Scintigraphic evaluation of two cases with alveolar soft part sarcoma

Two cases of alveolar soft part sarcoma were examined with gallium-67 citrate (67Ga), technetium-99m-methylenediphosphate (99mTc-MDP) and technetium-99m(V)-dimercaptosuccinic acid (Tc(V)-DMS) to compare the sensitivity of these three radiopharmaceuticals. All scintigrams were positive with primary tumor, and images with Tc(V)-DMS were the best. Skull metastasis could be also detected by all agents, but scintigrams with lung metastases were negative. In scintigraphic evaluation of alveolar soft part sarcoma, Tc(V)-DMS may be a better agent than 67Ga or 99mTc-MDP.     

Imaging of head and neck tumors with technetium(V)-99m DMSA. A new tumor-seeking agent

Tumor scintigraphy, using Tc(V)-99m DMSA was performed on 76 patients with head and neck tumors. In 32 cases, SPECT also was performed. Tc(V)-99m DMSA was found to have a sensitivity of 75% (56 cases), a specificity of 85% (20 cases) and an accuracy of 78% on planar imaging. ECT studies showed accumulation of Tc(V)-99m DMSA in all 25 malignant cases studied. However, in benign tumors, four of seven cases (57%) showed radionuclide uptake. Tc(V)-99m DMSA has superior physical properties to Ga-67 and could be of use in the diagnosis of head and neck tumors.     

Images of liposarcoma using technetium-99m bleomycin and technetium (V)-99m DMSA

The effectiveness of Tc-99m bleomycin (BLM) and Tc(V)-99m DMSA are compared with that of Ga-67 citrate, which is currently the most widely used agent. In four patients with lipomatous tumors, the clinical significance of tumor imaging with each of these three agents is discussed and compared. Results indicate that both Tc-99m BLM and Tc(V)-99m DMSA are superior in detecting the extension or localization of liposarcomas.     

Search for polynuclear pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS] tumour localization mechanism. I. Medullary thyroid carcinoma animal model.

To search for the tumour localization mechanism of Tc(V)-DMS, a polynuclear pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS], the development of medullary thyroid carcinoma (MTC) bearing mouse model was considered. Subcutaneously transplanted tumour was allowed to grow for 2, 4 and 6 weeks, and the influence of the tumour stage on the biodistribution of Tc(V)-DMS was screened. High radioactivity uptake in the tumour tissue was observed, and this accumulation showed a direct correlation with tumour growth and calcitonin secretion, the MTC marker detectable in the blood serum. The gathered data implicated some calcitonin-related factors as the mediator in the Tc(V)-DMS localization; participation of a phosphate-like oxoanion, TcO4(3-), is strongly suggested not only by the high radioactivity accumulation in the calcitonin-producing tumour but also by the accumulation in the bones of this model animal.     

Neuroblastoma: imaging evaluation by sequential Tc-99m MDP, I-131 MIBG, and Ga-67 citrate studies

Fourteen children with histopathologically confirmed neuroblastoma underwent sequential correlative imaging studies using I-131 MIBG, Tc-99m MDP, and Ga-67 citrate during various stages of the disease. Of the patients 86% showed I-131 MIBG accumulation in the primary tumoral site, whereas 71% showed Tc-99m MDP and 79% Ga-67 citrate uptake. In 86% at least one of the two latter radiopharmaceuticals concentrated in the primary tumor. The use of all three radiopharmaceuticals raised the detection rate to 93%. Of the osseous or extraosseous metastases 100% were detected by Tc-99m MDP studies. The I-131 MIBG studies were positive in 71% of the osseous metastases and in 70% of the extraosseous metastases. No Ga-67 citrate uptake was demonstrated in osseous metastases, although one extraosseous lung metastasis concentrated this radiopharmaceutical. Tc-99m MDP bone imaging was the best method for diagnosing metastatic spread of the disease and for monitoring the results of treatment. Primary tumor uptake was best indicated by I-131 MIBG. Both Ga-67 citrate and I-131 MIBG were superior to Tc-99m MDP with regard to accurately demonstrating the extent of primary tumors. Only Tc-99m MDP indicated the relationship of these tumors to the kidneys and neighboring osseous structures, providing early screening of kidney compression. Ga-67 citrate study was mainly indicated in tumors with catecholamine depletion, which failed to concentrate the other two radiopharmaceuticals. I-131 MIBG proved especially useful in detecting neuroblastoma with negative Tc-99m MDP and Ga-67 citrate studies and also proved to be helpful with those cases in which I-131 MIBG was planned for therapy. The following strategy is suggested for evaluating neuroblastoma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tc-99m-methylene diphosphonate (Tc-99m MDP) and Ga-67 concentration in soft tissue malignant fibrous histiocytoma (MFH): Case report

