Kinetics and Fate of 111Indium-Oxine Labelled Blood Platelets in Asplenic Subjects

1980 ◽  
Vol 44 (02) ◽  
pp. 100-104 ◽  
Author(s):  
Anthon duP Heyns ◽  
Matthys G Lötter ◽  
Philip N Badenhorst ◽  
Otto van Reenen ◽  
Henry Pieters ◽  
...  

SummaryThe survival, tissue distribution and fate of 111Indium-oxine labelled autologous platelets was studied in four asplenic subjects with serial blood sampling, scintillation camera and computer-assisted imaging. Mean 111In-platelet recovery in the circulation was 89 ± 13% (± 1 SD). Platelet survival curves fitted a linear function best and was 238 ± 41 h. The shape of the survival curves of normal and asplenic subjects differed: in the asplenic subjects the curve was linear whereas that of normal subjects was significantly more curvilinear if analyzed by least squares computer fitting to a gamma function. Early hepatic 111In-activity was significant and transient and ascribed to the "collection injury". As labelled platelets disappeared from the circulation, 111Inactivity in the liver increased progressively and linearly to reach 42.5 ± 14.1 % of whole body activity at 240 h. Radioactivity also accumulated in the bone marrow, but could not be demonstrated in the vasculature of the lower limbs. These results would indicate that in asplenic subjects the major sites of destruction of senescent platelets are the liver and bone marrow.

Blood ◽  
1980 ◽  
Vol 56 (1) ◽  
pp. 58-63 ◽  
Author(s):  
PJ Smith ◽  
CW Jackson ◽  
MA Whidden ◽  
CC Edwards

Hypertransfusion can enhance myeloid recovery after bone marrow depletion, but its influence on thrombopoietic recovery has not been previously defined. We have studied the pattern of platelet and megakaryocyte recovery in mice hypertransfused after receiving 350 rad whole body irradiation. The platelet counts of the hypertransfused group showing an initial fall due to hemodilution in the expanded blood volume and then fell to a lower nadir than that of the control mice. The rate of platelet recovery was more rapid in the hypertransfused mice. Bone marrow megakaryocyte concentrations in both groups showed a degenerative phase, abortive rise, and regenerative phase. The decrease in megakaryocytes was the same in both groups. The hypertransfused mice showed a greater abortive rise in megakaryocyte concentration preceded by the appearance of a greater number of large megakaryocytes in the bone marrow. However, the most striking effect of hypertransfusion was on megakaryocyte recovery. Although the time of onset of recovery was not different, the rate of recovery was approximately twice as rapid in the hypertransfused group. Administration of daily erythropoietin to hypertransfused mice abolished this more rapid recovery. Thus, the presence of a simultaneous demand for erythroid precursors does affect the rate of megakaryocyte regeneration. Just as the more rapid recovery of granulopoiesis following hypertransfusion may be clinically beneficial, the more rapid reconstitution of thrombopoiesis may also offer clinical advantage in some circcumstances.


1999 ◽  
Vol 38 (03) ◽  
pp. 85-89 ◽  
Author(s):  
M. Reinhardt ◽  
E. Nitzsche ◽  
E. Moser ◽  
Th. Krause

Summary Aim: The purpose of this study was to elucidate the frequency of photopenic lesions in patients without known tumour disease by using bone marrow scintigraphy with Tc-99m labeled anti-NCA-95. Methods: Whole body immunoscintigraphy (IS) was performed in 141 consecutive patients with fever of unknown origin. The age ranged between 20 and 88 years with a mean age of 57 years. None of the patients had known tumour disease. Scans were evaluated with respect to photopenic lesions and to bone marrow distribution. Results: IS showed bone marrow defects in the axial skeleton in 16 patients (11 %). With the help of the typical scintigraphic defect pattern, the cause of the lesions was clearly identified as degenerative changes in four patients and in one patient as due to prior sternotomy. In the remaining 11 patients the origin of the defects became evident when the case history or additional imaging was consulted. The mean age of these 16 patients was 69 years ranging from 50 to 88 years. There was an age-related frequency of defects. 10% of the patients from 50 to 59 years showed defects, 60-69 years 9%, 70-79 years 30%, and 33% of the patients from 80 to 89 years had defects. IS was not hampered by tracer uptake to liver or spleen in 93 patients. Left caudal ribs were obscured in 48 patients with intense tracer uptake to the spleen. No or markedly reduced tracer uptake was found in caput humeri and caput femori in 94 and 82 patients, respectively. Patchy tracer uptake to the bone marrow of the limbs was seen in 13/62 patients showing marrow expansion in the lower limbs and 14/55 with marrow expansion in the upper limbs. The patchy pattern was asymmetric in 12 of these patients. Conclusion: The results of the present study reveal that using Tc-99m NCA-95, photopenic lesions of the bone marrow are rarely seen in patients without known malignant disease. The occurrence of benign lesions is age-related. The benign cause of the lesion was obvious from location and pattern of the lesion in about 30% of the cases. Evaluation of lesions in the upper and lower limbs may be hindered due to physiological variation of marrow distribution. Nevertheless, IS appears to be well-suited for the detection and localization of bone marrow metastases.


