Modelling radioimmunotherapy with anti-CD45 antibody to obtain a more favourable biodistribution

2009 ◽  
Vol 48 (03) ◽  
pp. 113-119 ◽  
Author(s):  
F. J. Király ◽  
P. Kletting ◽  
S. N. Reske ◽  
G. Glatting
Keyword(s):  
Blood Flow ◽  
Antigen Expression ◽  
Tissue Blood Flow ◽  
Dose Ratio ◽  
Specific Flow ◽  
Blood Flows ◽  
Optimal Delay ◽  
Organ Specific ◽  
Specific Antigens ◽  
Reaction Constants

SummaryRadioimmunotherapy (RIT) is a method to selectively deliver radiation to malignant haemato logical cells by addressing specific antigens. One approach to improve the bio-distribution is to administer a preload of unlabelled antibodies. The aim of this study was to develop a model, which describes distribution of labelled and unlabelled antibodies based on the tissue blood flow and the competing binding behaviour of the antibodies. Such a model can be used to improve biodistribution in the particular case of RIT using anti-CD45 antibodies. Methods: A compartmental model for the interconnected organs was developed. Reaction constants and organ specific flow, antigen concentrations and distribution volumes were taken from the literature. The organ residence times were calculated for different amounts of given labelled and unlabelled antibodies and the time delay between their administrations. Results: The model is capable to describe the preloading effect. The biodistribution of labelled or unlabelled antibodies depends essentially on the specific blood flow to the organ and its antigen expression. The dose ratio of bone marrow to liver is maximized by applying sufficient unlabelled monoclonal antibody (mAb) to saturate antibody binding in the competing organs and by applying the labelled mAb with a delay of more than one hour. Conclusions: The developed model qualitatively describes how a preload can considerably increase selectivity of RIT due to different blood flows and antigen distribution in relevant organs. In addition, simulations can identify the optimal delay between the application of labelled and unlabelled antibody. For future analyses, i.e., to fit patient data, degradation and excretion should be incorporated into the model.

Role of EDRF in the regulation of regional blood flow and vascular resistance at rest and during exercise in conscious dogs

1994 ◽  
Vol 77 (1) ◽  
pp. 165-172 ◽  
Author(s):  
W. Shen ◽  
M. Lundborg ◽  
J. Wang ◽  
J. M. Stewart ◽  
X. Xu ◽  
...  
Keyword(s):  
Blood Flow ◽  
Vascular Resistance ◽  
Skeletal Muscles ◽  
Acute Exercise ◽  
Regional Blood Flow ◽  
Conscious Dogs ◽  
Tissue Blood Flow ◽  
Minor Role ◽  
Blood Flows ◽  
A Minor

The contribution of endothelium-derived relaxing factor (EDRF) to the regulation of regional vascular resistance and tissue blood flow at rest and during acute moderate exercise was studied in chronically instrumented conscious dogs. Radioactive microspheres were injected before and during exercise to measure regional blood flow. An infusion of nitro-L-arginine (L-NA), an analogue of L-arginine, was used to inhibit the synthesis of EDRF and resulted in a significant increase in mean arterial pressure, associated with significantly elevated vascular resistance in heart, skeletal muscle, renal and splanchnic circulations and with decreases in tissue blood flow in those regions at rest. Acute exercise caused a typical redistribution of blood flow, in which there was vasodilation in heart and working skeletal muscles, accompanied by vasoconstriction in kidney and splanchnic circulations. L-NA resulted in significantly elevated vascular resistance during vasodilation in heart and working skeletal muscles and also significantly increased vasoconstriction in renal cortex, stomach, pancreas, liver, and colon during exercise. Blood flows during exercise were largely unaffected by L-NA treatment. Our results suggest that whereas EDRF functions to regulate basal vascular tone and vascular resistance during exercise, EDRF has a minor role in determining the pattern of the redistribution of tissue blood flow during exercise.

scholarly journals Decreased prefrontal oxygenation elicited by stimulation of limb mechanosensitive afferents during cycling exercise

