Biomedical subjects

G J Teule

Publications and source records attributed to G J Teule.

At least 37 records · Page 2Linked to original sources

PubMed1997

Sentinel node biopsy in melanoma patients: dynamic lymphoscintigraphy followed by intraoperative gamma probe and vital dye guidance.

Biopsy of the first tumor-draining lymph node (sentinel node, SN) is bound to become the procedure of choice in regional staging of melanoma patients. A tumor-negative SN virtually excludes lymphatic metastases and obviates the need for lymph node dissection. The aim of this study was to combine the advantages of three known techniques to improve the yield of successful SN biopsies. A total of 150 drainage areas in 135 patients was evaluated. First, preoperative dynamic and static lymphoscintigraphy was performed after injection of technetium 99m colloidal albumin. In all patients one to three focal accumulations, concordant with SNs, were seen in the lymphatic drainage areas, in 97% within 20 minutes from injection of the tracer. Peroperative identification of the SN, 2 to 24 hours after injection of the tracer, was done with a handheld gamma probe to estimate the optimal site for the small incision and to guide preparation. Vital dye was injected just preoperatively and served to facilitate the final identification and biopsy of the SN. A total of 216 SNs were biopsied. Micrometastases were found in 39 SNs in 30 drainage areas, and in 22 of the 30 of the SN was the only node harboring tumor. In 5 of 30 drainage areas, the SN did not contain blue dye and would not have been found without the gamma probe. Up to now (follow-up 233-691 days) no recurrence has developed in the lymphatic drainage areas where the SN was tumor-free. It was concluded that by combining these three techniques the SN could be detected and excised in all patients. The procedure combines a steep learning curve with high sensitivity.

Biopsy, Needle↗

PubMed1997

Radionuclide therapy for prostate cancer lumbar metastasis prolongs symptom-free survival in a rat model.

OBJECTIVES: The present study was initiated to explore the effects of hydroxyethylidene diphosphonate labeled with rhenium 186(186Re-HEDP) treatment on the progression of lumbar skeletal metastasis in an animal model and to correlate the eventual treatment efficacy with the radioisotope tissue distribution. METHODS: The effect of 186Re-HEDP on the progression of lumbar metastasis from prostate cancer was investigated in the Copenhagen rat model. Metastatic prostate tumor deposits were induced in male rats by tail vein injection of R3327-MATLyLu prostate tumor cells under concomitant clamping of the inferior caval vein. The development of clinical symptoms such as onset of hind leg paralysis and urinary bladder swelling was monitored and related to the presence of tumor cells within histologic sections of L-5 and L-6 vertebrae. RESULTS: The 186Re-HEDP administration, given either 1 day or 8 days after surgical induction of lumbar metastasis, could significantly increase the symptom-free survival of the animals. These results were confirmed by a significant decrease in the presence of histologically detectable tumor tissue. Biodistribution studies demonstrated the uptake of the major part of the radioisotope within bone tissue. Uptake of radioactivity within the lumbar vertebrae on a microscopic scale, as shown by phosphor screen autoradiography, was concentrated in areas of bone formation and turnover. Signs of radiotoxicity, such as bone marrow replacement by fat cells and the absence of megakaryocytes, were observed. CONCLUSIONS: The results show that radionuclide treatment using 186Re-HEDP is a potentially efficacious treatment option in prostate cancer disseminated to the skeleton. The optimal treatment dose should be determined carefully and aimed at acceptable levels of myelotoxicity.

Animals↗

PubMed1997

Evaluation of heart-to-organ ratios of 123I-BMIPP and the dimethyl-substituted 123I-DMIPP fatty acid analogue in humans.

Radioiodinated fatty acid analogues modified by methyl-substitution are used for single photon emission tomography (SPET) imaging of the heart. The effect of mono- and dimethyl-substitution on heart-to-organ ratios was investigated in humans to evaluate their relative merits for SPET image quality. Planar total body scans were performed in fasting patients with coronary artery disease, but without heart failure, 1 h after administration of 111 MBq 15-(p-[I-123]-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP, n = 7) or 111 MBq 15-(p-[I-123]-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP, n = 4). Because these branched fatty acids are used for cardiac imaging, we focused on heart-to-organ (heart/organ) ratios by comparing small regions of interest in heart, liver, lung, muscle and bladder. Both tracers showed good visualization of the heart. DMIPP showed a relatively high liver uptake: the heart/liver ratios for DMIPP and BMIPP were 0.39 +/- 0.05 and 1.00 +/- 0.12, respectively (P < 0.0001). Increased lung activity was found for BMIPP, with a heart/lung ratio of 1.63 +/- 0.17 versus 2.32 +/- 0.28 for DMIPP (P < 0.001). In contrast to DMIPP, BMIPP also showed increased activity in the bladder. In conclusion, BMIPP and DMIPP show different distribution patterns. Despite the more favourable heart/lung ratios for DMIPP, the high liver uptake affects cardiac SPET image quality and therefore BMIPP appears to provide superior cardiac SPET image quality in humans.

