Enhancement of Tumor Contrast on Radioimmunoscans by Using Mixtures of Monoclonal Antibody F(ab’)2 Fragments

1986 ◽  
Vol 25 (06) ◽  
pp. 216-219 ◽  
Author(s):  
A. Alavi ◽  
H. Koprowski ◽  
D. Herlyn ◽  
D. L. Munz

F(ab’)2 fragments of MAbs GA 73-3 (IgG 2a) and CO 29.11 (IgG 1), which detect distinct antigenic determinants on adenocarcinoma cells of the gastrointestinal tract, were labeled with 131I using the iodogen method. 41 nude mice bearing SW-948 CRC tumors were injected either with a mixture of 100 ¼Ci (11 ¼g) each (n = 9) of the two 131l-F(ab’)2 fragments or with either fragment alone at various doses (each group consisting of 8 mice): GA 73-3,100 ¼Ci (11 ¼g) and 200 ¼Ci (25 ¼g); CO 29.11,100 ¼Ci (11 ¼g) and 200 ¼Ci (26 ¼g). Whole-body images of the mice were obtained daily for up to six days after injection. Ratios of cpm/pixel in the tumor to those in the rest of the body (rob), representing tumor contrast, were significantly (p <0.05) higher in the group of mice injected with the mixture (3.9 ± 1.5) as compared to those given 100 or 200 jiCi of either fragment separately. The biological half-life (T1/2 biol) of the mixture (44.7 ± 14.5 h) in the CRC tumors was significantly (p <0.05) longer than T1/2 biol determined in the groups given either fragment alone. Tv bioL in the rob was similar in all groups of mice examined.

2021 ◽  
Vol 11 (4) ◽  
pp. 1667
Author(s):  
Kerstin Klaser ◽  
Pedro Borges ◽  
Richard Shaw ◽  
Marta Ranzini ◽  
Marc Modat ◽  
...  

Synthesising computed tomography (CT) images from magnetic resonance images (MRI) plays an important role in the field of medical image analysis, both for quantification and diagnostic purposes. Convolutional neural networks (CNNs) have achieved state-of-the-art results in image-to-image translation for brain applications. However, synthesising whole-body images remains largely uncharted territory, involving many challenges, including large image size and limited field of view, complex spatial context, and anatomical differences between images acquired at different times. We propose the use of an uncertainty-aware multi-channel multi-resolution 3D cascade network specifically aiming for whole-body MR to CT synthesis. The Mean Absolute Error on the synthetic CT generated with the MultiResunc network (73.90 HU) is compared to multiple baseline CNNs like 3D U-Net (92.89 HU), HighRes3DNet (89.05 HU) and deep boosted regression (77.58 HU) and shows superior synthesis performance. We ultimately exploit the extrapolation properties of the MultiRes networks on sub-regions of the body.


2001 ◽  
Vol 20 (12) ◽  
pp. 601-609 ◽  
Author(s):  
D Newton ◽  
R J Talbot ◽  
N D Priest

A healthy male volunteer received an intravenous injection of 207Bi as citrate. Levels of the tracer in blood and in excretion samples, and its retention and distribution within the body, were investigated by appropriate radioactivity measurements. Levels in blood fell very rapidly, with only 1% of the injection remaining at 7 h and only ca. 0.1% at 18 days. There was rapid initial excretion, with 55% lost during the first 47 h, principally in urine; however, longer-term losses were much slower and 0.6% remained in the body at 924 days, when the contemporary rate of loss implied a half-life of 1.9 years. Integration of the retention pattern suggested that steady exposure to bismuth compounds could lead ultimately to a body content of 24 times the daily systemic uptake. The largest organ deposit was in the liver, which after 3 days contained ca. 60% of the contemporary whole body content, consistent with reports of hepatotoxicity. These findings differ markedly from the metabolic model for bismuth proposed by the International Commission on Radiological Protection, which envisages a terminal half-life in the body of only 5 days and kidney as the site of highest deposition.


2011 ◽  
Vol 26 (S2) ◽  
pp. 935-935
Author(s):  
R. Krishnadas ◽  
A. Nicol ◽  
S. Champion ◽  
S. Pimlott ◽  
J. Stehouwer ◽  
...  

