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PubMedDate not supplied

Phase I trial of technetium [Leu13] bombesin as cancer seeking agent: possible scintigraphic guide for surgery?

AIMS AND BACKGROUND: Bombesin-like neuropeptides work as neurotransmitters and growth factors at the same time. Several human cancers show overexpression of three receptors for mammalian counterparts of amphibia bombesins (ABNs), ie gastrin-releasing peptide (GRP), neuromedin B (NMB) and possibly another peptide. ABNs in turn are able to bind to mammalian and human receptors in vitro, and it is therefore interesting to study radioisotope-labeled bombesin (BN) and BN-like peptides as cancer seeking agents. METHODS AND STUDY DESIGN: Starting from the amino acid sequence of [Leu13] ABN, the Demokritos Institute has synthesized and labeled with technetium a new BN-like peptide that has the same biological characteristics as the amphibian peptide; changes were made only in the N-terminal part of the tetradecapeptide. After having obtained satisfactory results with 99mTc BN in a preclinical study, we started a phase I trial involving cancer patients as well as normal volunteers in Tomsk. Three normal volunteers, one patient with small cell lung cancer and one patient with primary prostate cancer were studied after iv injection of 185 MBq, corresponding to 0.7 micrograms of 99mTc BN. Dynamic images of the tumors were acquired for 20 mins, followed by SPET. Total body images were acquired in patients and normal volunteers 1 and 3 h after 99mTc BN acquisition. In addition, 99mTc sestamibi scintigraphy was performed in the patient with small cell lung carcinoma. RESULTS: No relevant side effects were observed. Both tumors were well visualized on early 1-2 mins images with planar as well as tomographic imaging. Total body images showed radioactivity in the liver, kidneys and thyroid gland. The stomach and spleen were ever imaged. Radioactivity was found in the urinary bladder 4 mins after injection in the patient with prostate cancer. Three-hour total body scans showed radioactivity in the duodenum. In the patient in whom also 99mTc sestamibi scintigraphy was performed, thyroid uptake was much higher with sestamibi than with 99mTc BN, whereas the uptake of small cell lung carcinoma was higher with 99mTc BN than with sestamibi. CONCLUSIONS: 99mTc BN is able to clearly image tumors with BN receptor overexpression. Our first impression is that in the future this radiopharmaceutical may serve as a cancer seeking agent and, due to its high tumoral uptake, also as a radiotracer for radioisotope-guided surgery.

Bombesin↗
PubMed1982

Technetium-99m pyrophosphate uptake in spontaneously occurring perimyocardial lesions in an inbred strain of DBA/2 mice.

The spontaneous occurrence of perimyocardial calcification localized in the right ventricle has been reported in an inbred strain of DBA/2 mice. In this paper we examined the correlation between the myocardial uptake ratio of technetium-99m pyrophosphate (99mTc-PYP) and pathological findings in these mice ranging in age from one to 12 months and became lower with age, while calcification and fibrosis in the perimyocardium of the right ventricle became more prominent in aged mice. This may be due to an insidious onset of degeneration with calcification and fibrosis in spontaneously occurring perimyocardial lesions in these mice. Persistent abnormal uptake of 99mTc-PYP observed in the present study suggests the usefulness of such scintigrams in the diagnosis of chronic perimyocardial disease.

Animals↗
PubMed1987

Prognostic value and limitation of doughnut pattern of technetium-99m pyrophosphate myocardial uptake in acute anterior infarction.

The prognostic significance of the doughnut pattern of technetium-99m pyrophosphate myocardial uptake was evaluated in 140 patients with acute anterior infarction. There were significantly higher early complications, greater mortality and more severe hemodynamic abnormalities in the doughnut pattern group than in the non-doughnut pattern group. The former had a more depressed left ventricular ejection fraction and larger thallium-201 defect size (27.6 +/- 10.4 versus 40.0 +/- 13.5%, p less than 0.001 and 9.9 +/- 3.6 versus 5.6 +/- 3.3, p less than 0.001, respectively). There was, however, considerable overlap of the ranges of these variables for both groups. The patency rate of the infarct vessel during the acute phase of infarct in each group was similar (54.8 versus 45.2%). It is concluded that the prognostic value of the doughnut pattern may be limited to some extent by this overlapping and the presence of this pattern does not appear to correlate with the lack of residual blood flow to the infarcted area.

