Biomedical subjects
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The authors describe a patient with myelofibrosis who showed intense Ga-67 uptake in spite of being severely leukopenic and receiving large amounts of antibiotics. They conclude that false-negative results associated with leukopenia or intensive antibiotic treatment may not always be correct.
Two hundred and twenty five liver hemangiomas in 166 patients were studied with Tc-99m labeled RBC and are the basis for this atlas. All hemangiomas showed various presentations of the perfusion blood pool mismatch, which is the basis for diagnosis. The size of the hemangiomas was the factor that determined the mixing of the Tc-99m RBC with the blood and, hence, the sequence of visualization of the lesion. Hemangiomas may appear as multiple lesions on liver scan and imitate metastases. Ninety-five hemangiomas appeared in 36 patients as multiple focal abnormalities. Hemangiomas are extremely variable in size. They may be huge (31 hemangiomas) and sometimes occupy most of the abdomen. Or they can be very small and are then detected only by SPECT (two cases). Thrombosed large hemangiomas appear as focal defects on Tc-99m RBC.
The negative predictive value (PV-) and positive predictive value (PV+) of gallium-67 scintigraphy and computed tomography (CT) were compared after treatment in 43 patients with Hodgkin disease and in 56 patients with non-Hodgkin lymphoma. The usefulness of these studies in predicting survival was also evaluated. In patients with Hodgkin disease, the PV- of Ga-67 scintigraphy was 0.84 and of CT was 0.88. The PV+ was 0.80 for Ga-67 studies and only 0.29 for CT. In patients with non-Hodgkin lymphoma, the PV- of Ga-67 scintigraphy was 0.84 and of CT was 0.80. The PV+ was 0.73 and 0.35, respectively. For both groups, the differences in disease-free survival between patients with negative and positive Ga-67 studies were significant (P less than .05 in Hodgkin disease and P less than .001 in non-Hodgkin lymphoma), but the differences were not significant for CT. These data show that, after treatment of patients with lymphoma, Ga-67 scintigraphy is a good predictor of clinical outcome and can be used beneficially in patient treatment.
Quantitative bone scintigraphy (QBS), which measures 99mTc-MDP uptake expressed as percent of injected dose per cc, indicates bone metabolism. It is measured in the bones of patients before and after radiation treatment and then compared to normal controls. QBS was performed in a group of 22 normal individuals and was measured twice, 2-10 mo (mean 4.9) apart. There was no significant difference between the two measurements. QBS was performed also in 28 patients before, immediately after and at certain time intervals after radiation therapy for cancer. Both the irradiated and the nonirradiated bones showed significant decreases in bone metabolism at 2-18 mo (mean 8.8) after irradiation. In addition, increases and decreases of 99mTc-MDP uptake were similar in the irradiated and in the nonirradiated bones, and there were significant correlations of the QBS values in the different bones of each individual patient. The etiology of the changes in bone metabolism in the nonirradiated bones is not yet fully understood, but it appears to be the result of a systemic effect of radiation.
Three patients with osteosarcoma of the femur developed abnormal radiopharmaceutical uptake in the bones of the contralateral leg. This uptake was not due to metastases. The histology in one patient, the form of the lesion and the disappearance of the abnormal uptake without treatment in the other two, indicated that the uptake was probably due to stress fractures. Changes in weight bearing and walking in the normal leg as a result of the osteosarcoma in the other leg could have been the cause of the stress fractures. It should be recognized that new abnormal uptake on bone scintigraphy in patients with osteosarcoma of the leg may not necessarily indicate metastasis. It may be caused by a stress fracture and disappears after rest.
