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.     

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.     

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.     

Gallium-67 scanning for carcinoma of the lung

Gallium-67 citrate scanning was prospectively evaluated in 55 patients who had lung lesions suspected to be primary carcinoma on chest x-ray films and in whom subsequent histologic diagnosis was obtained. Of 47 patients with histologically proved carcinoma of the lung, 44 (94 per cent) had a positive 67Ga scan. No patient with a positive scan had a benign lesion, so that the positive scan accuracy rate was 100 per cent. All 8 patients with a benign lesion and 3 patients with a malignant lesion had negative scans, for a negative scan accurary rate of 72 per cent for benign lesions. These results give statistical validity for the usefulness of the 67Ga scan in diagnosing carcinoma of the lung (p less than 0.001). Tumor cell type had little effect on the sensitivity of 67Ga scan. The 67Ga scan was equally useful in the evaluation of peripheral and central lesions. There was little difference amount T1, T2, and T3 classified lesions in their ability to take up 67Ga. The 67Ga scan was competitive with mediastinoscopy in assessing mediastinal lymph node metastases and provides a noninvasive method of assessing hilar lymph node metastases. There was a good correlation between the clinical staging of patients with lung cancer based on a chest x-ray film and 67Ga scanning and the staging after surgical treatment based on the histology of the resected specimens.     

Prospective study of bacteremia rate after elastic band ligation and sclerotherapy of esophageal varices in patients with hepatosplenic schistosomiasis

Bone scintigraphy was performed in a 69-year-old male patient with adult T-cell leukemia suffering from right lower limb pain. Numerous sites of increased uptake were seen in the skull, left clavicle, bilateral humeri, bilateral radii and right femur and tibia. Bone radiographs showed multiple osteolytic lesions, most of which corresponded to the abnormal deposits on the bone scans with 740 MBq of 99mTc-hydroxymethylene diphosphonate. This pattern is rarely reported, but bone involvement of adult T-cell leukemia is not uncommon. Bone involvement was remarkable on the appendicular skeleton when compared with common metastatic bone tumors. Bone scintigraphy may be useful in detecting bone involvement in adult T-cell leukemia.     

Primary adrenal lymphoma: gallium scintigraphy and correlative imaging

Primary adrenal lymphoma is a rare entity, with only 16 cases reported in the last 40 yr. Although 67Ga scintigraphy has been extensively used to evaluate patients with other types of lymphomas, there are no reports of its use in patients with this disease entity. A man with primary adrenal lymphoma and no evidence of extraadrenal spread who was evaluated from presentation to remission with gallium scintigraphy and CT is presented. Gallium scintigraphy was valuable in assessing response to therapy.     

The role of 99mTc-sestamibi and other conventional radiopharmaceuticals in breast cancer diagnosis

The wide availability and the extensive use of screening mammography have resulted in an earlier diagnosis of breast cancer and in a significant reduction in the relative risk of dying from this disease. Despite technical improvements and major advantages associated with the use of mammography (and breast ultrasound), this procedure has some limitations in clinical practice, especially in women with dense breast tissue, implants, severe dysplastic disease, or significant architectural distortion following breast surgery or radiation therapy. Different noninvasive imaging techniques have been evaluated to overcome these limitations. Nuclear medicine also has been actively involved in the detection of breast cancer, using various types of radiopharmaceuticals. Currently, there are three radiotracers commonly used for breast imaging or scintimammography in either clinical practice or research: 99mTc-sestamibi and 99mTc-tetrofosmin (two agents used for myocardial perfusion imaging) and 99mTc-MDP (methylene diphosphonate, used for bone scintigraphy). 99mTc-sestamibi was the first radiopharmaceutical to be approved by the FDA for scintimammography. Several prospective studies have shown that the overall sensitivity of 99mTc-sestamibi scintimammography in detection of breast cancer was 85%, the specificity was 89%, and the positive and negative predictive values were 89% and 84% respectively. Similar numbers have been demonstrated for 99mTc-tetrofosmin and 99mTc-MDP scintimammography. Although not indicated as a screening procedure for the detection of breast cancer, scintimammography may play a useful and significant role in various specific clinical indications such as nondiagnostic or difficult mammography, and evaluation of high-risk patients, tumor response to chemotherapy, and axillary lymph node metastatic involvement.     