2018 ◽  
Vol 315 (2) ◽  
pp. R230-R240 ◽  
Author(s):  
Ryota Asahara ◽  
Kanji Matsukawa
Keyword(s):  
Blood Flow ◽  
Prefrontal Cortex ◽  
Minute Ventilation ◽  
Peripheral Resistance ◽  
Oxygenation Index ◽  
Tissue Blood Flow ◽  
Doppler Flowmetry ◽  
Blood Flows ◽  
Arterial Blood ◽  
Cutaneous Tissue

Our laboratory reported using near-infrared spectroscopy that feedback from limb mechanoafferents may decrease prefrontal oxygenated-hemoglobin concentration (Oxy-Hb) during the late period of voluntary and passive cycling. To test the hypothesis that the decreased Oxy-Hb of the prefrontal cortex would be augmented depending on the extent of limb mechanoafferent input, the prefrontal Oxy-Hb response was measured during motor-driven one- and two-legged passive cycling for 1 min at various revolutions of pedal movement in 19 subjects. Furthermore, we examined whether calculated tissue oxygenation index (TOI) decreased during passive cycling as the Oxy-Hb did, simultaneously assessing blood flows of extracranial cutaneous tissue and the common and internal carotid arteries (CCA and ICA) with laser and ultrasound Doppler flowmetry. Minute ventilation and cardiac output increased and peripheral resistance decreased during passive cycling, depending on both revolutions of pedal movement and number of limbs, whereas mean arterial blood pressure did not change. Passive cycling did not change end-tidal CO2, suggesting absence of a hypocapnic change. Prefrontal Oxy-Hb decreased during passive cycling, being in proportion to revolution of pedal movement but not number of cycling limbs. In addition, prefrontal TOI decreased during passive cycling as Oxy-Hb did, whereas blood flows of forehead cutaneous tissue, CCA, and ICA did not change significantly. Thus, a decrease in Oxy-Hb reflected a decrease in tissue blood flow of the intracerebral vasculature but not the extracerebral compartment. It is likely that feedback from mechanoafferents decreased regional cerebral blood flow of the prefrontal cortex in relation to the revolutions of pedal movement.

Studies of experimental cervical spinal cord transection

1980 ◽  
Vol 52 (2) ◽  
pp. 197-202 ◽  
Author(s):  
Phillip A. Tibbs ◽  
Byron Young ◽  
Edward P. Todd ◽  
R. G. McAllister ◽  
Steve Hubbard
Keyword(s):  
Blood Flow ◽  
Arterial Pressure ◽  
Myocardial Blood Flow ◽  
Coronary Blood Flow ◽  
Vascular Resistance ◽  
Cervical Cord ◽  
Regional Myocardial Blood Flow ◽  
Tissue Blood Flow ◽  
Coronary Vascular Resistance ◽  
Blood Flows

✓ Effects of cervical cord transection on total and regional myocardial blood flow and coronary vascular resistance were studied in anesthetized dogs using 15-µm microspheres. Left atrial catheters were inserted by thoracotomy in 10 dogs and iodine-125-labeled microspheres were injected to measure baseline tissue blood flows by means of the reference flow technique. Four dogs then underwent laminectomy of the C-6 vertebra (control group), and six underwent laminectomy and cord transection (experimental group). Microspheres labeled with cerium-141, strontium-85, and scandium-46 were injected at 15, 30, and 120 minutes, respectively, after surgical intervention. The dogs were sacrificed, and the radioisotope content of specimens of epicardial, mid-myocardial, and endocardial tissues was determined by differential spectrometry, and tissue blood flow was calculated in relation to arterial reference specimens. No significant differences in baseline endocardial, epicardial, or mid-myocardial blood flow were detected between the control and experimental groups. Tissue blood flows fell significantly in all regions (p < 0.05 or less) at 15, 30, and 120 minutes after transection. No major alteration of the endocardial/epicardial flow ratio occurred, and no electrocardiographic or pathological evidence of ischemia was seen. When corrected for variations in systemic arterial pressure, no differences in coronary vascular resistance between control and cord-transected dogs were observed. These findings suggest that the decreased coronary blood flow following cervical cord transection is secondary to decreased mean arterial pressure rather than to altered coronary vascular resistance. Pharmacological augmentation of perfusion pressure may therefore be necessary to maintain adequate coronary blood flow in patients with acute cord injury who have pre-existent cardiac disease.

