Gallium-67 citrate in cerebral infarction.

Cerebral scans were obtained on 30 "stroke" patients first with 99mTc pertechnetate and subsequently with 67Ga citrate. Of the 26 patients with abnormal 99mTc static scans, 17 (65%) showed the same abnormality in gallium citrate scans also. In 4 patients with positive technetium flow studies but negative static scans, no abnormality was seen in the scans obtained after gallium citrate injection. In none of the patients was the relative concentration of radioactivity in the lesion greater in the gallium image than in the technetium image. This study proves the nonspecificity of gallium citrate and thus its inability to differentiate cerebral tumor from cerebral infarction just on the basis of localization of gallium.     

Uptake of myocardial imaging agents by rejecting and nonrejecting cardiac transplants. A comparative clinical study of thallium-201, technetium-99m, and gallium-67

To study the scintigraphic detectability of cardiac rejection, we performed 135 planar myocardial scans ([99mTc]pyrophosphate, 85; 201Tl, 36; 67Ga, 14) together with endomyocardial biopsies in ten patients for a (mean) 17-mo postoperative period. Specificity of each agent exceeded 89%. Technetium-99m pyrophosphate showed results that significantly correlated with the severity of rejection (p = 0.03), as shown by biopsy, but neither 201Tl nor 67Ga did so (p = 0.63 and 0.81, respectively). Technetium-99m pyrophosphate showed better diagnostic accuracy (85%) than 201Tl (69%) and 67Ga (64%). Technetium-99m pyrophosphate also showed higher negative predictive value (91%) than thallium (76%) and gallium (69%). Thus, a normal 99mTc pyrophosphate scan was usually associated with absence of cardiac rejection. However, all three agents showed unacceptably poor sensitivity (0% to 30%) and thus were not useful as a screening test for cardiac rejection, even when the same agent was used serially in imaging a given patient.     

Chronic osteomyelitis: monitoring by 99mTc phosphate and 67Ga citrate imaging

Thirteen patients with chronic osteomyelitis, treated for 6 months with rifampin, had serial 99mTc phosphate and 67Ga scans to determine their value in assessing response to treatment. In patients who responded to treatment, gallium scans were deemed more accurate than 99mTc phosphate bone scans. The gallium scans, although still abnormal at the end of 6 months of antibiotic therapy, showed an improvement trend in all the responders except one in whom fracture recurred. Worsening or lack of improvement on gallium scans predicted active bone infection in five of six "clinical-failure" patients who had documented active bone infection. 67Ga scans eventually became normal in all patients who remained asymptomatic (excluding one with recurrent fracture). 99mTc phosphate scans became normal in only one of five clinical responders. All nonresponders had persistently abnormal scans, although after 6 months of therapy only four of seven showed worsening or no improvement on the scan. Therefore, 67Ga is preferred over 99mTc phosphate bone scans in the assessment of response to therapy in chronic bone infection. Clinical utility of the gallium scan is most significant in patients whose clinical assessment is uncertain, but routine use of this technique does not appear to be warranted. Gallium images are most valuable when obtained over a period of time, so that the trend of improvement versus nonimprovement is evident.     

Hematogenous pyogenic vertebral osteomyelitis: diagnostic value of radionuclide bone imaging

Hematogenous pyogenic vertebral osteomyelitis (HPVO) continues to be a diagnostic problem for clinicians due to nonspecific presentation of the disease (1,2). We reviewed our experience of the last 10 years to determine the diagnostic usefulness of radionuclide bone studies in this disease. We found 15 patients whose primary diagnosis was HPVO. Of the 15 patients, 12 had [99mTc]MDP bone scans which were all positive. Five of the 12 patients had positive [67Ga]citrate scans and one patient with chronic active HPVO had negative 67Ga and [111In]WBC bone images. At the same time, three patients' spine x-rays and one patient's CT scan of the vertebra were normal. Additionally, in three patients spine x-rays were interpreted as consistent with degenerative joint disease that contributed to the delay of the diagnosis. We conclude that when HPVO is suspected an abnormal [99mTc]MDP bone image increases the probability of the disease, even if the x-rays and CT scans of the spine are normal. An abnormal 67Ga image following an abnormal 99mTc bone image increases the specificity of the diagnosis. Normal [99mTc]MDP and [67Ga]citrate bone images of the vertebra virtually exclude the diagnosis of HPVO.     