Blood Glucose↗

PubMed1997

Acute lung injury after aortic surgery: the relation between lung and leg microvascular permeability to 111indium-labelled transferrin and circulating mediators.

BACKGROUND: Aortic surgery is a risk factor for acute lung injury and this may relate to ischaemia/reperfusion (I/R) of the lower body and release of inflammatory mediators. The aim of this study was to define the changes in microvascular protein permeability and circulating inflammatory mediators after aortic surgery. METHODS: In 11 consecutive patients who underwent elective aortic surgery microvascular permeability in lung and leg was measured before and a median of 2.8 hours after completion of surgery using 111indium (In)-labelled transferrin and 99mtechnetium (Tc)-labelled red blood cells, yielding a protein leak index (PLI) that is specific for protein permeability. Circulating leucocyte counts and levels of inflammatory mediators were determined. RESULTS: In the lung the PLI rose from a median of 0.6 (range -0.5 to 2.2) x 10(-3)/min before surgery to 5.4 (-2.3 to 33.5) x 10(-3)/min after surgery, and in the leg from 0.3 (-1.6 to 1.7) x 10(-3)/min to 5.0 (1.0 to 27.8) x 10(-3)/min. The increase in PLI in the lung was related to that in the leg. Levels of activated complement C3a and tumour necrosis factor-alpha did not change, but levels of interleukin (IL)-6, IL-8 and elastase-alpha 1-antitrypsin increased. After surgery there was slight neutrophilia and the leucocyte counts were inversely related to the IL-8 level. The rise in lung but not in leg PLI was greatest in patients with the highest IL-8 levels and the lowest leucocyte counts. CONCLUSIONS: Early after aortic surgery microvascular protein permeability increases in the leg and lung. Leg I/R injury may result in neutrophil activation and release of IL-8, which may induce neutrophil sequestration and subsequently increased pulmonary microvascular permeability. These findings may help to explain the occurrence of acute lung injury after I/R in man.

Adult↗

PubMed1997

Impact of lymphoscintigraphy on sentinel node identification with technetium-99m-colloidal albumin in breast cancer.

UNLABELLED: Identification of the sentinel node by using colloidal tracers and a gamma probe or lymphoscintigraphy could be an effective alternative for the complicated original dye-oriented approach. We studied the sentinel node detection rate using early and delayed imaging in breast cancer patients. METHODS: Thirty-seven patients were imaged 2 hr and 18 hr after peritumoral injection of 99mTc-colloidal albumin. Preoperatively, axillary foci were located with a handheld gamma probe that was also used to isolate radiolabeled nodes from the axillary dissection specimens. The predictive value of the sentinel node for the axillary tumorstatus was evaluated with histological examination. RESULTS: Two and 18 hr after injection, lymphoscintigraphy revealed one to three separate axillary lymph nodes in 33 and 34 patients, respectively. In 30 patients the axillary foci were easily localized with the gamma probe preoperatively. In all 34 patients (92%), with visualized axillary foci, at least one radioactive sample could be retrieved using the gamma probe (total 53 samples). Metastases were found in the sentinel nodes of 11 patients, in seven of 11 being the only tumor-positive lymph node in the axilla. There were no false-negative sentinel nodes. CONCLUSION: The selective targeting and prolonged intranodal retention of 99mTc-colloidal albumin allows successful sentinel node identification in most (92%) patients.

Aged↗

PubMed1996

Absorbed dose distribution of the auger emitters 67GA and 125I and the beta-emitters 67CU, 90Y, 131I, and 186RE as a function of tumor size, uptake, and intracellular distribution.