Studies on groundnut proteins: Part VII--Physico-chemical properties of conarachin II

A series of 183 patients suffering from cancer examined with 99mTc-yrophosphate scintigraphy is presented. Of the 74 cases with radiologically confirmed metastases or primary tumour in the skeleton 67 (91%) had an isotope accumulation. Four cases with false positive accumulations were detected. In three cases the uptake disappeared subsequently, in the fourth the uptake persisted, all patients being at least on year without any osseal symptoms. Even when the 99mmTc-pyrophosphate scintigraphy is recommended as the first diagnostic measure in skeletal lesions, the scintigraphy alone is not sufficient for deciding the treatment of a cancer patient.     

A case of malignant lymphoma of the thyroid accompanied by interstitial pneumonitis during radiation therapy after systemic chemotherapy

We reported a case of malignant lymphoma of the thyroid accompanied by interstitial pneumonitis during radiation therapy after systemic chemotherapy. Thyroid malignant lymphoma is a rare malignant tumor, which usually responds well to irradiation and systemic chemotherapy. Interstitial pneumonitis occurred during radiation after systemic chemotherapy. In this case, irradiation was simultaneously done with the chemotherapy. The radiation field included the neck and upper mediastinum. Chest X-ray showed multiple patchy shadows in both the middle and lower lung field, and it changed to contraction shadows after steroid pulse therapy. 67Ga scintigram showed multifocal increase of uptake, when chest X-ray patchy shadows were seen only in the middle and lower lung fields. 67Ga scintigraphy and CT were considered useful for evaluation of drug-induced interstitial pneumonitis.     

Detection of bone metastases in breast cancer by 18FDG PET: differing metabolic activity in osteoblastic and osteolytic lesions

PURPOSE: 99mTechnetium methylene diphosphonate (99mTc MDP) bone scintigraphy is currently the method of choice for the detection of bone metastases, but 18F-fluoro-deoxy-D-glucose positron emission tomography (18FDG PET) offers superior spatial resolution and improved sensitivity. We have compared 18FDG PET with 99mTc MDP bone scintigraphy in patients with skeletal metastases from breast cancer and have analyzed the data in subgroups based on radiographic characteristics of lesions. PATIENTS AND METHODS: Twenty-three women with breast cancer and confirmed bone metastases were studied with both 99mTC MDP bone scintigraphy and 18FDG PET, and the number of lesions detected and the quantitation of uptake (standardized uptake values [SUVs]) of 18FDG in osteolytic and osteoblastic metastases were compared. Survival was compared for both lytic and blastic bone metastases and for patients with high and low accumulation of 18FDG. RESULTS: 18FDG PET detected more lesions than 99mTc MDP scintigraphy (mean, 14.1 and 7.8 lesions, respectively; P < .01). However, 18FDG detected fewer bone metastases compared with 99mTc MDP scintigraphy in a subgroup of patients with osteoblastic disease (P < .05). Higher SUVs were observed for osteolytic than osteoblastic disease (mean, 6.77 and 0.95, respectively; P < .01). Survival was lower in patients with osteolytic disease compared with the remainder (P=.01). A difference in survival was not found for those patients with high SUVs (> 3.6; P=.4). CONCLUSION: 18FDG PET is superior to bone scintigraphy in the detection of osteolytic breast cancer metastases, which led to a poorer prognosis. In contrast, osteoblastic metastases show lower metabolic activity and are frequently undetectable by PET. The biologic explanation for this observation remains to be elucidated.     