Blood ◽  
1980 ◽  
Vol 56 (1) ◽  
pp. 58-63 ◽  
Author(s):  
PJ Smith ◽  
CW Jackson ◽  
MA Whidden ◽  
CC Edwards

Abstract Hypertransfusion can enhance myeloid recovery after bone marrow depletion, but its influence on thrombopoietic recovery has not been previously defined. We have studied the pattern of platelet and megakaryocyte recovery in mice hypertransfused after receiving 350 rad whole body irradiation. The platelet counts of the hypertransfused group showing an initial fall due to hemodilution in the expanded blood volume and then fell to a lower nadir than that of the control mice. The rate of platelet recovery was more rapid in the hypertransfused mice. Bone marrow megakaryocyte concentrations in both groups showed a degenerative phase, abortive rise, and regenerative phase. The decrease in megakaryocytes was the same in both groups. The hypertransfused mice showed a greater abortive rise in megakaryocyte concentration preceded by the appearance of a greater number of large megakaryocytes in the bone marrow. However, the most striking effect of hypertransfusion was on megakaryocyte recovery. Although the time of onset of recovery was not different, the rate of recovery was approximately twice as rapid in the hypertransfused group. Administration of daily erythropoietin to hypertransfused mice abolished this more rapid recovery. Thus, the presence of a simultaneous demand for erythroid precursors does affect the rate of megakaryocyte regeneration. Just as the more rapid recovery of granulopoiesis following hypertransfusion may be clinically beneficial, the more rapid reconstitution of thrombopoiesis may also offer clinical advantage in some circcumstances.


2001 ◽  
Vol 40 (06) ◽  
pp. 207-214 ◽  
Author(s):  
M. Holländer ◽  
W. Schmidt ◽  
C.-M. Kirsch ◽  
Ch. Alexander

SummaryThe monoclonal antibody MAb-170 is directed against adenocarcinomas of different origin. Recent experience in radioimmunoscintigraphy revealed a positive uptake of this MAb in peritoneal metastases of ovarian carcinoma (FIGO lll/IV). Aim: The present investigation should clarify the question whether this antibody could be of use in an adjuvant intraperitoneal radioimmunotherapy (RIT) in patients with minimal residual disease after first-look surgery. Methods: Four patients underwent intraperitoneal application of Tc-99m MAb-170. Subsequent quantitative whole-body scintigraphy, serum and urine sampling were performed for a 48 h period. In one case tumour tissue specimen were sampled during the first surgical procedure 15 h p.L Results: The quantitative evaluation revealed no relevant accumulation in liver, spleen and bone marrow never exceeding 5 % of the whole-body activity. The critical organs are the kidneys that showed 8 to 11 % uptake at 24 h pi. The effective serum curve had a maximum at 24 h pi, the second phase gave a elimination half-time of 53 h. Assuming the worst case, the mean dose to red bone marrow was 0.3 Gy/370 MBq injected dose (ID). Conclusion: These results confirm that a RIT with Re-186 MAb-170 is feasible with activities of up to 3.7 GBq. A kit for labelling MAb-170 with Perrhenate is under investigation.