PURPOSE: The influence of tumor volume, uptake of radioactive compounds in cells of tumors and normal tissues, and characteristics of the emitted ionizing particles on the efficacy of systemic radiation were studied. METHODS AND MATERIALS: The influence of these variables was assessed using a point kernel approach combined with a distance histogram technique. Simulation calculations were performed to assess dose distributions for three tumor sizes (phi = 200 microns, 2 mm, or 2 cm) and six radionuclides: 67Ga, 125I, 67Cu, 90Y, 131I, and 186Re. RESULTS: The energy deposition patterns depended on the relation of the tumor size and range of the emitted particles. Selective uptake was especially important in cases where the range was short compared to the dimension of the tumor. CONCLUSION: To attain a high dose for treatment of micrometastases, the use of Auger and conversion electron emitters (67Ga and 125I) or beta-emitters with emission spectra including low energetic electrons (67Cu and 131I) was recommended. The results demonstrated the complementary nature of selectivity of energy deposition and crossfire. This implied that for tumor cells or areas with reduced uptake, crossfire from radioactivity in surrounding cells or areas with selective uptake would be provided by intermediate (conversion electrons) or long-range (beta-particles) emissions.

Dose-Response Relationship, Radiation↗

PubMed1996

Radiotoxic effect and dosimetry of 67GA in multicellular spheroids as compared to single cells of the lymphoma cell line U715.

PURPOSE: The purpose of the present study was to investigate if there were differences between U715 spheroids and single cells in the radiotoxic effect of 67Ga on cell growth and clonogenic capacity in vitro and to generate dosimetric approaches for the multicellular tumor model. METHODS AND MATERIALS: Human lymphoma U715 cells were cultured in vitro as single cells and multicellular spheroids, grown with the use of a combination of fibrin clot technique, spinner flasks, and liquid-overlay culture. Cells were incubated with 2.96-8.88 MBq/ml 67Gallium for 4 days. Spheroids were dispersed to single cells by treatment with plasmin. Residual proliferative and clonogenic capacity after 67Ga incubation were assayed using the MTT-test and clonogenic test, respectively. Autoradiography was performed with 1 microm sections and Ilford L4 liquid photographic emulsion. Dosimetric approaches were made, based on the MIRD-approach. RESULTS: During 67Ga incubation proliferation was inhibited. The residual proliferative or clonogenic capacity was inhibited by 8.88 MBq/ml for 39 and 88%, respectively. For single cells with 6.66 MBq/ml these inhibitions were 64 and 96%, respectively. Autoradiography showed an homogeneous distribution of 67Ga in spheroids and single cells. In single cells a 2.1-3.5 times higher 67Ga uptake/cell than in spheroids produced an equitoxic effect. The uptake parameters were implemented in new dosimetric approaches and showed that the efficacy of intracellular 67Ga was two times higher in spheroid clusters than in single cells due to energy deposition of internal conversion electrons within the cell clusters with a mean diameter size of nine cells. Both for proliferative and clonogenic capacity the exponential survival curves were superimposed. CONCLUSIONS: With the new approaches made in our dosimetric model the discrepancy found between 67Ga accumulation and radiotoxic effect in spheroids as compared to single cells can be explained by additional effects of the crossfire of internal conversion electrons within clusters of about nine cells in diameter in spheroids. Only twice as much 67Ga was needed to reach equitoxic absorbed doses in spheroids than was needed in single cells. Such might be important for the use of 67Ga treatment of small metastasis of malignant lymphoma.

Autoradiography↗

PubMed1996

What is the cause of pulmonary oedema after acute myocardial infarction? A case study.

A patient is described with an acute myocardial infarction (AMI) and pulmonary oedema, necessitating mechanical ventilation, at a mean pulmonary capillary wedge pressure (PCWP) below 13 mmHg. The 67Ga-transferrin pulmonary leak index (PLI), a measure of microvascular permeability, was normal. A study of the course of the PCWP revealed intermittent elevations up to 22 mmHg, owing to intermittent mitral regurgitation. Pulmonary oedema after an AMI can thus be caused by pressure factors, even at sporadic elevations of PCWP, following intermittent, ischaemia-induced dysfunction of the posterior papillary muscle. Conversely, the measurement of a normal 67Ga-PLI may help to diagnose hydrostatic as opposed to permeability pulmonary oedema, if sporadic elevations of the PCWP are not recognised.