Thyroid scintigraphy in patients with thyroid tumors using 99mTc-hexakis 2-methoxy isobutyl isonitrile

Early and delayed thyroid scintigraphy with 99mTc-hexakis 2-methoxy isobutyl isonitrile (99mTc-MIBI) was performed in 18 patients with thyroid tumor, including 8 with papillary carcinoma, 1 each with follicular carcinoma, anaplastic carcinoma, and malignant lymphoma, and 7 with thyroid adenoma. Scintigrams obtained were compared with those taken with other radionuclides. In all 11 patients with malignant tumors, increased 99mTc-MIBI uptake was noted in the tumors on early images, although anaplastic carcinoma and malignant lymphoma had mild uptake. On delayed images, 99mTc-MIBI washout was noted in 45.4% (5/11). In one patient with extensive cervical lymph node metastasis, 99mTc-MIBI concentration was evident in the metastatic foci. In the 4 where, the thyroid adenoma consisted mainly of cystic degeneration, a focal defect was noted, but two of the three patients whose thyroid adenoma consisted mainly of a solid component had an intense tracer uptake in the tumors on early and delayed images. In conclusion, there were increased 99mTc-MIBI accumulations in all of the 14 solid thyroid tumors. The quality of 99mTc-MIBI scintigraphic images of thyroid tumors was equal or slightly superior to that taken with 201Tl scintigraphy. 99mTc-MIBI thyroid scintigraphy may be useful in detecting a solid thyroid tumor and its metastasis, although it cannot be used to differentiate between benign and malignant tumors.     

Health insurance coverage and outcome following acute myocardial infarction. A community-wide perspective

The potential of scintigraphy with technetium 99m-labelled J001 (99mTc-J001) to detect synovitis was studied in 15 rabbits with osteoarthritis (OA) of the right knee (section of cruciate ligaments), in five sham-operated rabbits and in four non-operated rabbits. J001 is a non-pyrogenic, acylated poly (1,3) galactoside isolated from the membrane of a non-pathogenic strain of Klebsiella pneumoniae which is able to bind selectively to macrophages via the binding to CD11b and CD14 molecules. The results of 99mTc-J001 scintigraphy were compared with those of scintigraphy with 99mTc-labelled methylene diphosphonate (99mTc-MDP) and GC-APG (a derivative of J001 unable to bind macrophages in vitro). The mean scintigraphic ratios (diseased healthy knee) of 99mTc-J001 were significantly higher in OA rabbits than in sham- and non-operated rabbits, from as early as day 18 until day 90. 99mTc-J001 scintigraphy demonstrated earlier increased uptake than 99mTc-MDP scintigraphy. The mean scintigraphic ratios of 99mTc-J001 were significantly higher than those of 99mTc-GC-APG (which remained normal) in OA rabbits. The normal scintigraphic ratios of 99mTc-J001 in sham-operated and non-operated rabbits, as well as of 99mTc-GC-APG in OA rabbits, suggested that the increased uptake demonstrated with 99mTc-J001 in OA rabbits, as early as day 18 corresponded to imaging of synovitis via elective macrophage targeting. These results showed that 99mTc-J001 scintigraphy should be a specific method of detecting synovitis in OA.     