Concentrations of bleomycin labeled with cobalt 57 (Co-bleo) over time were measured in vivo in 17 patients with 32 sites of lymphoma and 18 patients with lung tumors after administration of the same dose of bleomycin. There were marked variations in individual tumor drug concentrations even among tumors with the same histologic type, indicating that the tumor concentration of this drug in individuals cannot be predicted from the administered dose. Also, tumor concentration could not be predicted from the area under the concentration over time curve (AUC) of Co-bleo in the blood; there was no correlation (r = 0.53) between the AUC and the concentration in the tumor at any point in time between 30 minutes and 8 hours after injection. There was no significant difference in the percent of the injected dose per milliliter (%ID/ml) which was delivered to the tumor when low and high amounts of bleomycin were administered to the same patient. Also, a good correlation (r = 0.88) between the %ID/ml over time was found when injection of low and high doses of bleomycin were compared. The results indicate that using quantitative single photon emission computed tomography (SPECT) and a labeled tracer dose it is possible to predict what fraction of the dose of a chemotherapeutic drug will concentrate in an individual patient's tumor in vivo. They also show that, for bleomycin, escalation of dose will result in a proportional increase of tumor concentration. This increase depends on individual properties of tumors which can be measured quantitatively in vivo by SPECT and are expressed as percent of %ID/ml of tumor tissue.
Extracorporeal shock-wave lithotripsy has altered the therapeutic approach to urinary stone disease. Recently, a method was developed in which shock-wave generation is obtained piezoelectrically. To evaluate the effect of extracorporeal piezoelectric lithotripsy (EPL) on renal function, 20 patients were studied prior to and after EPL of renal calculi. Renal cortical function was evaluated by using a previously described and validated quantitative single photon emission computerized tomography (SPECT) method to measure individual absolute uptake of technetium-99m dimercaptosuccinic acid (Tc-99m-DMSA). Twenty kidneys were treated, and the 19 contralateral kidneys were without stone disease (1 patient had a single kidney). The absolute kidney uptake of Tc-DMSA in the normal kidneys was 21.4% +/- 6.2% before and 22.2% +/- 6.4% after EPL. For the treated kidneys the absolute update was 16.8% +/- 5.3% and 16.8% +/- 4.7% before and after, respectively. There was no statistical significant difference between pre- and post-treatment values. The absolute kidney uptake was significantly lower (p less than 0.01) in the treated than in the normal kidneys. This study indicates that the EPL procedure did not cause any damage to cortical function detectable by the DMSA uptake.
The ability to evaluate kidney function in each kidney separately by quantitative SPECT was tested in 20 patients with a single kidney and varying degrees of renal disease. Technetium-99m-dimercaptosuccinic acid (99mTc-DMSA) uptake was compared with renal function measured by creatinine clearance and serum creatinine. There was a good correlation for both serum creatinine (r = 0.89, y = 24.6 *X -1.15, error = 5.6, p less than 0.001) and creatinine clearance (r = 0.76, y = 0.6 *X 0.84, error = 8.0, p less than 0.001). The results indicate that SPECT quantitation of 99mTc-DMSA uptake can be used as an indicator of the function of each kidney individually.
Bone metabolism was assessed in vivo and noninvasively using quantitative SPECT. The effect of endocrine abnormalities on bone metabolism was studied in 27 patients with primary hyperparathyroidism (HPT) and 12 patients with thyrotoxicosis (TTX). Quantitative bone scintigraphy (QBS) values of 99mTc-MDP uptake were compared to normal values matched for sex and age. Bones with significantly increased QBS values indicating increased bone metabolism were identified in the two patient groups. Fifty-one percent of the bones in patients with HPT and 78% in patients with TTX showed significantly increased QBS values. Increase in bone metabolism was highest in the femoral shaft. Seven patients with HPT and five with TTX were successfully treated. Six patients with HPT and four patients with TTX showed significant decrease of bone metabolism with normal QBS values after three months. The results indicate that QBS can be used to evaluate bone metabolism and its response to treatment in individual bones in patients with endocrine abnormalities.
The appearance of normal Ga-67 SPECT images in the coronal, sagittal and transaxial planes is described. The normal tomographic appearance of bone, liver, spleen, and gut is shown and compared with disease involvement above and below the diaphragm.