A case of calcifying soft tissue malignant fibrous histiocytoma (MFH) which showed a concentration of Tc-99m MDP and Ga-67 citrate, is presented. Tc-99m MDP and Ga-67 citrate scintigraphies of the thigh mass were correlated with conventional radiography, computed tomography (CT) and angiography.     

Search for polynuclear pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS] tumour localization mechanism

To search for the tumour localization mechanism of Tc(V)-DMS, a polynuclear pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS], the development of medullary thyroid carcinoma (MTC) bearing mouse model was considered. Subcutaneously transplanted tumour was allowed to grow for 2, 4 and 6 weeks, and the influence of the tumour stage on the biodistribution of Tc(V)-DMS was screened. High radioactivity uptake in the tumour tissue was observed, and this accumulation showed a direct correlation with tumour growth and calcitonin secretion, the MTC marker detectable in the blood serum. The gathered data implicated some calcitonin-related factors as the mediator in the Tc(V)-DMS localization; participation of a phosphate-like oxoanion, TcO₄ ^3–, is strongly suggested not only by the high radioactivity accumulation in the calcitonin-producing tumour but also by the accumulation in the bones of this model animal.Offprint requests to: A. Yokoyama     

Is ECT imaging with Tc(V)-99m dimercaptosuccinic acid useful to detect lung metastases of osteosarcoma?

ECT imaging, using Tc(V)-99m dimercaptosuccinic acid [Tc(V)-DMS] was performed in two patients with lung metastasis of osteosarcoma, and the results were compared with those of CT scan. Clear accumulation of Tc(V)-DMS was recognized in all cases in the same area that CT scans demonstrated. Tc(V)-DMS was labeled under optimal pH 8, had very low SnCl2 concentrations, an equilibrium between a stable form and a dissociated form of anion TcO4(3-) structurally similar to PO4(3-), and was postulated for tumor uptake. Considering this proposed mechanism for Tc(V)-DMS uptake by tumor cells, ECT imaging using this tracer could be of use in the early detection of lung metastasis of osteosarcoma.     

Osteoblastic osteosarcoma of the mandible: findings on Tc-99m HMDP bone and Ga-67 citrate scintigraphy

A 25-year-old woman presented with a disturbance in the opening of her mouth 5 months before admission. On admission, painful swelling of the right preauricular region was revealed. Computed tomography (CT) demonstrated a soft tissue density mass around the right condylar process of the mandible. Tc-99m hydroxymethylene diphosphonate (HMDP) bone scintigraphy and Ga-67 citrate scintigraphy showed avid uptake in the mass. The tumor was histologically identified as an osteoblastic osteosarcoma of the right mandible. There are few reports of Ga-67 citrate scintigraphy findings of osteoblastic osteosarcoma of the mandible. The accumulation patterns on Tc-99m HMDP bone scintigraphy and Ga-67 citrate scintigraphy are possibly characteristic of osteoblastic osteosarcoma of the mandible.     

A transferrin-mediated uptake of gallium-67 by EMT-6 sarcoma. II. Studies in vivo (BALB/c mice): concise communication

The EMT-6 sarcoma-like tumor of BALB/c mice can be grown as a solid subcutaneous transplantable tumor in vivo or as a monolayer culture in vitro. We have studied the uptake of gallium-67 by this tumor growing subcutaneously on the backs of 6-week-old BALB/c mice. After i.v. administration of Ga-67 citrate, tumor uptakes were as high as any others reported for mouse tumors. Also, for unknown reasons, there was appreciable reduction in tumor uptake with increasing amounts of Ga-67 citrate, even in the microcurie range. Furthermore, when mouse serum is prelabeled with Ga-67 and then injected, the EMT-6 uptake is greater than with Ga-67 administered as citrate (p less than 0.02). We believe that the finding of avid Ga-67 uptake in vivo helps to establish this unique in vivo/in vitro tumor system as a valid experimental model for studies regarding the mechanism of Ga-67 accumulation by neoplastic tissue.     