Gallium-67 radiotoxicity in human U937 lymphoma cells

Promising clinical results have been obtained with radiolabeled antibodies in lymphoma patients. The higher uptake by lymphomas of 67Gallium (67Ga) compared with monoclonal antibodies makes selective radiotherapy by the widely available 67Ga appealing. However, the gamma radiation of 67Ga used in scintigraphy is considered to be almost non-toxic to lymphoma cells. However, in addition to photon radiation 67Ga emits low energy Auger electrons and 80-90 keV conversion electrons which could be cytotoxic. The objective of the present study was the assessment of radiotoxicity of 67Ga on a lymphoid cell line: U937. Proliferation (MTT-assay) and clonogenic capacity (CFU-assay) were measured after 3 and 6 days incubation with 10, 20 and 40 microCi ml-1 67Ga. Growth inhibition was 36% after 3 days incubation and 63% after 6 days incubation with 40 microCi 67Ga ml-1. Clonogenic capacity was reduced by 51% after 3 days and 72% after 6 days incubation with 40 microCi ml-1 67Ga. A survival curve showed an initial shoulder and became steeper beyond 200-250 pCi cell-1 (low linear energy transfer type). Iso-effect doses of 67Ga and 90Yttrium (90Y) were determined. The iso-effect dose of 40 microCi 67Ga ml-1 (cumulative dose of conversion electrons 306 cGy) was 2.5 microCi 90Y ml-1 (cumulative dose 494 cGy) and the iso-effect dose of 80 microCi 67Ga ml-1 was 5.0 microCi 90Y/ml. The main cytotoxic effect of 67Ga seems to be induced by the 80 keV conversion electrons. We conclude that the conversion electrons of 67Ga have a cytotoxic effect on U937 cells and that in our experiments a 16-fold higher microCi-dose of 67Ga than of 90Y was needed for the same cytotoxic effect. We believe that 67Ga holds promise for therapeutic use.     

Breast involvement in non-African Burkitt''s lymphoma

A patient with non-African Burkitt's lymphoma is reported in whom bilateral breast involvement was detected by both mammography and 67-Ga-citrate scintigraphy. The causes of breast uptake of 67Ga-citrate are reviewed, and it is noted that not only asymmetrical increases in uptake of 6767Ga-citrate are indicative of disease.     

Academic associate program: integrating clinical emergency medicine research with undergraduate education

MATERIALS AND METHODS: The diagnostic accuracy of scintimammography with 99mTc-MDP was evaluated in 400 consecutive women with clinical or mammographic suspicion of breast cancer, candidate to surgery and/or excisional biopsy. Lateral views of both glands were acquired, in prone position, 5-10 min after the injection of 550-740 MBq of 99mTc-MDP. The scintigraphic results were compared to mammograms and classified using the histological findings as gold standard. RESULTS: Mammography was suggestive for cancer in 231 (57%), suspicious in 49 (12%) and indeterminate in 120 (31%) patients. Breast carcinoma was histologically proven in 330 women, benign breast diseases in 70. The tumor size ranged from 4 x 5 to 50 x 60 mm. 99mTc-MDP visualized as foci of increased uptake 305/330 cancers (92%). In particular, in women with indeterminate mammograms the SMM had a diagnostic accuracy of 84%, correctly characterizing 101/120 lesions. Twenty missed cancers had largest diameter < or = 10 mm, 5 < or = 15 mm. Lack of 99mTc-MDP uptake occurred in 64 out of 70 benign lesions. These lesions were classified as truly negative. Conversely, 3 fibroadenoma and 3 epithelial hyperplasia with moderate or severe atypia were falsely positive. The overall specificity was 91.5%; the accuracy was 92%, the positive and negative predictive values were respectively 98% and 72%. CONCLUSIONS: The results obtained in this study suggest that 99mTc-MDP scintimammography accurately detects breast carcinomas with largest diameter > 10 mm; it differentiates malignant from benign lesions, and it shows promising insights in characterizing breast abnormalities mammographically indeterminate.     

In-111 monoclonal antibody versus Ga-67 citrate and Tc-99m SC subtraction in a patient with malignant melanoma