The value of gallium-67 and thallium-201 whole-body and single-photon emission tomography images in dialysis-related beta 2-microglobulin amyloid

The aim of this study was to investigate the value of gallium-67 and thallium-201 whole-body and single-photon emission tomography (SPET) images in long-term dialysis patients in whom dialysis-related beta 2-microglobulin amyloid (beta 2-MA) was clinically suspected. Twenty-three patients who had received dialysis for at least 10 years were included in the study. A technetium-99m methylene diphosphonate (MDP) whole-body scan was performed in all of the patients. If there was any MDP accumulation in the articular and/or peri-articular region, 67Ga and 201Tl whole-body and SPET images were then acquired. If any 67Ga and/or 201Tl uptake was observed, a CT-guided biopsy was done. In those patients who had articular and/or peri-articular uptake of 99mTc MDP, 67Ga and/or 201Tl and who were pathologically proven to have beta 2-MA, 99mTc MDP, 67Ga and 201Tl whole-body scans and SPET were carried out again, both 3 months and 1 year after initiation of treatment. This served to evaluate the therapeutic effect and allowed comparison with the clinical findings. Of the 23 patients, eight had abnormal 99mTc MDP uptake. Among these eight, six had intense 99mTc MDP, 67Ga and 201Tl uptake in the articular and peri-articular regions before medication. Three months after the start of treatment, there were very marked decreases in uptake on both the 67Ga and 201Tl scans but less obvious changes in uptake of 99mTc-MDP. In comparison with the other clinical manifestations such as limitation in range of motion, the more the painful disability improved, the less was the uptake on both 67Ga and 201Tl scans. There were virtually no differences in uptake pattern between the three scans of each radiopharmaceutical obtained for each patient in both 3 months and 1 year after initial of treatment. It is concluded that 99mTc-MDP whole-body bone scan can both detect active and pre-existing inactive deposits of beta 2-MA. 67Ga and 201Tl scans are helpful to differentiate active from inactive deposits of beta 2-MA and to evaluate the therapeutic effect on these patients. SPET images are usually needed to distinguish articular and periarticular lesions from bone lesions.     

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.     

Technetium-99m HM-PAO-labeled leukocytes in detection of inflammatory lesions: comparison with gallium-67 citrate

Forty-three patients with suspected benign, inflammatory, or infectious diseases were imaged with [99mTc]HM-PAO-labeled leukocytes and [67Ga]citrate. Technetium-99m leukocytes showed 22 true-positive, no false-positive, 19 true-negative, and two false-negative findings and [67Ga]citrate 23, 7, 12 and 1, respectively. The sensitivity, specificity, and accuracy values with 99mTc leukocytes were 92%, 100%, and 95%, and with [67Ga]citrate 96%, 63%, and 81%. Technetium-99m leukocyte scintigraphy has a promising future in comparison with [67Ga]citrate because of the ready availability of [99mTc]HM-PAO, the good image quality, more rapid results (within few hours), and the lower radiation exposure to the patient with 99mTc leukocytes. The usefulness of 99mTc leukocytes in chronic osteomyelitis needs further evaluation.     

Evaluation of cold areas on the thyroid scan with 67Ga-citrate.

Cold areas on 131I or 99mTc thyroid scans were re-evaluated using 67Ga-citrate in 134 patients. In 62 patients surgical specimens were obtained for histologic studies. Of 46 benign lesions, all had negative 67Ga scans, and 67Ga scans in 5 of the 16 lesions judged to be malignant were positive. It was thought that the sensitivity of the method did not warrant its use for routine screening in evaluations of malignancy of thyroid nodules.     

Respiratory clearance of aerosolized radioactive solutes of varying molecular weight

To determine the influence of varying molecular weight (mol wt) on respiratory clearance of aerosolized solutes, we studied eight radiopharmaceuticals, each administered to four dogs: sodium 99mTc pertechnetate (TcO4), 99mTc glucoheptonate ([99mTc]GH), 51Cr-ethylenedinitrotetraacetate ([51Cr]EDTA), 99mTc diethylenetriaminepentaacetate ([99mTc] DTPA), 111In diethylenetriaminepentaacetate ([111In]DTPA), 67Ga desferoxaminemesylate ([67Ga]DFOM), 99mTc dextran ([99mTc]DX) and 111In transferrin ([111In]TF). After aerosolization (0.8 m MMD, 2.4 GSD), clearance was determined for 30 min and then corrected by intravenous injection for nonairspace radioactivity. In-TF clearance (0.11 +/- 0.10%/min) was lower than TcO4 (6.32 +/- 0.62%/min), [99mTc]GH (1.50 +/- 0.37%/min), [51Cr]EDTA (2.38 +/- 1.02%/min), [99mTc]DTPA (3.51 +/- 0.40%/min), [111In]DTPA (2.35 +/- 0.42%/min), [67Ga] DFOM (1.99 +/- 0.49%/min) and [99mTc]DX (1.81 +/- 0.75%/min) clearances (p less than 0.001). TcO4 clearance was higher than others (p less than 0.001). Technetium binding to DX was unsatisfactory; aerosolization caused unbinding from DTPA. We conclude that respiratory clearance of large mol wt solutes within 30 min is negligible and, that clearance of molecules between 347-5,099 daltons differs greatly, suggesting that binding and/or intrapulmonary retention affect transfer.     