Humans↗

PubMed1996

Prediction of recovery of myocardial dysfunction after revascularization. Comparison of fluorine-18 fluorodeoxyglucose/thallium-201 SPECT, thallium-201 stress-reinjection SPECT and dobutamine echocardiography.

OBJECTIVES: We compared three techniques to predict functional recovery after revascularization. BACKGROUND: Recently, fluorine-18 (F-18) fluorodeoxyglucose in combination with single-photon emission computed tomography (SPECT) has been proposed to identify viable myocardium, Thallium-201 reinjection and low dose dobutamine echocardiography are used routinely for this purpose. METHODS: Seventeen patients (mean [+/- SD] left ventricular ejection fraction 36 +/- 11%) were studied. Regional and global ventricular function were evaluated before and 3 months after revascularization by echocardiography and radionuclide ventriculography, respectively. Myocardial F-18 fluorodeoxyglucose uptake (during hyperinsulinemic glucose clamping) was compared with rest perfusion assessed with early thallium-201 SPECT. On a separate day, low dose dobutamine echocardiography and post-stress thallium-201 reinjection SPECT were simultaneously performed. RESULTS: The sensitivities for F-18 fluorodeoxyglucose/thallium-201, thallium-201 reinjection and low dose dobutamine echocardiography to assess recovery were 89%, 93% and 85%, respectively; specificities were 77%, 43% and 63%, respectively. Stepwise logistic regression indicated that F-18 fluorodeoxyglucose/ thallium-201 was the best predictor. In hypokinetic segments, the combination of F-18 fluorodeoxyglucose/thallium-201 and low dose dobutamine echocardiography was the best predictor. Global function improved (left ventricular ejection fraction increased > 5%) in 6 patients and remained unchanged in 11. All three techniques correctly identified five of six patients with improvement. Fluorine-18 fluorodeoxyglucose/thallium-201 identified all patients without improvement; low dose dobutamine echocardiography identified 9 of 11 without improvement; and thallium-201 reinjection identified 6 of 11 patients without improvement. CONCLUSIONS: Fluorine-18 fluorodeoxyglucose/thallium-201 SPECT was superior to the other techniques in assessing functional recovery. Integration of metabolic and functional data is necessary, particularly in hypokinesia, for optimal prediction of improvement of regional function.

Adult↗

PubMed1996

Effect of modulation of the transferrin receptor on gallium-67 uptake and cytotoxicity in lymphoma cell lines.

Gallium-67 is a radionuclide that accumulates in haematological malignancies and is used for diagnostic purposes. Uptake of 67Ga into the cell occurs via the transferrin receptor, which is differentially expressed during the various cell cycle phases. With the aim of selectively increasing 67Ga uptake, we studied whether the transferrin receptor (TfR) expression could be modulated in the U937 and U715 lymphoma cell lines by cytostatic drugs inducing cell cycle phase accumulation. We tested clinically relevant drugs such as 1-beta-D-arabinofuranosylcytosine (Ara-C), hydroxyurea and methotrexate. Cytotoxicity was determined by testing the clonogenic capacity of the lymphoma cell lines. All three drugs induced an increase in S-phase content, TfR expression and 67Ga uptake in U937 and U715 single cells. The combinations of drugs and 67Ga resulted in an additive effect on the clonogenic capacity. In U937 spheroids, cultured by the fibrin clot technique, we found an accumulation in the S-phase too as well as an increase of the transferrin receptor expression after Ara-C preincubation. As in single cells 67Ga uptake was increased without synergistic effects on the clonogenic capacity. In conclusion, priming with drugs induces increased transferrin receptor expression and 67Ga uptake. Inhibition of clonogenic capacity was additive rather than synergistic.

Antineoplastic Agents↗

PubMed1996

The 67gallium pulmonary leak index in assessing the severity and course of the adult respiratory distress syndrome.

