Akira Muranaka

Experimental study on tumor affinity of 201Tl-chloride

AbstractThe 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.

Deposition of small 99mTc-labelled colloids in bone marrow and lymph nodes

The degree of deposition of small-particle colloids such as 99mTc-antimony sulfide colloids (ASC-group) and 99mTc-rhenium colloid (Tc-Re) in the bone marrow and lymph node was studied. H-ASC that was prepared in our laboratory was concentrated to a higher degree both in the bone marrow and lymph nodes, compared with other colloids.The H-ASC were mostly from 5 to 12.5 nm and the shape was uniform and spherical. The degree of deposition of Tc-Re in rabbit lymph nodes was not higher, however, the label was considered to be valuable clinically. The degree of deposition of Tc-Re in the bone marrow was not satisfactory. The size of Tc-Re was much smaller than H-ASC, ranging from 3 to 5 nm. From these results, it is considered that factors affecting deposition in the marrow are not identical to those in the lymph nodes.

Usefulness of bone imaging in diagnosis of sternocostoclavicular hyperostosis.

Four Patients with sternocostoclavicular hyperostosis showing characteristic abnormal uptake on bone imageing are described Bone imaging was useful in the diagnosis of sternocostoclavicular hyperostosis.

The usefulness of bone-marrow scintigraphy in the detection of bone metastasis from prostatic cancer.

We used a combination of bone and bone-marrow scintigraphy to study 25 patients with prostatic cancer. Of the 18 cases whose 99mTc-methylene diphosphonate (MDP) bone scans showed hot spots in the lower lumbar region of the spine and/or the pelvic bone, 8 had normal bone-marrow scintigrams. These 8 patients were subsequently shown to have senile, degenerative changes of the spine. On the other hand, in 9 of the 10 patients whose bone-marrow scintigrams showed accumulation defects, follow-up study and characteristic X-ray findings confirmed the presence of metastases. In all 6 cases with extensive bone metastases shown by 99mTc-MDP bone scintigraphy, 99mTc-sulphur-colloid bone-marrow scintigraphy showed multiple accumulation defects. In conclusion, bone-marrow scintigraphy was found to be useful in distinguishing metastatic lesions from benign degenerative changes in the cases with suspected bone involvement, as well as in evaluating equivocal lesions in the pelvis.We used a combination of bone and bone-marrow scintigraphy to study 25 patients with prostatic cancer. Of the 18 cases whose 99mTc-methylene diphosphonate (MDP) bone scans showed hot spots in the lower lumbar region of the spine and/or the pelvic bone, 8 had normal bone-marrow scintigrams. These 8 patients were subsequently shown to have senile, degenerative changes of the spine. On the other hand, in 9 of the 10 patients whose bone-marrow scintigrams showed accumulation defects, follow-up study and characteristic X-ray findings confirmed the presence of metastases. In all 6 cases with extensive bone metastases shown by 99mTc-MDP bone scintigraphy, 99mTc-sulphur-colloid bone-marrow scintigraphy showed multiple accumulation defects. In conclusion, bone-marrow scintigraphy was found to be useful in distinguishing metastatic lesions from benign degenerative changes in the cases with suspected bone involvement, as well as in evaluating equivocal lesions in the pelvis.

A case of synovial sarcoma with bone metastasis identified by bone marrow scintigraphy.

In a patient with synovial sarcoma, routine bone survey showed no abnormality, while bone marrow scintigraphy with Tc-99m sulfur colloid revealed a defect in the fifth lumbar vertebra. At surgery, tumorous invasion was noted in the fifth lumbar vertebra and the surrounding tissues. It was suggested that the bone marrow scintigraphy was particularly useful in the detection of tumorous invasion into the bone marrow at the early stage before the destruction of skeletal tissue.

99mTc-colloid kits from the view point of the accretion in the bone marrow — with special reference to comparison with 198Au-colloid —

With 9 kinds of available 99mTc-colloid kits for RES imaging, especially from the aspect of RES imaging of the bone marrow, observations were conducted on pH, the presence of free 99mTcO4-, labelling efficiency, rabbit blood clearance, the uptake in RES, urinary excretion, as well as the scintigraphy with rabbits and clinical cases. Compared to 198Au-colloid, marrow to liver ratio was found to be about the same, but its uptake to the spleen and liver was greater. In particular its urinary excretion was much more marked than 198Au-colloid, and in clinical use the bladder was more often delineated. This fact seems to suggest that it is desirable to develope a 99mTc-colloid more suitable for the bone marrow scintigraphy.