Comparative uptake of 67Ga and 99mTc MDP in rabbits with a benign noninfected bone lesion (fracture)

Mid-shaft fractures of the radius and ulna were produced in 3 to 4 kg New Zealand white rabbits and quantitative uptake of 99mTc MDP and 67Ga determined at 11, 18, 25, 32, 51, and 78 days following fracture. Two hundred microCi of 67Ga was administered 24 hours prior to sacrifice and 1.5 mCi 99mTc MDP 2 hours prior to sacrifice. Specific activity ratios (SARs) were determined between fracture and control sides for bone, muscle and skin. SARs for bone were surprisingly similar for 99mTc MDP and 67Ga, reaching peak values of 6.07 +/- 0.64 (99mTc 18 days); 6.58 +/- 0.90 (67Ga 32 days), subsequently decreasing to minimum values at 78 days postfracture (99mTc MDP 2.25 +/- 0.14; 67Ga 2.18 +/- 0.08). There was no statistically significant difference in SAR for 99mTc MDP vs. 67Ga in bone at any time after fracture. Whole sections of limb were resected on selected animals and activity ratios determined for these sections as a function of the contribution of activity from the various tissues in the volume of interest. Total activity ratios of 67Ga were lower than bone SARs as a result of the contribution of activity from muscle and skin. Thus the apparent lower activity ratios noted on 67Ga images compared with 99mTc MDP images in this fracture model were not due to differences in bone SARs but rather due to the higher soft tissue background activity contribution in the 67Ga images.     

Comparison of quantitative 99mTc-HMPAO and 67Ga citrate lung scans in patients with active diffuse infiltrative lung disease

Diffuse infiltrative lung disease (ILD) is a heterogeneous group of disorders that predominantly affect the lung parenchyma and spare the airway. To objectively assess the degree of pulmonary vascular endothelium damage in active ILD, lung/liver uptake ratios (L/L ratios) on 99mTc hexamethylpropylene amine oxime (99mTc-HMPAO) lung scans were determined in 21 patients with active ILD. Meanwhile, the 67Ga citrate uptake index (GUI) on 67Ga lung scans was measured in order to evaluate the severity of lung inflammation in active ILD. The results show there were statistically significant differences between normal controls and patients with active ILD, as shown in the L/L ratio and GUI. However, when the patients were divided into two groups: (1) eight patients with normal chest X-ray findings, and (2) 13 patients with abnormal X-ray findings, there was no significant difference between groups 1 and 2 for the results of L/L ratio and GUI. In addition, no correlation between the degree of damage to the pulmonary vascular endothelium and the severity of lung inflammation was found. In conclusion, L/L ratios on 99mTc-HMPAO lung scans and GUI on 67Ga lung scans are different to the findings of chest X-rays and have the potential to objectively detect the degree of damage to the pulmonary vascular endothelium and the severity of lung inflammation in active IDL. However, the relationship between L/L ratio and GUI in active ILD is not significant.     

Radiolabeled, nonspecific, polyclonal human immunoglobulin in the detection of focal inflammation by scintigraphy: comparison with gallium-67 citrate and technetium-99m-labeled albumin

The accumulation of nonspecific polyclonal human immunoglobulin (IgG) radiolabeled with 125I or 111In was compared to that of [67Ga]citrate and [99mTc]albumin in rats with deep thigh inflammation due to Escherichia coli infection. Serial scintigrams were acquired at 1, 3, 24, and in some cases, 48 hr after injection. As early as 3 hr postinjection, [111In]IgG showed greater accumulation at the lesion than [99mTc]HSA (p less than 0.01). Both [125I]IgG and [111In]IgG showed greater accumulation than [67Ga]citrate (p less than 0.01). At 24 hr, IgG image definition increased, while HSA image definition decreased, and the intensity of accumulation of both IgG preparations was greater than that of [67Ga]citrate or [99mTc]HSA (p less than 0.01). At all imaging times, [67Ga]citrate accumulation was surprisingly low. In inflammation produced by Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, or turpentine, [111In]IgG accumulation was similar to the results obtained with Escherichia coli. These studies suggest that focal sites of inflammation can be detected with radiolabeled nonspecific human polyclonal IgG.     