Solitary muscular sarcoidosis: CT,MRI, and scintigraphic characteristics

Scintigraphy using gallium-67 (⁶⁷Ga) citrate and penvaralent technetium-99m dimercaptosuccinic acid {[^99mTc(V)]DMSA} and other radiological examinations were performed in three patients with solitary muscular sarcoidosis who had tumor-like muscular lesions. Although distinction from other invasive soft tissue tumors was difficult using plain and enhanced computed tomography and magnetic resonance imaging, marked uptake of⁶⁷Ga and moderate uptake of [^99mTc(V)]DMSA were shown at the sites of granulomatous inflammatory lesions of sarcoidosis. Both⁶⁷Ga and [^99mTc(V)]DMSA scintigraphy could be of value in the diagnosis and detection of distribution of granulomas of sarcoidosis in the soft tissue and in determining the appropriate region for biopsy.     

Comparative evaluation of technetium-99m glucoheptonate and gallium-67 citrate thoracic imaging in detection of mediastinal and hilar involvement in primary lung cancer

Fifty-two patients with proven primary lung cancer who were referred for mediastinoscopy were prospectively studied with Tc-99m glucoheptonate and Ga-67 citrate thoracic scintigraphy. Primary lung tumors concentrated Ga-67 in 92% of cases, compared to 88% for Tc-99m glucoheptonate. Mediastinoscopy confirmed the presence of mediastinal metastases in 23 patients. The sensitivity of Tc-99m glucoheptonate and Ga-67 scans for mediastinal involvement detection is respectively 52% and 83%, for a specificity of 100% (Tc-99m glucoheptonate) and 88% (Ga-67). Twenty-nine patients underwent thoracotomy after a negative mediastinoscopy. Hilar metastatic involvement was present in eight patients. The sensitivity and the specificity for detection of hilar involvement were respectively 63% and 95% for Tc-99m glucoheptonate and 88% and 78% for Ga-67. Although more specific than Ga-67 scan, Tc-99m glucoheptonate thoracic imaging cannot be recommended in the staging of lung cancer because of its low sensitivity in the detection of intrathoracic metastatic spread of primary lung carcinoma.     

Clinical evaluation of tumour imaging using 99Tc(V)m dimercaptosuccinic acid, a new tumour-seeking agent

Considering the favourable nuclear properties of 99Tcm over 67Ga, we have developed a new tumour-seeking agent, 99Tc(V)m dimercaptosuccinic acid (Tc(V)-DMSA). In order to evaluate the clinical usefulness of Tc(V)-DMSA scintigraphies, 492 patients were studied with Tc(V)-DMSA, and in some cases, where possible, the results were compared with conventional 67Ga citrate scintigraphies. There was a high degree of usefulness of Tc(V)-DMSA in patients with head and neck tumours, medullary thyroid carcinomas and soft tissue tumours. But in patients with carcinomas of the lung, liver and gastrointestinal tract, malignant melanoma and lymphoma, Tc(V)-DMSA was of no or little use.     