OBJECTIVE: To establish the value of the 67Gallium (Ga) pulmonary leak index, a marker of increased permeability edema of the lungs, in assessing the severity and course of the adult respiratory distress syndrome (ARDS). DESIGN: Prospective observational study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Seventeen consecutive, mechanically-ventilated ARDS patients. Eleven patients (recovering from ARDS) improved, as defined by the ability to taper the level of positive end-expiratory pressure (PEEP) to 0 cm H2O at a median of 7 days after admission. Ten patients survived. Six patients did not recover and died a median of 3.5 days after admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The pulmonary leak index (i.e., upper limit of normal 14.1 x 10(-3)/min) was measured within 72 hrs after admission, and repeated within 48 hrs at the time of recovery in recovering patients. At admission and recovery, respiratory variables were recorded and a lung injury score was calculated. At admission, the pulmonary leak index was increased in each patient to 32.3 (range 15.6 to 52.4) and 28.7 (range 26.0 to 40.8) x 10(-3)/min in recovering and nonrecovering patients, respectively (NS). Groups did not differ with respect to the oxygenation ratio, the level of PEEP, radiographic abnormalities, and the lung injury score. At recovery, the pulmonary leak index in recovering patients had decreased in each patient and had normalized in four patients, averaging 15.2 (range 5.6 to 25.9) x 10(-3)/min, concomitantly with an increased oxygenation ratio, less radiographic abnormalities, and a decreased lung injury score (p < .01 vs. admission). For pooled recovering and nonrecovering patient data, the pulmonary leak index directly related to the lung injury score (p < .005). CONCLUSIONS: The 67Ga pulmonary leak index may be a clinically useful tool to quantify the severity and course of ARDS, since clinical recovery from the syndrome may be characterized by amelioration of increased microvascular permeability.

Adult↗

PubMed1996

Diagnostic value of the gallium-67 pulmonary leak index in pulmonary edema.

UNLABELLED: We studied the value of a noninvasive, bedside, dual-radionuclide method (67Ga-circulating transferrin and 99mTc-red blood cells) to measure pulmonary microvascular permeability in efforts to discriminate between pulmonary edema due to adult respiratory distress syndrome (ARDS) and hydrostatic pulmonary edema (HPE). METHODS: Patients had respiratory insufficiency and bilateral alveolar pulmonary edema on chest radiographs. All patients, except one, were mechanically ventilated. Patients, were divided into groups according to various sets of etiologic, hemodynamic and ventilatory factors. Group 1 (n = 8) had risk factors for HPE only. Group 2 (n = 5) had risk factors for both ARDS and HPE, such as a pulmonary capillary wedge pressure (PCWP) above 18 torr. Group 3 (n = 13) had risk factors for ARDS only and a PCWP below 18 torr. Patients were also classified on the basis of a lung injury score, using radiographic and ventilatory variables. Group 4 (n = 12) had a score below 2.5 and Group 5 (n = 14) above 2.5, arbitrarily defined as ARDS. Any radioactivity measurements over the lungs and in blood within 72 hr after admission were used to calculate the 1 hr pulmonary leak index as a measure of microvascular permeability (upper limit of normal 14.1 x 10(-3).min-1). RESULTS: The PLI ( x 10(-3).min-1) was median 10.2 (range 4.4-16.2) in Group 1, 26.8 (14.2-31.9) in Group 2 and 32.3 (23.0-52.4) in Group 3 (p < 0.001). It was 13.3 (4.4-39.9) in Group 4 and 31.1 (14.2-52.4) in Group 5 (p < 0.01). Using the various definitions, the sensitivity of a supranormal pulmonary leak index for ARDS was 100% and the specificity varied between 46% and 75%. In receiver operating characteristic curves, the pulmonary leak index performed best when ARDS and HPE were defined on the basis of risk factors only, and performed better than hemodynamic and equally well as ventilatory variables in discriminating between edema types, if definitions of the latter were mainly based on hemodynamic and ventilatory variables, respectively. CONCLUSION: The 67Ga pulmonary leak index is a useful tool to differentiate ARDS from HPE.

Aged↗

PubMed1996

Comparison of myocardial uptake of fluorine-18-fluorodeoxyglucose imaged with PET and SPECT in dyssynergic myocardium.

UNLABELLED: PET with 18F-fluorodeoxyglucose (FDG) can detect viable myocardium and predict functional recovery after revascularization. The use of PET for clinical routine, however, is limited. Recently, imaging FDG with SPECT was proposed. The aim of this study was to compare the diagnostic value of FDG-PET and FDG-SPECT in the detection of viable myocardium in segments with abnormal wall motion. METHODS: Twenty patients with previous myocardial infarction were studied. All underwent FDG-PET and FDG-SPECT during hyperinsulinemic glucose clamping. Regional perfusion was assessed with 13N-ammonia PET and early resting 201TI- SPECT. Regional wall motion was assessed with two-dimensional echocardiography. The agreement between FDG/13N-ammonia PET and FDG/201TISPECT to detect viability in dyssynergic myocardium was 76%. On a patient basis, PET and SPECT yielded comparable results in 17 of 20 patients. In a subgroup of patients with LVEF < or = 35% (n = 12), all PET and SPECT viability data were identical. CONCLUSION: This study shows a good correlation between the detection of viability in dyssynergic myocardium with FDG/13N-ammonia PET and FDG/201TI SPECT, both on a segmental and patient basis.