Comparison of technetium-99m-HM-PAO leukocytes with indium-111-oxine leukocytes for localizing intraabdominal sepsis

Technetium-99m-HM-PAO [( 99mTc]HM-PAO) leukocyte and indium-111-oxine (111In-oxine) leukocyte scanning were carried out simultaneously in 41 patients at 4 hr and 24 hr after reinjection to determine whether the 4-hr 99mTc scan could replace the 24-hr 111In scan for detecting intraabdominal sepsis. Abdominal infection was confirmed in 12 cases. The 4-hr 99Tc-leukocyte scan, the 4-hr 111In-leukocyte scan, and the 24-hr 111In-leukocyte scan yielded a sensitivity of 100%, 67%, and 100%, respectively, and a specificity of 62%, 90%, and 86%, respectively. The 24-hr 99mTc-leukocyte scan also produced a sensitivity of 100%, but it was falsely positive in all 29 cases without infection due to physiologic bowel uptake. False-positive 4-hr 99mTc-leukocyte scans were also produced by physiologic bowel uptake in seven cases all of whom had true-negative 4-hr and 24-hr 111In-leukocyte scans. Because of the high incidence of false-positive 4-hr [99mTc]HM-PAO leukocyte scans, it was concluded that they could not replace 24-hr 111In-leukocyte scans for detecting intraabdominal sepsis, and that serial 99mTc leukocyte scans starting earlier than 4 hr after reinjection must be evaluated.     

Gallium 67 citrate scanning and serum angiotensin converting enzyme levels in sarcoidosis

Gallium 67 citrate scans and serum angiotensin converting enzyme (ACE) levels were obtained in 54 patients with sarcoidosis and analyzed in relation to clinical manifestations. 67Ga scans were abnormal in 97% of patients with clinically active disease (n = 30) and in 71% of patients with inactive disease (n = 24). Serum ACE levels were abnormally high (2 standard deviations above the control mean) in 73% of patients with clinically active disease and in 54% of patients with inactive disease. Serum ACE levels correlated significantly with 67Ga uptake score (r =.436; p less than .005). The frequency of abnormal 67Ga scans and elevated serum ACE levels suggests that inflammatory activity with little or no clinical expression is common in sarcoidosis. Abnormal 67Ga scans were highly sensitive (97%) but had poor specificity (29%) to clinical disease activity. The accuracy of negative prediction of clinical activity by normal scans (87%) was better than the accuracy of positive prediction of clinical activity by abnormal scans (63%). 67Ga scans can be used to support the clinical identification of inactive sarcoidosis.     

Tumor model studies of 131I-tetracycline and other compounds.

Iodine-131-tetracycline (131I-TET) was prepared by allowing tetracycline hydrochloride to react with radioiodide in acidic methanol (labeling efficiency greater than 85%). This preparation was found to be stable at--4 degrees C for at least 72 hr. Some minimal in vivo breakdown did occur. The 131I-TET, 67Ga, and several 99mTc compounds were studied in a rat hepatoma model. The incorporation of the radiopharmaceuticals into the tumor occurred rapidly, with peak levels at 0.5 and 24 hr after injection for 131I-TET and 67Ga, respectively. The clearnace of the radiopharmaceutical from nonviable tumor was slower than for viable tumor, and by 72 hr after injection the greatest concentration of radioactivity appeared in the nonviable fraction. All normal tissues showed faster clearance than did tumor tissue, regardless of viability. Decreasing the quantity of 131I-TET injected increased the percent of uptake in the nonviable tumor tissue but had no effect on the viable tumor uptake. Of the 99mTc compounds studied, the phosphates developed the highest tumor-to-background ratios. Unfortunately these ratios were not as high as those achieved for 67Ga or 131I-TET.     

Gallium-67-citrate scanning in primary cancer of the liver: diagnostic value in the presence of cirrhosis and relation to alpha-fetoprotein.