Detectability of metastatic bone tumor by Ga-67 scintigraphy

Ga-67 scintigrams in patients with malignant diseases sometimes reveal uptake of the tracer in the bone metastases. Detectability of Ga-67 scintigraphy for metastatic bone tumors and benign bone lesions was compared with that of Tc-99m bone scintigraphy. Countable bone metastases detected by bone scintigraphy were evaluated whether the lesion showed apparent, faint, or negative Ga-67 uptake. Of 47 lesions 23 (49%) showed apparent uptake and 17 (36%) showed negative uptake. On the other hand, of 71 benign bone lesions, only 7 (10%), mostly fracture/osteotomy, showed apparent uptake of the tracer. Uptake in the other benign lesions such as trauma of the ribs, spondylosis deformans, and arthrosis deformans was rather faint. In patients with multiple bone metastases, 9 patients (82%) out of 11 showed more prominent abnormal findings in Tc-99m MDP bone scintigraphy than in Ga-67 scintigraphy; that is, Ga-67 scintigraphy was not able to reveal all metastatic bone lesions. In patients with untreated or recurrent tumors, relation between Ga-67 uptake in the tumors and that in the bone metastases was evaluated. Of 7 patients with negative Ga-67 uptake in the primary tumors, 5 showed positive Ga-67 uptake in the bone metastases; that is, there seemed to be little relation between Ga-67 affinity to the primary tumors and that to the bone metastases. Mechanisms of the Ga-67 uptake in the bone metastases were discussed. Not only the tumor cells or tissues in the bone metastases but also bone mineral or osteoclasts might be the deposition sites of Ga-67.     

Skeletal affinity of Tc(V)-DMS is bone cell mediated and pH dependent

In spite of recent advances in bone cellular and molecular biology, there is still a poor correlation between these parameters and data obtained from bone scintigraphy. Diphosphonate derivatives radiolabelled with technetium-99m (Tc-BPs) have long been recognised as bone-seeking agents with an affinity for areas of active mineralisation. However, during clinical trials with a pH-sensitive tumour agent, the pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS] showed a noticeable osteotropic character only in bone pathologies (bone metastases, Pagets diseases) and lacked accumulation in normal mature bone. To decipher the osteotropic character of Tc(V)-DMS, a study at the cellular level was considered necessary. Moreover, to learn more about the role of Tc bone agents, acid-base regulation by bone tissue or cells was studied. First, biological parameters in body fluid were measured under systemic acidosis, induced by glucose administration, in normal and Ehrlich ascites tumour (EAT)-bearing mice. Then, in vivo biodistribution studies using Tc(V)-DMS or a conventional Tc-BP agent were carried out. The effect of glucose-mediated acidification on the skeletal distribution of the Tc agents in the mice provided valuable hints regarding the differential mediation of bone cells in skeletal tissue affinity for the agents. Thereafter, in vitro studies on osteoblast and osteoclast cells were performed and the comparative affinity of Tc(V)-DMS and Tc-BP was screened under diverse acidification conditions. Moreover, studies were also carried out on acid-base parameters related to the cellular uptake mechanism. Very specific pH-sensitive Tc(V)-DMS accumulation only in the osteoclastic system was detected, and use of Tc(V)-DMS in the differential detection of osteoblastic and osteoclastic metastases is discussed.Ueda Mayumi has sadly died since the completion of this article. Requiescat in pace.     

Single photon emission computed tomography using201Tl chloride in pulmonary nodules: Comparison with67Ga citrate and99mTc-labeled hexamethyl-propyleneamine-oxime

A single photon emission computed tomography (SPECT) with 201Tl chloride (Tl-201) was carried out prospectively in 50 patients with pulmonary nodules and its diagnostic value was compared with those of 67Ga citrate (Ga-67) and 99mTc-labeled hexamethylpropyleneamine-oxime (Tc-99m-HMPAO). Tl-201 SPECT provided 88% (early)-91% (delayed) sensitivity, 85% (early and delayed) specificity and 87% (early)-89% (delayed) accuracy. The sensitivity of the Tl-201 planar image was 56 (early)-62% (delayed), which was significantly lower than that of SPECT. Delayed SPECT images at 2 hour postinjection were more preferable to disclose the malignant pulmonary nodule than early SPECT images at 15 minutes postinjection. The application of SPECT with Ga-67 failed to improve the sensitivity of planar imaging for malignant pulmonary nodules. Tc-99m-HMPAO was concentrated in 62% of 13 patients with malignant pulmonary nodules, which was slightly higher than Ga-67 in 54% of 28 patients. In an analysis of the histologic types of lung cancer, the sensitivity of Tl-201 was not significantly different in all types. On the other hand, Ga-67 was positive only in 25% of 12 patients with adenocarcinoma. A combination of SPECT and Tl-201 is the best choice among routine scintigraphic techniques for depicting malignant pulmonary nodules. The Tl-201 SPECT image may play a complementary role in the characterization of pulmonary nodules which are revealed on a plain radiograph and computed tomography.     