Ammonia↗

PubMed1995

Influence of high and low plasma insulin levels on the uptake of fluorine-18 fluorodeoxyglucose in myocardium and femoral muscle, assessed by planar imaging.

The aim of this study was to optimize the metabolic conditions for planar myocardial fluorine-18 fluorodeoxyglucose (FDG) imaging. The effects of high and low insulin levels during euglycaemic clamping on myocardial and femoral muscle FDG uptake were compared since insulin plays a major role in glucose metabolism. FDG uptake in 11 patients was studied using planar scintigraphy. Patients were studied twice: in the low-dose insulin protocol (LDI), insulin was infused at a rate of 20 mU/kg per hour, starting 1 h before FDG administration, while in the high-dose insulin protocol (HDI) it was infused at a rate of 100 mU/kg per hour. Glucose infusion rate was adjusted according to frequently determined blood glucose levels. Somatostatin was infused to block endogenous insulin release. Planar images were obtained from the thorax region and femoral muscles. Regions of interest were drawn over normal and abnormal myocardial areas (based on angiographic and thallium-201 data) and over lung, liver and muscle areas. After clamping, insulin levels during LDI and HDI at t = 60 were 30.6 +/- 13.3 and 129.6 +/- 30.5 mU/l respectively (P < 0.0001). Femoral muscle uptake was significantly higher during HDI (P < 0.001). Uptake in normal and abnormal myocardial areas did not differ between the two protocols. Heart/lung ratios (NS) and heart/liver ratios (P < 0.05) increased during HDI. It may be concluded that planar FDG imaging is influenced by plasma insulin levels. The euglycaemic hyperinsulinaemic clamp technique, although more demanding, gives an adjustable metabolic steady state without significantly altering the FDG uptake patterns in normal and abnormal myocardial regions. The image quality of planar FDG images improves due to lower background uptake of FDG during clamping with high plasma insulin levels.

Case-Control Studies↗

PubMed1995

Relation between myocardial uptake of thallium-201 chloride and fluorine-18 fluorodeoxyglucose imaged with single-photon emission tomography in normal individuals.

Recently, we have demonstrated the feasibility of imaging myocardial uptake of fluorine-18 fluorodeoxyglucose (FDG) with single-photon emission tomography (SPET) using a specially designed collimator. Thallium-201 was used to determine distribution of perfusion for comparison with FDG uptake. However, regional 201Tl and FDG activities may be different, based on differences in tracer attenuation and the use of different collimators. To study the relation between tracer activities imaged with SPET, nine healthy individuals underwent resting 201Tl SPET and FDG SPET during a hyperinsulinaemic euglycaemic clamp. The SPET data were analysed semiquantitatively, using circumferential profiles. Mean profiles of midventricular short-axis slices showed no significant difference between 201Tl and FDG activity. Regional fluctuations were similar for FDG and 201Tl; the highest tracer activities were observed in the lateral wall and the lowest activities in the septum. Finally, pooled data (n = 1620 segmental activities) in nine individuals showed a linear correlation (P < 0.0001) between 201Tl and FDG activity: FDG = 0.76 201Tl + 0.23 (r = 0.70). These data demonstrate the absence of major differences between regional 201Tl and FDG activity in normal myocardium, suggesting that no separate 201Tl and FDG SPET reference values are needed for comparison with patient studies.

Adult↗

PubMed1995

Radiotoxicity of 67-gallium on myeloid leukemic blasts.