Regional distribution of blood flow during mild dynamic leg exercise in the baboon

1983 ◽  
Vol 55 (4) ◽  
pp. 1173-1177 ◽  
Author(s):  
A. R. Hohimer ◽  
J. R. Hales ◽  
L. B. Rowell ◽  
O. A. Smith
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
Cardiac Output ◽  
Muscle Blood Flow ◽  
Regional Distribution ◽  
Tissue Blood Flow ◽  
Blood Flows ◽  
Visceral Organs ◽  
Arterial Blood ◽  
Leg Exercise

Five chair-restrained baboons were trained with operant techniques and a food reward to perform dynamic leg exercise. Cardiac output and blood flows to most tissues were determined by radioactive microsphere distribution. After 2 min of exercise mean arterial blood pressure had increased by 11 +/- 3% (SE), heart rate by 34 +/- 7%, cardiac output by 50 +/- 12%, and O2 consumption by 157 +/- 17%. The blood flow to exercising leg muscle increased by 585 +/- 338% and to the myocardium by 35 +/- 19%. Blood flow to torso and limb skin fell by 38 +/- 4 and 38 +/- 6%, respectively, and similar reductions occurred in adipose tissue blood flow. Nonworking skeletal muscle blood flow decreased by 30 +/- 10%. Renal blood flow was lowered by 16 +/-2%. The lower visceral organs had more variable responses, but when grouped together total splanchnic blood flow fell by 21 +/- 9%. Blood flow to the brain was unchanged with exercise, whereas spinal cord perfusion increased 23 +/- 3%. Thus during short dynamic exercise baboons redistributed blood flow away from skin, fat, nonworking muscles, and visceral organs to supply the needs of exercising muscles. Our data suggest the baboon is a useful animal model for investigating vascular responses of tissues, such as torso skin, adipose, individual visceral organs, and the spinal cord, that cannot be examined in humans.

Joint pressure influences synovial tissue blood flow as determined by colored microspheres

1996 ◽  
Vol 80 (4) ◽  
pp. 1225-1232 ◽  
Author(s):  
J. Hardy ◽  
A. L. Bertone ◽  
W. W. Muir
Keyword(s):  
Blood Flow ◽  
Synovial Tissue ◽  
Synovial Membrane ◽  
Regional Blood Flow ◽  
Joint Capsule ◽  
Joint Disease ◽  
Tissue Blood Flow ◽  
Colored Microspheres ◽  
Blood Flows

We measured regional blood flow in synovial tissue of the antebrachiocarpal, midcarpal, and metacarpophalangeal joints of six normal adult anesthetized horses by using 15-microns-diameter polystyrene colored microspheres. The midcarpal fibrous capsule and synovial membrane blood flows (SMBF) were compared, and the effect of increased intra-articular pressure (30 and 60 mmHg) on midcarpal SMBF was investigated. Dorsal, medial palmar, and lateral palmar midcarpal SMBF measured 108 +/- 36, 61 +/- 12, and 50 +/- 11 microliters.min-1.g-1, respectively. Antebrachiocarpal, dorsal, and palmar metacarpophalangeal SMBF measured 103 +/- 8, 17 +/- 3, and 26 +/- 5 microliters.min-1.g-1, respectively. Midcarpal fibrous joint capsule blood flow was significantly lower than that of the synovial membrane. An increase in midcarpal intra-articular pressure to 30 or 60 mmHg resulted in an 84% decrease in SMBF. Colored microspheres provided a useful technique to determine sequential SMBF. Increased intra-articular pressure significantly altered SMBF, suggesting a role of the regional circulation in the pathogenesis of joint disease.