Blood ◽  
1967 ◽  
Vol 29 (3) ◽  
pp. 341-353 ◽  
Author(s):  
R. M. HEYSSEL ◽  
L. J. SILVER ◽  
MARIE WASSON ◽  
A. B. BRILL

Abstract 1. The distribution of 14C-5-HT following infusion is different from that of endogenous serotonin. One hour after infusion it is, in major part, a function of the distribution of blood platelets. 2. The spleen in rats is the site of a pool of platelets. Based on both 14C and platelet recovery data in normal and splenectomized animals, this pool approximates 40 per cent of the total circulating platelets. 3. Postsplenectomy thrombocytosis may relate to removal of a platelet reservoir with shift of the platelets normally contained therein to the peripheral circulation. 4. The shape of platelet survival curves in rats is neither strictly linear nor curvilinear but normally is determined primarily by age-related processes in the platelet. Platelet survival curves tend to become curvilinear in thrombocytopenic animals, indicating that there is probably an additional small, fixed random loss of platelets from the circulation. 5. The disappearance of 14C-5-HT from blood platelets approximates but is not completely representative of the disappearance of the platelets themselves. It is probable that elution from platelets and possibly reutilization of platelet label occurs.


Author(s):  
A duP Heyns ◽  
M G Lötter ◽  
P N Badenhorst ◽  
F de Kock ◽  
H Pieters ◽  
...  

Platelets of 7 patients with abdominal aortic aneurysms were labelled with In-lll-oxine prior to surgery. The platelets were reinjected with the patient positioned under a scintillation camera with a computer assisted imaging system. Images were acquisitioned daily, areas of interest selected with the computer, organ radioactivity- quantitated with a geometrical mean method and expressed as a percentage of whole body radioactivity. Platelet survival (PS) in the circulation was determined, and disappearance curves fitted to a gamma function “multiple hit” model.Mean PS was shorthened to 143,2 ± 47h (normal 232<17); the dissappearance curves were exponential in all but the two patients who had PS within normal limits. The surgically removed aneurysms were dissected and radioactivity of different layers measured. In-111-activity was confined to the superficial layers of the aneurysm.These techniques allow quantitative studies of the in vivo distribution of labelled platelets. Platelets are deposited in the aneurysms, this shortens PS, the disappearance curves become exponential, and the major sites of deposition of In-111-activity are in the liver and spleen. This indicates that although platelets are damaged and deposited in the aneurysm, the reticuloendothelial system remains a major site of platelet sequestration.


1981 ◽  
Author(s):  
A duP Heyns ◽  
P N Badenhorst ◽  
M G Lötter ◽  
F de Kock ◽  
C Herbst ◽  
...  

Kinetics and quantification of the sites of destruction of In-111-oxine labelled autologous platelets was investigated in eight patients with idiopathic thrombocytopenic purpura. The mean platelet count was 17 9 × 109/l; platelets were separated by differential centrifugation and labelled with 5,6 ±2,5 MBq In-111. Whole body and organ In-111-platelet distribution was quantitated with a scintillation camera and a computer assisted imaging system acquisition matrix. Areas of interest were selected with the computer and organ In-111-radioactivity expressed as a percentage of whole body activity. Mean platelet survival was 49,5+29,6h, and the survival curves exponential. Equilibrium percentage organ In-111-radioactivity was (normal values in parenthesis): spleen 33,7±8,8 (31,1 ± 10,2); liver 16,1 ± 9,5 (13,1 ± 1,3); thorax 22,8 ± 3,7 (28,8 ± 5,6). Percentage organ In-111-activity at the time when labelled platelets had been removed from the circulation was: spleen 44,5 ± 16,4 (40 ± 16); liver 16,0 ± 11,5 (32,4 ± 7,2); thorax 19,7±6,0 (17,7 ± 10,3). Thorax activity corresponds to radioactivity in the bony cage of the thorax. Three patterns of platelet sequestration were evident. Three patients had mainly splenic sequestration; two, mainly hepatic sequestration; and three, diffuse reticuloendothelial system sequestration with a major component of platelets destroyed in the bone marrow. Splenectomy was performed in two patients. The pattern of In-111-platelet sequestration was not predictive of response to glucocorticoid therapy or indicative of the necessity for splenectomy. Quantitative In-111-labelled autologous platelet kinetic studies provide a new tool for the investigation of platelet disorders.


Blood ◽  
1989 ◽  
Vol 73 (5) ◽  
pp. 1123-1129 ◽  
Author(s):  
EM Cramer ◽  
N Debili ◽  
JF Martin ◽  
AM Gladwin ◽  
J Breton-Gorius ◽  
...  