Cardiac Catheterization↗
PubMed1988

Technetium 99m HMPAO scanning in patients with subarachnoid haemorrhage: a preliminary study.

Technetium 99m hexamethylpropylene amine oxime (HMPAO) is an agent which, when injected intravenously, gives images which reflect cerebral blood flow. Seven patients who had suffered subarachnoid haemorrhage were examined by cerebral angiography and by 99Tcm HMPAO scanning. The two studies were compared and in six cases there was evidence of decreased cerebral perfusion in relation to the ruptured aneurysm causing the subarachnoid haemorrhage. In one case no cause for the haemorrhage was demonstrated angiographically, and the HMPAO study was normal. In two of the six cases, spasm of the cerebral artery distal to the ruptured aneurysm was seen angiographically and it appears that 99Tcm HMPAO scanning does not correlate with gross arterial spasm but reflects smaller degrees of cerebral underperfusion not demonstrable by angiography. The results demonstrate a relationship between local decreased cerebral perfusion and ruptured cerebral aneurysm and may be of use in determining which aneurysm has bled in patients who have more than one aneurysm demonstrated angiographically.

Female↗
PubMed1988

Technetium-99m HMPAO imaging in patients with basal ganglia disease.

Technetium 99m hexamethylpropylene-amine oxime (HMPAO) is trapped by cerebral grey matter and the basal ganglia on its first pass through the brain. To assess its potential for studying patients with diseases of the basal ganglia, a study of 15 normal volunteers and 32 patients with known or suspected basal ganglia disease have been investigated. Sixteen patients with idiopathic Parkinson's disease showed no abnormality of the basal ganglia and varying degrees of cerebral underperfusion consistent with their intellectual status. Eight patients with Huntington's chorea showed a characteristic pattern of reduced or absent caudate nucleus uptake. Patients with diseases affecting the basal ganglia, such as Fahr's disease, Wilson's disease and hemibalismus had varying degrees of basal ganglia underperfusion as demonstrated by an HMPAO scan. We believe that this new radiopharmaceutical for the demonstration of cerebral blood flow shows significant potential for the diagnosis and management of patients with basal ganglia disease.

Adult↗
PubMed1989

The localization of myocardial ischaemia with technetium-99m methoxy isobutyl isonitrile and single photon emission computed tomography.

Thirty-two patients with suspected coronary artery disease were studied by single photon emission computed tomography (SPECT) imaging with oblique reconstructions of the myocardium following the intravenous administration of technetium-99m methoxy isobutyl isonitrile at peak exercise. All patients also underwent three-vessel coronary angiography. The SPECT technique produced very detailed images allowing easy delineation of localized myocardial defects. Segmental myocardial uptake defects were compared with diseased vessels as shown at angiography. A good correlation was shown between right coronary artery (RCA) disease and mid and proximal inferior segments and between left circumflex (LCx) artery disease and mid and proximal lateral segments, allowing accurate localization of a defect to one of these two vessels' territories. Sensitivity and specificity of detection of disease of the RCA and LCx artery were high. Defects associated with a lesion of the left anterior descending vessel were more variable.

Adult↗
PubMed1983

Radionuclide imaging in myocardial sarcoidosis. Demonstration of myocardial uptake of technetium pyrophosphate99m and gallium.

A patient had severe congestive cardiomyopathy secondary to myocardial sarcoidosis. The clinical diagnosis was confirmed by radionuclide ventriculography, thallium 201 (201Tl), gallium-67 (67Ga), and technetium-99m (99mTc) pyrophosphate (TcPYP) scintigraphy. Myocardial TcPYP uptake has not been reported previously in sarcoidosis. In this patient, TcPYP was as useful as gallium scanning and thallium imaging in documenting the myocardial process.

Adult↗
PubMed1999

Perioperative hepatic functional risk assessed with technetium-99m diethylenetriamine pentaacetic acid-galactosyl human serum albumin liver scintigraphy in patients undergoing pancreaticoduodenectomy complicated by obstructive jaundice.

