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Biomedical subjects

G M Kolodny

Publications and source records attributed to G M Kolodny.

At least 19 recordsLinked to original sources

Lymphoma: predictive value of Ga-67 scintigraphy after treatment.

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.

Adolescent

Local and systemic effects of radiation on bone metabolism measured by quantitative SPECT.

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.

Bone and Bones

Stress fractures associated with osteosarcoma of the lower limb.

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.

Adult

In vivo measurements of the fraction of dose of bleomycin labeled with cobalt 57 delivered to human tumors.

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.

Adolescent

Natural evolution of cardiac function, cardiac pathology and antimyosin scan in a murine myocarditis model.

Serial technetium-99m radionuclide ventriculograms, indium-111 antimyosin antibody scans and tissue biodistribution studies were performed in C3H/He mice with experimentally induced viral encephalomyocarditis and the results were compared with pathologic assessments of myocardial necrosis. Postinfection ejection fraction decreased on days 10 (20.7 +/- 5.5%, n = 6), 20 (18.6 +/- 15.2%, n = 5), 30 (18.5 +/- 7.7%, n = 5) and 150 (30.0 +/- 18.7, n = 6) (p less than 0.001) in comparison with that in uninfected control mice (63.3 +/- 3.1%, n = 6). In the same group of animals, indium-111 antimyosin antibody scans showed intense positive myocardial accumulation on day 10 (in six of six mice) and only slight accumulation on day 20 (in one of five mice). In the chronic stage, two of five mice on day 30 and two of six mice on day 150 still showed positive uptake. The antimyosin scan myocardium to lung uptake ratio (expressed as mean count density [mean counts/pixel of the region] ratio) increased greatly on day 10 (p less than 0.001 versus values in uninfected control mice) but not subsequently. Biodistribution studies of the indium-111 antimyosin antibody showed that the heart to blood count ratio was significantly higher on day 10 (p less than 0.001 versus values in control mice) but not on days 20, 30 and 150. Pathologic examination showed active and ongoing severe myocardial necrosis with dilated ventricles on day 10. On day 20, there was less active necrosis and healing had appeared to begin. On days 30 and 150, myocardial fibrosis increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

In vivo SPECT quantitation of bone metabolism in hyperparathyroidism and thyrotoxicosis.

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.

Adult

Three years' experience with an all-digital nuclear medicine department.

We describe our all-digital, filmless, department of nuclear medicine, which has been fully operational for 3 years. The approach to the design and implementation of a nuclear medicine picture archiving and communication system (PACS) is discussed, as well as enhancements found to be necessary or desirable during our 3 years of experience using the system. Studies are initially viewed on remote monitors in the reading room, and transferred from multiple vendor's computers to the PACS by floppy disc network. Scans are analyzed on networked image workstations using a variety of software imaging tools. Reports are dictated into a digital voice storage system, allowing the referring physician immediate telephone access. The dictated report is typed into a computer, electronically edited, reviewed, billed, and printed for appropriate distribution on an integrated medical information system. The final report is stored on the PACS, along with the scan image and other patient information on 1-gigabyte removable optical discs. Two networked optical disc drives allow us to have approximately 3 years of our department's studies available instantly, allowing recall of previous studies for comparison with the current scan. Emergency night and weekend studies are sent via modern over normal phone lines to the on-call physician, who has a similar image workstation at home. Digital image storage allows for easy manipulation of the data, such as gray scale manipulation and cine (movie) display. Cost analysis shows significant savings compared with a film-based department. We conclude that an all-digital nuclear medicine department is practical, cost effective, and beneficial to both patients and staff.

Analog-Digital Conversion

Normal and abnormal Ga-67 SPECT anatomy in patients with lymphoma.

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.

Gallium Radioisotopes

Ga-67 SPECT before and after treatment of lymphoma.

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.

Adolescent

Administered dose and tumor dose of bleomycin labeled with cobalt-57 in mice and men.

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.

Aged

SPECT quantitation of iodine-131 concentration in phantoms and human tumors.

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.

3-Iodobenzylguanidine

The concentration of bleomycin labeled with Co-57 in primary and metastatic tumors.

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.

Adolescent

A practical SPECT technique for quantitation of drug delivery to human tumors and organ absorbed radiation dose.

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.

Contrast Media

Evaluation of routine telephone transmission of nuclear medicine studies.

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.

Computer Communication Networks

Quantitative bone scintigraphy using SPECT.

A quantitative single photon emission computed tomography (SPECT) technique for measuring radiopharmaceutical uptake in humans has been applied to bone scintigraphy. The method was validated by comparing SPECT measured percent of injected [99mTc]MDP in 16 normal skulls with well counter measurements of samples of the same bones obtained at surgery. A very good correlation (r = 0.96) was found. A very good interobserver correlation (r = 0.99) and agreement were also obtained when using quantitative bone scintigraphy (QBS). Control SPECT studies of uptake in the right and left iliac bones and the right and left sacroiliac regions in each patient showed no significant differences between the contralateral sides. Studies done in seven subjects at 2 and 4 hr after the same injection and in nine subjects 4 to 8 mo later in the same subjects showed a very good agreement and no significant differences between the two measurements were found. QBS is suggested as an accurate and reproducible index for assessment of the mass of remodeling bone. Preliminary results showed differences in QBS of normal subjects at different ages. A group of 68 young patients aged 18-26 yr showed a significant higher QBS (p less than 0.001) when compared to an older group of 62 patients aged 50-85 yr. There was, however, a wide range of uptake values for the same bone in the same group, suggesting that the method should best be used for following individual patients over time.

Adult

Gallium 67 imaging in monitoring lymphoma response to treatment.

The value of gallium 67 (Ga) imaging in monitoring lymphoma response to treatment was assessed in 25 patients with Ga-avid tumors and compared to body computed tomography (CT), chest radiographs, and palpation of tumor infiltrated peripheral lymph nodes. Ga imaging was negative in 95% (20/21) of the patients who were clinically considered to be in remission and in whom treatment was stopped. The disease did not recur during a follow-up of 12 to 26 months in 15 patients. Six patients developed recurrence of the disease 3 to 12 months after treatment was stopped. In all six patients Ga imaging became positive again at the time of the appearance of active disease. In the group of patients in remission, CT was negative in 57% (11/19), chest x-rays in 55% (6/11) and peripheral lymph nodes were palpated in none of the patients (13/13). In four patients that did not achieve remission after treatment, Ga scans were positive. Ga imaging appears useful in monitoring lymphoma response to treatment. This is probably because Ga imaging monitors tumor cell viability, whereas body CT and chest radiographs show the tumor mass, which may consist of fibrotic or necrotic tissue.

Adolescent

Focal lung uptake of gallium-67 in patients with acquired immunodeficiency syndrome secondary to pneumocystis carinii pneumonia.

It is generally accepted that the lung uptake of 67Ga in patients with pneumocystis carinii pneumonia (PCP) is diffuse and bilateral. Three cases of focal lung uptake of 67Ga in AIDS patients with PCP but without other opportunistic infection are described. While focal lung uptake is characteristic of opportunistic infections other than PCP, we wish to emphasize that focal uptake of gallium in the chest does not rule out PCP and may represent its earliest stage of presentation.

Acquired Immunodeficiency Syndrome