Abstract The localization of three known alpha-granule proteins, thrombospondin (TSP), von Willebrand factor (vWF), and fibrinogen (Fg) has been studied in human megakaryocytes (MK) by immunofluorescence and immunoelectron microscopy. For this study, highly purified populations of MK were prepared from human bone marrow either by counterflow centrifugal elutriation or by cell culture from normal subjects and from two patients with megakaryoblastic leukemia. In normal bone marrow immature MK, TSP, and vWF were observed in the Golgi-associated vesicles and in small immature alpha-granules; in mature MK, they were found in the matrix of the mature large alpha-granules. Surprisingly, Fg was detected neither in the Golgi area, nor in the small precursors of alpha-granules; it was only found in the mature alpha-granules but this labeling was generally weaker than in blood platelets. In order to confirm these differences between the expression of Fg and vWF or TSP additional studies were performed on cultured maturing MK: immunofluorescent and ultrastructural immunogold labeling confirmed that vWF appeared early in the maturation while the same immature MK were negative for Fg. In the late maturation stage, the three proteins were detected in the alpha-granules. In order to know whether Fg was lately synthesized or endocytosed from the outside medium, normal MK were grown in the presence of either normal or afibrinogenemic plasma, and normal serum. Fg was detected only in the alpha-granules of MK grown in normal plasma. Similar results were observed with malignant MK, whose maturation was independent of the culture conditions. In conclusion, this study brings immunocytochemical evidence that vWF and TSP are synthesized by immature MK, whereas Fg appears later in the MK alpha-granules and its expression is dependent of the presence of an exogenous Fg source.


Blood ◽  
1989 ◽  
Vol 73 (5) ◽  
pp. 1123-1129 ◽  
Author(s):  
EM Cramer ◽  
N Debili ◽  
JF Martin ◽  
AM Gladwin ◽  
J Breton-Gorius ◽  
...  

The localization of three known alpha-granule proteins, thrombospondin (TSP), von Willebrand factor (vWF), and fibrinogen (Fg) has been studied in human megakaryocytes (MK) by immunofluorescence and immunoelectron microscopy. For this study, highly purified populations of MK were prepared from human bone marrow either by counterflow centrifugal elutriation or by cell culture from normal subjects and from two patients with megakaryoblastic leukemia. In normal bone marrow immature MK, TSP, and vWF were observed in the Golgi-associated vesicles and in small immature alpha-granules; in mature MK, they were found in the matrix of the mature large alpha-granules. Surprisingly, Fg was detected neither in the Golgi area, nor in the small precursors of alpha-granules; it was only found in the mature alpha-granules but this labeling was generally weaker than in blood platelets. In order to confirm these differences between the expression of Fg and vWF or TSP additional studies were performed on cultured maturing MK: immunofluorescent and ultrastructural immunogold labeling confirmed that vWF appeared early in the maturation while the same immature MK were negative for Fg. In the late maturation stage, the three proteins were detected in the alpha-granules. In order to know whether Fg was lately synthesized or endocytosed from the outside medium, normal MK were grown in the presence of either normal or afibrinogenemic plasma, and normal serum. Fg was detected only in the alpha-granules of MK grown in normal plasma. Similar results were observed with malignant MK, whose maturation was independent of the culture conditions. In conclusion, this study brings immunocytochemical evidence that vWF and TSP are synthesized by immature MK, whereas Fg appears later in the MK alpha-granules and its expression is dependent of the presence of an exogenous Fg source.


1985 ◽  
Vol 53 (03) ◽  
pp. 408-410 ◽  
Author(s):  
H F Kotzé ◽  
M G Lötter ◽  
P N Badenhorst ◽  
A du P Heyns

SummaryThe kinetics and sites of sequestration of a fully representative population of In-111-platelets were determined in 11 baboons. The in vivo method of quantification with computer assisted scintillation camera image analysis was validated by sacrificing 5 baboons and measuring and comparing the distribution of organ radioactivity. Recovery of platelets in the circulation was 87% ±7, and their mean survival time was 147 hr± 15. The mean splenic platelet pool was 16.0% ± 1.9. At equilibrium 15.8% ± 2.9 of the In-111-platelets were in the hepatic blood pool. Senescent platelets were destroyed in the reticulo-endothelial system. The major sites of sequestration were: liver (37.6% ±6.0), and the spleen (23.3% ±4.6). The bone marrow sequestrated 14.4% ± 1.7 of the labelled platelets, and 15.5% ±4.0 were present in various other tissues. We conclude that the in vivo method of In-111- quantification is accurate. Senescent platelets are mainly sequestrated in the reticuloendothelial tissue, with the liver, spleen and the bone marrow important sites of sequestration.


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