CONCLUSION: Liver scintigraphy with technetium-99m diethylenetriamine pentaacetic acid-galactosyl human serum albumin (Tc-GSA) can be used to predict outcome of biliary drainage and hepatic function after pancreaticoduodenectomy in patients with pancreatic, biliary, and ampullary carcinomas complicated by obstructive jaundice. BACKGROUND: Preoperative obstructive jaundice has been reported as a crucial risk factor for serious postoperative complications in patients undergoing pancreaticoduodenectomy. The aim of the present study was to investigate whether Tc-GSA liver scintigraphy can assess hepatic functional risk in patients with pancreatic, biliary, and ampullary carcinomas complicated by obstructive jaundice. METHODS: Liver scintigraphy was performed before biliary drainage in 18 patients with obstructive jaundice. The maximum removal rate of Tc-GSA (GSA-Rmax; standard normal value > or = 0.60) was calculated. These patients underwent pancreaticoduodenectomy with wide lymphadenectomy. The efficacy of preoperative biliary drainage was assessed with the decrease in serum bilirubin concentration in the first week after biliary drainage. Postoperative liver function was assessed with the increase in serum bilirubin concentration, which was the difference between the immediate preoperative and maximal postoperative bilirubin concentrations. RESULTS: Serum bilirubin decreased more in the first week after biliary drainage in patients with GSA-Rmax > or = 0.60 (7.64 +/- 1.09 mg/Dl/wk) than in patients with GSA-Rmax < 0.60 (3.56 +/- 1.25 mg/DL/wk, p = 0.042). Postoperative bilirubin increased less in patients with GSA-Rmax > or = 0.60 (0.81 +/- 0.30 mg/dL) than in patients with GSA-Rmax < 0.60 (4.00 +/- 0.69 mg/DL, p = 0.0012). Multivariate analysis showed that GSA-Rmax significantly predicted the postoperative bilirubin increase (p = 0.020).

Adult↗
PubMed1986

Technetium-99m pyrophosphate imaging in acute renal failure associated with nontraumatic rhabdomyolysis.

Technetium-99m pyrophosphate (Tc-PYP) imaging was performed in five patients with acute renal failure associated with nontraumatic rhabdomyolysis. Four patients had phencyclidine intoxication and one had viral pneumonia. During the acute phase, marked uptake of pyrophosphate was seen in all patients in several muscle groups, but always in the thigh adductors. The results show that phencyclidine intoxication can result in diffuse muscle uptake of Tc-PYP without overt evidence of muscle injury. Tc-PYP imaging may provide a clue to the cause of acute renal failure in patients with suspected rhabdomyolysis in whom elevations of serum creatine phosphokinase concentrations are equivocal.

Acute Kidney Injury↗
PubMed1982

Bone formation of transplanted autologous bone matrix in rabbit evaluated by technetium radionuclide bone imaging.

In adult rabbits a 12 mm piece of the radius was bilaterally resected and subsequently decalcified. One piece was placed in one of the radial defects and the other in a skin tube on the back. The other radial defect served as a control. The bone formation process was evaluated by roentgenographic examination and quantified radionuclide bone imaging by technetium diphosphonate scintigraphy at 3 and 6 months postoperatively. Reliability of the scintigraphy method was assessed by means of testing interexamination variability where the same sample was measured twice and where no significant difference was found. In the defect restituted with decalcified bone matrix there was a significantly (p less than 0.01) higher bone formation rate at 3 months postoperatively, with a mean increase of 47% compared to the control side. In the skin tube the implanted matrix showed mineral formation both at 3 and 6 months postoperatively and increased radionuclide uptake compared to the adjacent tissues. Technitium radionuclide imaging was found to be a suitable method for evaluation of the bone formation in these small defects.

Animals↗
PubMedDate not supplied

The effect of DMSA loading on the renal handling of technetium-99m in rats.

The renal handling of technetium-99m dimercaptosuccinic acid (99mTc DMSA) was studied in rats treated with high doses of nonradioactive DMSA to inhibit the renal uptake mechanism(s). A static scan was obtained 1 hour after the intravenous (iv) injection of 99mTc DMSA and the radioactivity in kidneys and bladder was calculated as a percentage of the injected amount. Total glomerular filtration rate (GFR) and effective renal plasma flow were also determined. Preloading with DMSA caused a fall in the renal accumulation of 99mTc DMSA together with a small increase in the amount excreted into the urinary bladder. Despite a stable GFR, the total amount of 99mTc DMSA handled by the kidneys (i.e., renal plus bladder activity) was reduced. These findings are compatible with the hypothesis that peritubular uptake and subsequent intracellular fixation are of importance in the renal accumulation of 99mTc DMSA. On the other hand, the radioactivity excreted into the urine probably stems from non-reabsorbed 99mTc DMSA initially filtered by the glomeruli.