Gallium-67 is routinely used for follow-up of patients with malignant melanoma. However, its nonspecificity for melanoma and its high rate of false-positive results have always been a matter of concern. The authors describe a patient who encountered serious problems with the use of gallium. Because gallium is taken up well by the liver and by melanoma, results of gallium scintigraphy of the liver may appear normal even if there is metastatic disease. In this patient, results of gallium scintigraphy of the liver were negative for metastasis but revealed extrahepatic foci detected by the monoclonal antibody. Computed tomography showed areas of attenuation, revealing only a few intrahepatic tumors and no extrahepatic disease. Tc-99m SC revealed intrahepatic metastases, but no extra-hepatic metastases were seen. A monoclonal antibody (ZME-018) scintigram did reveal hepatic metastases along with probable small, extrahepatic, metastatic foci. Overall hepatic uptake of the monoclonal antibody was relatively low. An image subtraction algorithm was devised whereby the sulfur colloid image was subtracted from the gallium scintigram. The resultant image revealed both the intrahepatic and extrahepatic metastases seen on the ZME-018 images. It is likely that in the past many hepatic metastases have been missed because Tc-99m SC images have not been routinely used as part of melanoma management protocols. The uptake of the ZME-018 by the tumor was significantly higher than that of the normal liver, suggesting that ZME-018 labeled with the appropriate emitter may be an effective specific therapeutic tool in selected 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.     

Relationship between symptoms of jumper''s knee and the ultrasound characteristics of the patellar tendon among high level male volleyball players

In this study we investigated the applicability of 99mTc-labeled CD19 monoclonal antibody (mAb) for tumor imaging in patients with B cell non-Hodgkin's lymphoma. A 1-mg sample of murine CD19 mAb was labeled with approximately 550 MBq [99mTc]pertechnetate. The labeled mAb was administered i.v. to seven patients, four without and three with pretreatment with 10 mg unlabeled CD19 mAb. The number of circulating B cells was decreased by 44 +/- 5% 1 h after injection of the radiolabeled mAb. Peripheral B cells were coated with CD19, resulting in partial modulation of CD19, most pronounced in the three pretreated patients. Whole-body images were obtained with a gamma camera and compared with results obtained by conventional imaging techniques. Initially, blood-pool activity dominated, whereas 24 h after injection the radioactivity was mainly located in the spleen, kidneys and liver. In two patients, a lesion in the spleen appeared as an unlabeled spot. In one patient, a lesion in the femur, which was detected by computed tomography (CT) and gallium-67 scans, was also seen on the CD19 scan from 1 h after administration of the radioimmunoconjugate onwards. Good imaging of bone marrow infiltration was observed in one of three patients. Lymph node involvement was not observed in any of the patients in whom affected lymph nodes were detected by CT or gallium-67 scan. In conclusion, in the present study radioimmunodetection with 99mTc-labeled CD19 mAb was found to be inferior to CT and gallium-67 scanning in the diagnosis of patients with B cell non-Hodgkin's lymphoma.     

Fluorine-18-fluorodeoxyglucose PET identification of cardiac metastasis arising from uterine cervical carcinoma

Cardiac metastasis of uterine cervical carcinoma is rare. We describe a patient with a past history of uterine cervical carcinoma who presented with metastasis to the heart, lungs and distant lymph nodes 3 yr after surgery and chemotherapy. Since the patient complained of chest pain and demonstrated electrocardiogram abnormalities, we performed echocardiography, electron beam CT and MRI, which revealed a tumor in the right ventricular wall. The tumor was assessed by 67Ga scintigraphy and 18F-fluorodeoxyglucose (FDG) PET scanning. The mean differential 18F-FDG uptake ratio of the tumor was 7.9, suggesting malignancy, which was later confirmed by myocardial biopsy. Information about the extent of the tumor and partial necrosis within it was provided by 18F-FDG PET. Although both radionuclide imaging techniques also detected metastatic lesions in the lungs and lymph nodes, 18F-FDG PET scanning detected small lesions more sensitively than 67Ga scintigraphy.     

Three phase 99Tcm (V)DMSA scintigraphy in Paget's disease: an indicator of pamidronate effect

The use of three phase 99Tcm (V)DMSA scintigraphy is reported in a patient with Paget's disease of bone before and after intravenous pamidronate therapy. It was a useful modality for estimating the activity of Pagetoid lesions and the therapeutic effect of pamidronate, from a different aspect to bone scintigraphy. Three phase 99Tcm (V)DMSA scintigraphy evaluates both the blood flow and the metabolic activity of Pagetoid bone.