The results of planar and single photon emission computed tomography (SPECT) gallium-67 scintigraphy performed before and after treatment were compared in 77 patients with lymphoma at 240 sites. Before treatment, the sensitivity of planar scintigraphy was 78% and the specificity was 97%; after treatment, 84% and 96%, respectively. Before treatment, SPECT had a sensitivity of 85% and a specificity of 98%; after treatment, 92% and 99%, respectively. In addition, SPECT allowed better anatomical localization and showed the entire extent of lesions at 36 sites. SPECT was of special value after treatment in excluding disease at 16 sites with residual masses seen at computed tomography (CT). Long-term follow-up in these patients showed that their condition was in complete remission and that the CT appearance of a residual mass does not always mean residual cancer. Thus, Ga-67 SPECT is a suitable imaging technique for monitoring the response of lymphoma to treatment.
Tumor concentrations of the chemotherapeutic drug, bleomycin, labeled with cobalt-57 (Co-bleo) were compared in mouse tumor models and in human lung tumors using quantitative single-photon emission computed tomography. Drug concentrations in histologically similar human tumors showed marked variability for the same injected dose (ID). Small cell carcinomas showed concentrations between 1.09 and 8.85 %ID/cc x 10(-3) while non-small cell lung tumors showed a concentration variation between 0.36 and 6.75 %ID/cc x 10(-3). In contrast to the situation in human tumors, uptake in mouse tumors showed only slight variability in animals with the same tumor model. EMT-6 tumors in mice showed at 6 hr significantly higher uptake of Co-bleo (p less than 0.001) and significantly higher tumor-to-lung ratio (p less than 0.001) when compared to murine fibrosarcomas. The EMT-6 tumors in contrast to the fibrosarcomas responded to bleomycin treatment in a dose dependent manner. The results indicate that while in mice the tumor dose closely follows the administered dose, in humans, the tumor dose and the tumor-to-lung ratio in the individual patient cannot be predicted from the administered dose.
The validity of SPECT measurement of iodine-131 (131I) concentration was tested in vitro in phantoms and in vivo by measuring bladder urine concentrations. Phantom studies comparing known and SPECT measured concentrations showed a good correlation for 131I (r = 0.98, s.e.e. = 20.94 counts/voxel) for phantoms of 25 to 127 cc and concentrations of 0.13 to 9.5 microCi/cc. The in vivo, in vitro correlation of 131I concentrations in the urine was also good (r = 0.98, s.e.e. = 0.677 microCi/cc). Quantitative SPECT was used to calculate the effective half-life and dosimetry of radioiodine in 12 sites of thyroid carcinoma in seven patients. SPECT was also used to determine the dosimetry of [131I]MIBG (metaiodobenzylguanidine) in two patients with carcinoid, two with neuroblastoma, and one with pheochromocytoma. The radiation dose for thyroid carcinoma metastases varied between 6.3 and 276.9 rad/mCi. The dose from MIBG varied between 13.4 and 57.8 rad/mCi. These results indicate the validity of quantitative SPECT for in vivo measurement of 131I and the need to measure the concentration of 131I in individual human tumor sites.
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Two patients with treated lymphoma demonstrated a residual mass on CT following treatment. In both cases gallium-67 (67Ga) scintigraphy demonstrated increased uptake in the original tumor mass and no uptake in the mass after treatment. In both cases the entire residual tumor mass was resected and found to contain no cancer tissue. This is further evidence of the role 67Ga scintigraphy may play in monitoring response of lymphoma patients to treatment. In contrast, other imaging modalities such as ultrasound, plain film x-rays, or CT only show the presence of a mass but not its nature.