Animals↗
PubMed1982

Evaluation of CSF shunt patency by means of technetium-99m DTPA.

Evaluation of 192 cerebrospinal fluid shunts was performed using 1 mCi of technetium-99m DTPA which was injected into the shunt tubing. This was found to be a safe, simple method of evaluating shunt patency. No complications were noted with this procedure, nor was there any documented case of infection related to the injection of the isotope. The sensitivity of the test for evaluation of patency was 97%, specificity 90%, and accuracy 93%. Various patterns of tracer clearance are noted and discussed. The role on this test as an aid in making management decisions is detailed.

Adolescent↗
PubMedDate not supplied

Perioperative changes in hepatic function as assessed by asialoglycoprotein receptor indices by technetium 99m galactosyl human serum albumin.

BACKGROUND/AIMS: Perioperative changes in intrinsic hepatocyte function and functional volume were investigated. METHODOLOGY: 52 cases of liver cancer, including hepatocellular carcinoma, cholangiocellular carcinoma and metastatic carcinoma were studied. There were diagnoses of liver cirrhosis, liver fibrosis and normal liver in 20, 23 and 9 cases, respectively. Hepatic resection of subsegment, one segment, two segments and three segments were performed in 11, 6, 23 and 4 cases, respectively, while 8 cases were diagnosed as inoperable. Assessments were performed before and 4 weeks after hepatectomy with asialoglycoprotein (ASGP) receptor indices, i.e., technetium-99m-galactosyl human serum albumin (TcGSA) uptake by the liver, TcGSA retention in the blood and functional volume as measured by single emission computed tomography (SPECT) with TcGSA as a probe. RESULTS: The hyperbolic relationship between galactosyl human serum albumin (GSA) uptake by the liver and GSA retention in the blood, both of which were independent of functional volume, shifted to the right after hepatectomy. The number of conventional liver function tests correlating to the GSA uptake increased after hepatectomy. By contrast, none of the pre-operative and post-operative tests were correlated with functional volume. Post-operative decrease in intrinsic hepatocyte function can be minimized by selection of mode of hepatic resection. CONCLUSIONS: These results indicate that GSA uptake by the liver can reveal information regarding intrinsic liver function which deteriorates and becomes a decisive factor after hepatectomy.

Adult↗
PubMedDate not supplied

Hepatic functional reserve in patients with biliary malignancies: an assessment by technetium 99m galactosyl human serum albumin hepatic scintigraphy.

PROBLEM: Technetium 99m galactosyl human serum albumin (99mTc-GSA) is a hepatic scintigraphy agent that binds to the asialoglycoprotein receptors. We evaluated the clinical use of the scintigraphy for the pre-operative assessment of biliary malignancies. PATIENTS AND METHODS: Scintigraphy was performed before operation in 56 patients with biliary malignancies. A hepatic uptake ratio of 99mTc-GSA (LHL15; the count ratio of the liver to the sum of the heart and liver 15 min after injection of 99mTc-GSA) was calculated. RESULTS: LHL15 was significantly associated with bilirubin half-life in patients treated before operation with percutaneous transhepatic biliary drainage (P = 0.007). After operation, 4 of 18 patients with LHL15 < 0.925 died within 30 days. The postoperative mortality was significantly greater in patients with LHL15 < 0.925 than in patients with LHL15 > or = 0.925 (P = 0.033). CONCLUSION: 99mTc-GSA scintigraphy is useful in evaluating the hepatic functional reserve in patients with biliary malignancies.

Adult↗
PubMed1999

Biological consequences of irradiation by low doses of technetium 99m: ultrastructural studies, p53 protein expression and cytogenetic effects.