Uptake and excretion of 67Ga-citrate in malignant tumors and normal cells

Using in vivo and in vitro experimental models, the uptake and excretion of 67Ga-citrate in tumor cells and normal cells were studied. The timelapse accumulation of 67Ga in the tumor of rats bearing Yoshida sarcoma reached its peak 24 h after the administration of 67Ga and gradually decreased thereafter. However, the excretion of 67Ga from the tumor was less than that from normal lung. For culture cells in vitro, the uptake of 67Ga increased with lapse of contact time between 67Ga and the cells, but there was no distinct difference between the results for tumor cells and normal skin fibroblasts. The excretion of 67Ga from the cells tended to decrease with prolongation of the contact time, the excretion from tumor cells being only about 10% after a contact time of 24 h. This indicated a significant delay in excretion in comparison with that of normal skin fibroblasts. This delay in the excretion of 67Ga may be an important factor in the tumor accumulation of 67Ga.

Lymphoscintigraphy by SC injection of 67Ga-citrate

Lymphoscintigraphy with SC injection of 67Ga-citrate was carried out on patients with lymph node metastasis and malignant lymphoma. The dose given at each injection site was about 200 μCi and scintigraphy was started about 5 min after injection. Metastatic lymph nodes and malignant lymphoma were successfully imaged. This positive delineation corresponded well to cold lesions detected by lymphoscintigraphy with 99mTc-rhenium colloid in metastatic lymph nodes. Hotter lesions in malignant lymphoma were scanned positively with 99mTc-rhenium colloid by this method. In in vitro studies, incorporation of 67Ga-citrate in HeLa S3 cells was about 4 times that in macrophages, when the incubation time was 1 h, while colloidal uptake by macrophages was 13 times that by HeLa S3 cells. The binding of 67Ga to transferrin in lymph and pinocytosis are suggested mechanisms of localization. A combination of colloid-and sc 67Ga-lymphoscintigraphy would be of value in the diagnosis of lymph node disease.

Role of FeCl3 in 67Ga uptake by HeLa S3 cells in vitro.

The effect of FeCl3 on 67Ga uptake by HeLa S3 cells was studied in vitro. Uptake of 67Ga by HeLa S3 cells was influenced by the concentration of serum in the medium and especially that of transferrin added to the medium. Therefore, it is assumed that a mechanism of 67Ga uptake exists mediated by transferrin. However, when 10-2–10-1 mM FeCl3 was added to the medium in the same experimental system, a remarkable increase of 67Ga uptake was noted. Results of equilibrium dialysis, showed that binding of 67Ga to transferrin was inhibited by the administration of FeCl3. Moreover, the formation of a complex of 67Ga and FeCl3, which did not pass through the cellulose membrane, was observed. A correlation was found between an increase in 67Ga uptake by HeLa S3 cells and the formation of the 67Ga−Fe complex. These results indicate that another mechanism of 67Ga accumulation, namely the formation of a 67Ga−Fe complex plays a role in the uptake of 67Ga by tumor cells in the presence of iron.

Experimental and clinical studies on differential diagnosis of bone diseases with nucleomedical procedures.

This report is a study of the differential diagnosis of bone diseases using nucleomedical procedures. Experimental and clinical studies on the accumulation of 201Tl and 67Ga in bone inflammation and bone tumors were performed. Also, the degree of deposition of 99mTc-phosphorous compounds represented as a color difference was evaluated for a differentiation between malignant and benign diseases of the spine and shoulder. Uptake of 201Tl in inflammation of the spine and in tumor of the pelvis of rabbits was very low, while that of 67Ga was high. Uptake of 67Ga decreased gradually with lapse of time after the onset of inflammation. These experimental results agreed with clinical studies. The detectability of malignant tumors with 201Tl was inferior to that with 99mTc-label and 67Ga, although osteolytic lesions were occasionally 201Tl-positive. In terms of color range, the difference was 2 or less in spines of normal subjects and 3 or more in the metastatic bone disease and compression fracture. This difference was not statistically significant. Since 67Ga scan was occasionally negative in compression fracture, a differentiation was considered to be possible in such a case. A combined study of bone imaging with 99mTc-phosphorous compound including color difference, 67Ga imaging, bone-marrow imaging and radiography are considered to be helpful for the differentiation.