Intense accumulation of gallium-67 citrate in pancreatic endocrine tumor

We report intense accumulation of gallium-67 (Ga-67) citrate in a pancreatic endocrine tumor. A 69-year-old woman was admitted because of cough, fever, and weight loss. An abdominal enhanced computed tomography (CT) scan revealed a large tumor located between the liver and pancreas as well as swollen paraaortic lymph nodes. Whole-body scintigraphy with Ga-67 revealed intense accumulation in the upper abdomen corresponding to the mass, as well as in the midabdomen and the mediastinal lesion. Percutaneous needle biopsy was performed, and the diagnosis was adenocarcinoma of the pancreas. The patient's condition deteriorated, and she died 2 months after admission. The pathological examination at autopsy revealed a pancreatic endocrine tumor. No report has described findings of Ga-67 citrate scintigraphy of pancreatic endocrine tumors. Pancreatic endocrine tumor should be included in a differential diagnosis when such scintigraphic findings are encountered.     

On clinical usefulness of Tl-201 scintigraphy for the management of malignant soft tissue tumors

The purpose of this study was to investigate Tl-201 as a tumor scanning agent in patients with malignant soft tissue sarcomas and to establish the sensitivity of this type of scintigraphy concerning local recurrences or metastases that may remain clinically suspected. Seventy-eight patients with malignant soft tissue sarcomas and 22 with benign soft tissue tumors were studied. Of these 78 malignant soft tissue sarcomas patients, the sensitivity of Tl-201(81.2%) was higher than that of Ga-67 (68.8%). Thirty-three out of 78 patients received a total of 95 consecutive scintigraphic follow-up examinations. Therapeutic effects was assessed by comparing the results of Tl-201 examinations with the clinical findings. Of these 33 patients, the therapeutic effects observed were as follows: complete remission 1, partial remission 8, progress of disease 1, and no remarkable change 23. Tl-201 scintigraphy has proved itself very useful not only in clinically detecting the malignant soft tissue sarcomas and in assessing therapeutic effects on these diseases, but also in assessing the follow-up patients with malignant soft tissue sarcomas.     

Ga-67 and Fe-59 distributions in mice

Tissue distributions of i.v.-injected Ga-67 citrate and [59Fe] ferric citrate were measured in normal mice and in lymphoid-tumor hosts. The study arose out of previously reported tissue-culture work showing marked transferrin stimulation of Ga-67 and Fe-59 uptakes by cultured cells from mouse lymphoid tumors. In vivo, however, no obvious correlation was found between Ga-67 and Fe-59 tissue distributions; indeed, Ga-67 showed high affinity for tumor tissue and low affinity for hemopoietic tissues, while for Fe-59 the reverse applied. Taken together, these comparisons of kinetics and distributions for Ga-67 and Fe-59 suggest that a tissue's avidity for Ga-67 is strongly influenced by other factors besides the cell population's capacity for transferrin interactions.     

The evaluation of the bone marrow accumulation of Ga-67 citrate

The bone marrow distribution of Ga-67 citrate may be influenced by various elements in serum. In order to make these points clear, 1,955 whole body images were reviewed on the relationship between the accumulation of bone marrow and laboratory examination data of each patients. Increasing accumulation in the bone marrow was determined as positive when the bones of lower extremities were deposited on the images, because these bones was not visualized in normal gallium image. Laboratory data of 20 patients without having bone marrow accumulation was used as control. The positive findings of bone marrow accumulation was observed in 38 patients (2%) including 23 malignancies and 15 benign disease. The malignant tumor infiltration to the bone marrow was demonstrated by bone marrow aspiration biopsy in 2 out of 7 patients with bone marrow accumulation of Ga-67. Seven out of 15 patients with benign disease were collagen disease such as aortitis syndrome or SLE. The values of hemoglobin, hematocrit, serum iron and creatinine clearance were significantly lower in the patients with positive findings in comparison with control. These results suggest that the lower level of serum iron and anemia may cause increasing bone marrow accumulation of Ga-67 citrate.