Few studies concerning the potential genetic effects of diagnostic radionuclides used in nuclear medicine have been reported. The aim of this study was to evaluate the biological and cytogenetic consequences of two technetium 99m-labelled radiopharmaceuticals. Ultrastructural modifications of pulmonary cells were first investigated after injection of 99mTc labelled microspheres in the rat. On the same irradiated cells, nuclear expression of p53 protein was assessed using immunohistochemistry. Despite very high previously calculated doses delivered to pulmonary cells, no morpholological cell damage and no significant increase of nuclear expression of the p53 were noted. There was no correlation between the calculated dose and the ultrastructural biological damage. Secondly, a specific in vitro curve, activity/number of unstable chromosomal aberrations, corresponding to physical characteristics of 99mTc, was established to verify the potentiality of 99mTc to induce such aberrations. In vivo, cytogenetic effects were assessed on blood samples of 5 patients with various arthrosic and periarthrosic diseases obtained after bone scintigraphy. Aberration frequencies of both in vitro and in vivo irradiated lymphocytes were determined using the classical Fluorescence Plus Giemsa technique. No cytogenetic effects appeared with the routinely 99mTc injected activities as predicted by the in vitro curve.

Adolescent↗
PubMed2001

Technetium Tc 99m DTPA galactosyl human serum albumin to measure changes in hepatic functional reserve after transcatheter arterial embolization of the liver.

OBJECTIVE: To describe the acute and subacute changes in hepatic functional reserve using technetium Tc 99m diethylenetriaminepentaacetic acid galactosyl human serum albumin (Tc-99m DTPA GSA) in patients with hepatocellular carcinoma and liver cirrhosis who had undergone transcatheter arterial embolization (TAE). METHODS: Sequential Tc-99m DTPA GSA hepatic scintigraphies were performed prospectively in 26 consecutive patients with hepatocellular carcinoma and liver cirrhosis approximately 1 week before, 2 days after and 1 month after TAE. Counts per 10 seconds of the heart region of interest on 3- and 15-min images and the liver region of interest on a 15-min image were calculated. RESULTS: Clearance index decreased (p < 0.001) and receptor index and modified receptor index increased 2 days after TAE (p < 0.001 and p = 0.004, respectively), but these changes did not persist 1 month later. CONCLUSION: This study has established an expected pattern of behaviour of the liver after TAE, which could be used to monitor progress of patients who undergo the procedure.

Aged↗
PubMed2002

[Correlation of the uptake of technetium-99m methoxyisobutyl isonitrile with expression of multidrug resistance genes mdr-1 and MRP in human lung cancer].

OBJECTIVE: To investigate the relationship between the uptake of technetium-99m methoxyisobutyl isonitrile ((99m)Tc-MIBI) and the expression of multidrug resistance genes mdr-1 and MRP in lung cancer so as to guide chemotherapy. METHODS: Eighteen lung cancer patients were given 1 110 MBq(99m)Tc-MIBI intravenously. Chest single-photon emission-computed tomography was performed 60 and 120 min after the injection. The early and delay uptake rates and retain index of (99m)Tc-MIBI were calculated by the count ratio of the lung lesion to contralateral normal lung tissue. The expressions of mdr-1 and MRP genes in specimens of lung cancer and normal lung tissues near the cancers resected during operation among the 27 patients were detected with RT-PCR method. RESULTS: The positive rate of (99m)Tc-MIBI in the chest of lung cancer patients was 83.3% (15/18). The early uptake ratio of imaging in lung cancer patients was 1.99 +/- 0.64. After time decay correction, the rate of target to background and the retain index in 13 delay imagings were 2.06 +/- 0.69 and -45% approximately 33% respectively. In specimens of lung cancer, the positive expression rates of mdr-1 and MRP were 22.2%(6/27) and 63%(17/27) with the expression amount of 0.39 +/- 0.1 and 0.23 +/- 0.17 respectively. In specimens of normal lung tissues near lung cancer, the positive expression rates of mdr-1 and MRP genes were 35%(7/20) and 45.0%(9/20) with the expression amount of 0.44 +/- 0.14 and 0.17 +/- 0.18 respectively. In lung cancer tissues, the positive rate of MRP was higher than that of mdr-1 (P < 0.05), however, in the tissues near lung cancer, no significant difference was found between the positive rate of MRP and that of mdr-1 (P >< 0.05). There was no marked correlation (P >< 0.05) among the co-expression or expression of mdr-1 and/or MRP and the early uptake or retain index in lung cancer. CONCLUSION: The primary chemoresistance of lung cancer has not significant correlation to the expression of multidrug resistance genes mdr-1 and MRP. Other resistance mechanism may exist. (99m)Tc-MIBI imaging has not much clinical value in predicting the expression of mdr-1 and MRP genes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