Gallium-67-citrate and 99mTc-sulfur colloid scans were performed in 38 South African blacks with primary hepatocellular cancer. Selective uptake of the radinuclide by the tumor occurred in 27 patients (70%). In 12 out of 18 patients with associated cirrhosis, 67Ga was concentrated in the defect or defects visible on the 99mTc-sulfur colloid scan, but in the remaining 6 cases (33%), the 2 scans were identical and the defects may have been attributed wrongly to cirrhosis. Alpha-fetoprotein (AFP) was detected by immunodiffusion in the serum of 26 patients. Twenty-one of these showed selective uptake of 67Ga by the tumor as compared with 6 out of 12 patients in whom this protein could not be detected. We were therefore unable to confirm a previous finding of a greater uptake of the of the radionuclide in AFP-negative primary liver cancer.     

Trial manufacture of a plunger to reduce finger exposure

According to the results of to a survey conducted by the Japanese Society of Nuclear Medicine Technology in 1995, the mean monthly exposure dose to the trunk of nuclear medicine technicians was less than 0.2 mSv at more than 75% of the institutions, whereas the exposure dose to the fingers exceeded 0.5 mSv at 30% of the institutions. Many recent radiopharmaceuticals are being supplied as the syringe type, and while the syringe is surrounded by a tungsten or lead-glass shield, there is no shielding of the syringe needle or the plungers. The plastic plunger provides little shielding effect, and even when a tungsten plunger is used, calculating back from the leakage rate, the shielding effect for 99mTc is approximately 75%. We therefore trial-manufactured a plunger devised in such a manner as to considerably reduce exposure of the fingers and evaluated its shielding effect from leakage rate obtained with a dual-detector scintillation camera when the radionuclides 99mTc, 67Ga, 201Tl, and 123I were used. Its performance was satisfactory, with shielding effects (99mTc, 99%; 67Ga, 95%, 201Tl, 95%; 123I, 73%) about the same or better than back-calculated from the leakage rates.     

Evaluation of 67Ga accumulation around the shoulder joint--comparison with 99mTc-MDP

67Ga scintigraphy was performed in 865 patients, and in 1078 examinations. 67Ga accumulation was evaluated retrospectively for asymmetric accumulation in the shoulders. Approximately 50% of patients showed no asymmetric distribution of 67Ga in the shoulders. About 40% of patients showed increased accumulation in the right side and about 10% of patients showed increased accumulation in the left side. A change of 67Ga distribution in the shoulder joints was recognized in about 30% of patients during the follow-up study. Reasons for asymmetric distribution of 67Ga in the shoulders were considered to be due to bone metastasis, changes of local blood flow, edema, irradiation, muscle atrophy after cerebral paralysis, and operation. 67Ga scintigraphy showed a broader range and more prominent accumulation in the soft tissues around the shoulder joint than 99mTc-MDP scintigraphy. The accumulation of 99mTc-MDP was recognized to be in the center of the region of 67Ga accumulation. 99mTc-MDP scintigraphy showed more prominently increased accumulation than 67Ga scintigraphy in patients with osseous lesions. Similar factors appeared to have had an influence on the abnormal accumulation of 67Ga and 99mTc-MDP around the shoulder joint.     

Comparison of 99Tcm-HMPAO-labelled white blood cells and 67Ga citrate scans to detect myocarditis in the acute phase of Kawasaki disease.

Myocardial imaging with 99Tcm-HMPAO-labelled white blood cells (WBC) and 67Ga citrate was used to detect myocarditis in the acute phase of Kawasaki disease among 22 infants and children; 18 cases of myocarditis were detected by 99Tcm-HMPAO-labelled WBC heart scans, but only one case was detected by 67Ga citrate heart scans. In conclusion, 99Tcm-HMPAO-labelled WBC scanning provides a more sensitive method than 67Ga citrate scanning in the detection of myocarditis in Kawasaki disease.     

Synthesis, tissue distribution and tumor uptake of 99mTc- and 67Ga-tetrasulfophthalocyanine

Complexes of tetrasulfophthalocyanine with 99mTc, 69Ga and 67Ga were prepared by the condensation of sulfophthalic acid with the appropriate metal-species. The Ga-complex was also obtained by exchange of the central hydrogens of the empty tetrasulfophthalocyanine. The labeled complexes were purified by thin layer chromatography and characterized by their chromatographic properties. Their biodistribution in rabbits and tumor-bearing rats revealed that most of the radioactivity accumulated in the kidneys, liver, ovaries, adrenals and spleen. Comparison of these distribution pattern with those of [99mTc]pertechnetate and 67Ga-citrate confirmed the in vivo stability of the labeled complexes. The 67Ga-complex reached better tumor-to-blood and tumor-to-muscle ratios than 67Ga-citrate.