tl and three-phase bone scintigraphy scans were obtained for 30 patients with a history of bone or soft-tissue tumor who had undergone chemotherapy, radiation therapy, tumor resection, or a combination of these treatments. The planar 201Tl images were acquired 10 mins (early) and 2 hrs (delayed) after the intravenous injection of 111 MBq 201Tl-chloride. Three-phase bone scintigraphy was performed using 740 MBq 99mTc-HMDP at the same lesion site as for 201Tl imaging. The blood flow images were obtained every 10 sec for 2 mins and were immediately followed by the blood pool image after 5 mins. Three to 4 hrs later, bone images were obtained. 201Tl and three-phase bone scintigraphies were correlated with the histopathologic findings and/or clinical follow-up of more than 3 months. RESULTS: Of the 35 cases, 15 were free of disease and 20 had residual or recurrent tumors. Of the 20 residual or recurrent cases, all had true-positive 201Tl early and delayed scans, while bone scintigraphy was true-positive on the blood flow, blood pool and bone images in 16, 18 and 12 cases, respectively. 201Tl early and delayed images and 99mTc-HMDP blood flow and blood pool images were false-positive in one patient. The histology of this false-positive case showed the presence of lymph proliferative tissue. CONCLUSIONS: Although 201Tl uptake after treatment does not always indicate recurrence, 201Tl scintigraphy may still be more useful than three-phase bone scintigraphy in the follow-up of patients with bone and soft-tissue tumors following therapy.     

Gliosarcoma with thallium-201 SPECT

Thallium-201 (201Tl) chloride scintigraphy is the imaging method use for the detection of various tumors including glioblastoma, but only limited information on 201Tl uptake in gliosarcoma is available. We investigated a patient with gliosarcoma by means of 201Tl single-photon emission computed tomography (SPECT) and MRI. SPECT imaging revealed high 201Tl uptake in the tumor, which was closely correlated with contrast-enhancement on MRI. These results suggest that SPECT with 201Tl may be useful for detecting gliosarcoma and provide physiological information on this tumor.     

Determination of medullary thyroid carcinoma metastases by 201Tl, 99Tcm(V)DMSA, 99Tcm-MIBI and 99Tcm-tetrofosmin.

Medullary carcinoma of the thyroid (MCT) is malignancy derived from the parafollicular cells (or C-cells) of the thyroid. It is usually sporadic, although it is familial in some cases. Several scintigraphic procedures can provide information regarding the primary and metastatic foci of the tumour. We performed whole-body scanning to establish the pathology of MCT using 201Tl, 99Tcm(V)DMSA and 99Tcm-MIBI in 14 patients, and found average sensitivities of 73%, 82% and 81%, respectively. Moreover, we also scanned three patients with 99Tcm-tetrofosmin and identified two of four pathological foci as well as residual thyroid tissue. The sensitivities of 201Tl, 99Tcm(V)DMSA and 99Tcm-MIBI were 100%, 100% and 85% in identifying lymphadenopathies; 40%, 50% and 71% for soft tissue foci; 100% and 100% for foci in pulmonary parenchyma; and 100%, 66% and 100% for recurrences in thyroid gland. Although 99Tcm(V)DMSA identified all bony metastases in three patients (100%), 99Tcm-MIBI detected only two of three foci (66%) and 201Tl none. 201Tl, 99Tcm-MIBI and 99Tcm-tetrofosmin accumulated in residual thyroid tissue, but 99Tcm(V)DMSA did not, as expected. We conclude that these agents were complementary, since they had different sensitivities in different tissues. The tumour-seeking properties of tetrofosmin are to be evaluated in a larger series.     

67Ga accumulation in inflammatory lesion and its mechanism: Comparison with malignant tumor

The accumulation of ⁶⁷Ga in inflammatory lesions increased with time after injection of turpentine iol and reached a plateau 5 days later. At that time the uptake in the lesions was larger than any other tissue, after ten days the lesion uptake decreased. In experiments using rats which had been kept for 5 days after subcutaneous injection of turpentine oil, the accumulation of ⁶⁷Ga in inflammatory lesions increased with time until six days after administration of ⁶⁷Ga-citrate. It is clear from this study that ⁶⁷Ga is avidly accumulated in areas where the subcutanous tissue is infiltrated with neutrophils and macrophages, that it is not accumulated at the sites in which neutrophils are crowded, that nuclear material, mitochondria, lysosomes and microsomes do not play a major role in ⁶⁷Ga accumulation in the lesion and that the main binding acid mucopolysaccharide in the lesion is acid mucopolysaccharide which is none of the following: keratan sulfate, heparan sulfate, heparin, or chondroitin sulfate A, B or C. It is presumed that the main ⁶⁷Ga binding acid mucopolysaccharide is keratan polysulfate (or other oversulfated acid mucopolysaccharides).