CNS, CSF, and extradural fluid uptake of various hydrophilic materials in the dogfish

1977 ◽  
Vol 232 (1) ◽  
pp. R45-R53 ◽  
Author(s):  
J. D. Fenstermacher ◽  
C. S. Patlak
Keyword(s):  
Spinal Cord ◽  
Blood Flow ◽  
High Rate ◽  
Tissue Blood Flow ◽  
Distribution Data ◽  
Blood Flows ◽  
Fluid Uptake ◽  
Urea Uptake ◽  
Net Uptake ◽  
Fluid Transfer

The distribution of 10 radioactively labeled materials from blood to CSF, extradural fluid (EDF), telencephalon (cerebrum), medulla, and spinal cord was studied in the dogfish shark. Plasma volumes, blood flows, and blood-to-tissue or fluid-transfer half-times (t1/2) were calculated from these distribution data. Blood-EDF exchange occurred at slow but similar rates for all tracers. Urea uptake by the CSF was very rapid compared to that of the other compounds and may be facilitated by a special mechanism. The tissue plasma spaces of all three CNS regions were small (1.1-1.5%). The calculated rates of tissue blood flow (in ml/g-min) were 0.11 for telencephalon and medulla and 0.055 for spinal cord. Choroid plexus blood flow was estimated to be 2.3 ml/g-min, a surprisingly high rate. Transport between blood and tissue was most rapid for water ethylene glycol and slowest for inulin. The tissue t1/2's of urea indicated that a significant portion of this compound's net uptake by periventricaul brain tissue occurred via the CSF.

Blood flow in normal and dystrophic hamsters during nonshivering thermogenesis

1984 ◽  
Vol 247 (1) ◽  
pp. R189-R195 ◽  
Author(s):  
S. J. Wickler ◽  
B. A. Horwitz
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Cardiac Muscle ◽  
Brown Fat ◽  
Tissue Blood Flow ◽  
Potential Contribution ◽  
Nonshivering Thermogenesis ◽  
Blood Flows ◽  
Brown Adipose

The genetically dystrophic line of hamsters (BIO 14.6) has a significantly reduced capacity for nonshivering thermogenesis (NST) when compared with age-matched normal animals. Of those tissues contributing most to NST, three are altered in the dystrophic hamster (brown fat and cardiac and skeletal muscle). This study has used regional blood flows in response to isoproterenol (a potent stimulator of NST) as a measure of the potential contribution of these tissues to NST. Both isoproterenol-induced O2 consumption and cardiac output were lower in the dystrophic hamsters (13.0 +/- 0.4 vs. 18.2 +/- 0.68 ml O2 X g-0.67 X h-1 and 2.10 +/- 0.10 vs 2.98 +/- 0.16 ml X g-0.67 X min-1, respectively). Tissue blood flow was measured to brown fat, heart, skeletal muscle, liver, kidneys, adrenals, skin, and white fat. Isoproterenol was found to increase blood flows to brown fat, skeletal muscle, and cardiac muscle in normal animals and to brown fat and skeletal muscle in dystrophic hamsters, suggesting that these tissues contribute to NST. However, when corrected for body weight differences, blood flows during isoproterenol infusion to skeletal muscle and to cardiac muscle did not significantly differ between normal and dystrophic animals (2.71 +/- 0.29 vs. 3.33 +/- 0.42 and 2.81 +/- 0.25 vs. 1.85 +/- 0.24 ml X 100 g body wt-1, respectively). In contrast, normal brown adipose tissue had significantly elevated blood flows (3.50 +/- 0.39 vs. 2.28 +/- 0.27 ml X 100 g body wt-1). Thus these observations provide in vivo support for the conclusion that the reduced NST capacity of dystrophic hamsters is due, in large part, to a reduced thermogenic contribution of brown fat.