The concentration over time of bleomycin labeled with Co-57 was measured in 39 primary and metastatic tumor sites in 16 patients using a newly developed and validated single photon emission computed tomography (SPECT) method. There were nine primary tumors, 15 metastatic tumors, and five multifocal lymphomas. Co-bleomycin concentrations also were measured in primary and metastatic B-16 melanoma tumors in mice. In humans, metastases to lymph nodes (1.58 +/- 0.51 %ID/ml X minutes) showed significantly higher (P less than 0.01) tumor cumulative concentrations of Co-bleomycin than metastases to liver, bone, lung, and brain (0.76 +/- 0.20 %ID/ml X minutes). The cumulative concentrations of Co-bleomycin in human lymphomas (1.1 +/- 0.25 %ID/ml X minutes) also were significantly higher (P less than 0.01) than the concentrations in human metastases other than lymph nodes. The cumulative concentration in cerebral metastases (0.65 +/- 0.18 %ID/ml X minutes) was significantly lower (P less than 0.05) than in noncerebral metastases (1.22 +/- 0.53 %ID/ml X minutes). Primary tumors in humans showed higher concentrations of Co-bleomycin than metastases, except for lymph nodes. In contrast with humans, murine metastases showed higher concentrations of Co-bleomycin (6.20 +/- 2.65 %ID/g) than primary tumors (2.94 +/- 0.90 %ID/g) (P less than 0.001). The concentrations of Co-bleomycin in murine tumors that were affected by bleomycin were about three orders of magnitude higher than in human tumors. The results of this in vivo study document the differences in drug delivery of Co-57-labeled bleomycin to human primary and metastatic tumors and show differences in drug delivery between human and murine tumors.
A practical quantitative single photon emission computed tomographic (SPECT) technique based on an empirical threshold analysis permits accurate measurements in humans of drug delivery and absorbed radiation dose. The limits of the method have been explored using a wide range of phantom volumes, concentrations, and target-to-nontarget ratios. A threshold of 43% was found to give the best results using volumes of 30 to 3,800 cc. An excellent correlation (r = .99 with a standard error of estimate [SEE] of 41 cc) was found between SPECT measured volumes and actual phantom volumes. A similarly high correlation (r = .98, SEE = 260 counts/voxel) was found in 77 measurements of concentrations between 0.01 and 3.6 microCi/cc. There was a direct relationship between the target-to-nontarget ratio of phantoms and the accuracy of volume measurements. The technique has been validated by an excellent in vivo/in vitro correlation of uptake in human tumors. The tumor cumulative concentration and tumor-to-blood ratio were used for assessment of drug delivery. In vivo quantitative measurements of the pharmacokinetics of technetium-99m (99mTc) glucoheptonate, cobalt-57 (57Co) bleomycin and platinum-195m (195mPt) cisplatin in human tumors in vivo indicates that, in contrast with tumor models in animals, there is a marked variability in drug delivery even in tumors with the same histology. Future development of labeled drugs should make it possible to use quantitative SPECT for predicting tumor response to therapy and for tailoring chemotherapy for the individual patient under treatment. SPECT quantitation of organ concentration was used for Medical Internal Radiation Dose committee (MIRD) calculations of organ absorbed radiation dose from 99mTc-labeled RBCs. Excellent in vivo/in vitro correlations were obtained between SPECT measured concentrations of blood radioactivity in the heart and in vitro measurements of blood samples. The possibilities and limitations of this technique are discussed and its use for in vivo measurement in humans of absorbed radiation dose from radiopharmaceuticals is suggested.
Rapid and reliable transmission of nuclear medicine studies using conventional telephone lines and commercially available modems and computer systems has been accomplished through use of software developed within the authors' hospital. Original digital images of all-night and weekend studies, acquired on any of the acquisition computers from different manufacturers, are now routinely sent for remote reading at the physician's home. Data, software, and letters are routinely exchanged using modems and standard telephone lines with a sister institution in Haifa, Israel. The software has been designed to achieve no loss data compression and minimal turnaround time loss. Thus, an average lung perfusion image or gallbladder study requires about 1-3 minutes of transmission time. Full analysis and display software is available on the remote computer.