Promising clinical results are obtained with radiolabeled antibodies in leukemia patients. 67Gallium (67Ga) is a radionuclide that accumulates in many malignant tissues without need for a monoclonal antibody. For this reason, the use of 67Ga as a therapeutic agent is appealing. In the present we study, we report data about the radiotoxicity of 67Ga on peripheral blast cells of 23 patients with acute myelogenous leukemia (AML) in vitro. Isolated blast cells were incubated for 4 days with 0.74 MBq/ml (20 microCi/ml), 1.48 MBq/ml (40 microCi/ml) or 2.96 MBq/ml (80 microCi/ml) 67Ga. Compared with non-irradiated control cells proliferation during incubation was almost abolished. Clonogenic survival was measured by a colony forming unit assay (CFU-assay). In 13 of the 23 patients (56%) sufficient colony growth was observed for evaluation. The mean clonogenic survival of blasts after incubation with 0.74 MBq/ml and 2.96 MBq/ml 67Ga was 22.5, 11.3 and 3.5%, respectively. In some cases colony growth was completely abolished after incubation with only 0.74 MBq/ml 67Ga. No correlation was found between cellular 67Ga-uptake, (micro)dosimetry and transferrin receptor density (CD-71) via which 67Ga enters the cell. In vitro the blasts received a dose of > 10 Gy in 9 of the 2.96 MBq/ml, in 3 of the 1.48 MBq/ml and in 2 of the 0.74 MBq/ml incubations. In one patient, even a radiation dose > 40 Gy was reached. Low dose rate irradiation is known to arrest cells in G2/M-phase of the cell cycle, but no such arrest was observed during incubation with 67Ga. Thus, 67Ga induces clonogenic cell death in leukemic blasts. Cellular uptake of 67Ga in vitro varies between patients and can be very high in some patients. The easy availability, low costs and absence of immunological problems warrant further investigation of the therapeutic potential of 67Ga in refractory or relapsed AML patients.

Acute Disease↗

PubMed1995

High-dose gallium-67 therapy in patients with relapsed acute leukaemia: a feasibility study.

Gallium-67 (67Ga) accumulates in malignant tissues via the transferrin receptor without need for a monoclonal antibody and emits cytotoxic low-energy electrons. In this study we investigated the feasibility, pharmacokinetics, toxicity and preliminary efficiency of high-dose 67Ga injected intravenously (i.v.) in patients with acute leukaemia not responding to conventional therapy. Twelve doses of 36-105 mCi of Gallium67 citrate were administered as a push injection to eight patients with resistant leukaemia in a pilot study. All five patients with acute myeloid leukaemia (AML) and three patients with acute lymphoblastic leukaemia (ALL) had resistant disease or resistant relapse. No (sub)acute toxicity was observed. Independent of the administered dose, whole-blood radioactivity levels 10 min after administration measured only 1.25 +/- 1.39 microCi ml-1, indicating a large volume of distribution. Urine excretion in the first 24 h ranged from 18% to 51.5% (median 29.5%) of the administered dose. Cellular uptake of 67Ga was less than in previous in vitro studies. Whole-body radiation dose was estimated to be 0.25 +/- 0.03 cGy mCi-1. Red marrow dose was estimated to be between 0.18 +/- 0.02 and 0.97 +/- 0.12 cGy mCi-1. One definite response was observed in an ALL patient with disappearance of skin lesions, normalisation of the enlarged spleen and profound leucopenia. Three other patients showed transient reductions in white blood cell counts without disappearance of blasts from the peripheral blood. We conclude that high-dose i.v. 67Ga can be safely administered but that the uptake of 67Ga in blast cells must increase to make 67Ga therapeutically useful in patients with relapsed leukaemia.

Adult↗

PubMed1995

Myocardial F-18 fluorodeoxyglucose imaging by SPECT.

F-18 fluorodeoxyglucose (FDG) in combination with positron emission tomography (PET) is used in patients with coronary artery disease to detect viable myocardium. It was shown that FDG PET is highly accurate in predicting reversibility of cardiac function after revascularization when viable tissue is present. Because PET centers are not widely available, the clinical use of FDG is limited. The authors have shown in another study that imaging 511 keV with planar scintigraphy and a special collimator is feasible. Furthermore, they have studied myocardial FDG uptake in normal volunteers and in patients with coronary artery disease using SPECT. Recently, they have studied the value of FDG SPECT to predict recovery of contractile function before revascularization in patients undergoing bypass surgery. It appears that the FDG SPECT approach is feasible and can predict reversibility of wall motion abnormalities. Further studies are needed to compare FDG SPECT with other techniques for the detection of viable myocardium.

Coronary Disease↗