Tissue-specific extravasation of albumin-bound Evans blue in hypothermic and rewarmed rats

2002 ◽  
Vol 80 (3) ◽  
pp. 233-243 ◽  
Author(s):  
Candace B Matthew ◽  
Ingrid V Sils ◽  
Amy M Bastille
Keyword(s):  
Blood Flow ◽  
Vascular Permeability ◽  
Evans Blue ◽  
Gastrocnemius Muscle ◽  
Endothelial Permeability ◽  
Specific Flow ◽  
Flow Rates ◽  
Decrease Blood Flow ◽  
Organ Specific ◽  
Endothelial Integrity

The effects of hypothermia and rewarming on endothelial integrity were examined in intestines, kidney, heart, gastrocnemius muscle, liver, spleen, and brain by measuring albumin-bound Evans blue loss from the vasculature. Ten groups of twelve rats, normothermic with no pentobarbital, normothermic sampled at 2, 3, or 4 h after pentobarbital, hypothermic to 20, 25, or 30°C, and rewarmed from 20, 25, or 30°C, were cooled in copper coils through which water circulated. Hypothermic rats were cooled to the desired core temperature and maintained there for 1 h; rewarmed rats were cooled to the same core temperatures, maintained there for 1 h, and then rewarmed. Following Evans blue administration, animals were euthanized with methoxyflurane, tissues removed, and Evans blue extracted. Because hypothermia and rewarming significantly decrease blood flow, organ-specific flow rates for hypothermic and rewarmed tissues were used to predict extravasation. Hypothermia decreased extravasation in tissues with continuous endothelium (brain, muscle) and increased it in tissues with discontinuous endothelium (liver, lung, spleen). All tissues exhibited significant (p < 0.05) differences from normothermic controls. These differences are attributed to a combination of anesthesia, flow, and (or) change in endothelial permeability, suggesting that appropriate choice of organ and temperature would facilitate testing pharmacological means of promoting return to normal perfusion.Key words: hypothermia, rewarming, vascular permeability, Evans blue, endothelium, anesthesia, thermoregulation.

COMPARISON OF ANTIHYPERTENSIVE EFFECT OF MOXONIDINE VERSUS CLONIDINE IN RENAL FAILURE PATIENTS.

2018 ◽  
Vol 6 (9) ◽  
Author(s):  
DR.MATHEW GEORGE ◽  
DR.LINCY JOSEPH ◽  
MRS.DEEPTHI MATHEW ◽  
ALISHA MARIA SHAJI ◽  
BIJI JOSEPH ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Failure ◽  
Blood Flow ◽  
Blood Vessel ◽  
Blood Vessels ◽  
High Blood Pressure ◽  
Antihypertensive Effect ◽  
The Body ◽  
Ability To Work ◽  
Blood Flows

Blood pressure is the force of blood pushing against blood vessel walls as the heart pumps out blood, and high blood pressure, also called hypertension, is an increase in the amount of force that blood places on blood vessels as it moves through the body. Factors that can increase this force include higher blood volume due to extra fluid in the blood and blood vessels that are narrow, stiff, or clogged(1). High blood pressure can damage blood vessels in the kidneys, reducing their ability to work properly. When the force of blood flow is high, blood vessels stretch so blood flows more easily. Eventually, this stretching scars and weakens blood vessels throughout the body, including those in the kidneys.

MEASUREMENT OF BLOOD FLOW WITH FREELY DIFFUSIBLE INDICATORS AS INERT GASES, ANTIPYRINE, LABELLED WATER AND RUBIDIUM

1972 ◽  
Vol 68 (2_Supplb) ◽  
pp. S95-S111 ◽  
Author(s):  
Niels A. Lassen ◽  
Ole Andrée Larsen
Keyword(s):  
Blood Flow ◽  
Flow Measurement ◽  
Capillary Wall ◽  
Inert Gases ◽  
Tissue Blood Flow ◽  
Blood Flow Measurement

ABSTRACT Indicators which freely cross the capillary wall can be used for measurement of tissue blood flow in many different ways. Basically one can distinguish two categories of methods, viz. the ones where the indicator enters the tissue via the inflowing blood and the ones where the indicator is deposited locally in the tissue. The most important methods are briefly described with special emphasis on the theory of blood flow measurement.

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