Levels of serotonin in the body are regulated by the serotonin transporters (SERT), which are predominantly located on the presynaptic terminals of serotonin-containing neurons. Alterations in the density of SERT have been implicated in the pathophysiology of many neuropsychiatric disorders.AimTo evaluate 123-I mZIENT (2(S)-[(S)-2b-carbomethoxy-3b-[3′-((Z)-2-iodoethenyl)phenyl]nortropane), a novel radiopharmaceutical for imaging SERT. The bio-distribution of the radiopharmaceutical in humans was investigated and dosimetry performed.MethodsThe study includes three healthy volunteers and three patients receiving SSRIs. Whole body images obtained on a gamma camera at 10 minutes, 1, 2, 3, 6, 24 and 48 hours post administration. Dosimetry was performed. ROIs were drawn over the brain, heart, kidneys, liver, lungs, salivary glands, spleen, thyroid and intestines. Blood was sampled at 5, 15, & 30 minutes and 1, 2, 3, 6, 24 and 48 hours post administration. Urine was collected at 1, 2, 3, 4, 6, 24 and 48 hours. Brain SPECT images were obtained using a neuroSPECT scanner at 4 hours, evaluated visually and analysed using ROI analysis.ResultsHigh quality SPECT images can be obtained after 100–150 MBq 123-ImZEINT. Regional brain uptake was observed in midbrain and basal ganglia in healthy volunteers, consistent with the known distribution of SERT. Biodistribution images demonstrated highest uptake in the lungs, brain, liver and intestines. The effective dose was within range of other commonly used ligands and is acceptable for clinical imaging.Conclusion123-ImZIENT is a promising agent for imaging SERT in humans with acceptable dosimetry.


1971 ◽  
Vol 51 (4) ◽  
pp. 727-733 ◽  
Author(s):  
W. TAYLOR ◽  
D. E. WRIGHT

SUMMARY [7α-3H]Progesterone was administered to two groups of mice. The localization of radioactivity in tissues was examined by autoradiography and by liquid scintillation counting. Particular attention was paid to the distribution of radioactivity in the liver and biliary system. The greatest amount of administered steroid was taken up by the liver, rapidly secreted into the biliary system and excreted into the gastrointestinal tract. Other tissues, including the uterus, did not take up any appreciable amount of radioactivity, and the autoradiographs showed that radioactivity was not associated with any particular region of hepatic and other cells. The biological half-life of radioactivity in the blood was 11 min in animals given labelled progesterone intravenously.


1971 ◽  
Vol 26 (1) ◽  
pp. 13-20 ◽  
Author(s):  
H. C. Heinrich ◽  
E. E. Gabbe ◽  
D. H. Whang

At delivery commercial 59Fe-preparations contain up to 1% contamination by 60Co, 65Zn, 54Mn, 46Sc, 134Cs, etc., so that the physical half-life of such preparations is not constant and starts to increase permanently after about 100 days. Anion exchange chromatography was used to prepare 59Fe with a radiochemical purity of ≧ 99.999999% as demonstrated by analytical anion exchange chromatography, paper- and thin-layer chromatography, and γ-spectroscopy. The physical half-life of radiochemically pure 59Fe was found to be constant over 500 days with 44.52 ± 0.016 days (λ= 0.015568 ± 0.0000056 [d-1]).The whole-body retention of radiochemically pure 59Fe was measured in man over one year with a 4 π-geometry whole-body radioactivity detector and utilized for the estimation of the effective half-life of 59Fe. The correct physical half-life of radiochemically pure 59Fe was used for the calculation of the biological half-life. Normal male subjects showed an effective half-life of 43.6 ± 0.34 days and a biological half-life of 2136 ± 807 days. This means a whole-body-59Fe-turnover rate of 0.032 ± 0.012%/d equivalent to 1.25 ± 0.46 mg Fe/d (for a whole-body iron pool of 3850 mg in a 70 kg man). Menstruating females were observed to have effective half-lives of 43.1 ± 0.22 days and therefore biological half-lives of 1389 ± 224 days. Their whole-body-59Fe-turnover rate is higher (than in males) with 0.050 ± 0.008%/d. For an optimal whole-body iron pool of 3300 mg (in 60 kg female) this would mean an iron loss of 1.65 ± 0.26 mg/d. Non-menstruating females were quite similar to males. They showed effective and biological 59Fe-half-lives of 43.5 ± 0.48 and 1833 ± 857 days, respectively. Their whole-body-59Fe-turnover rate was calculated to be 0.038 ± 0.018%/d or 1.25 ± 0.59 mg Fe/d (60 kg female with 3300 mg Fe-pool). These experimental data are the first direct and reliable proof for the magnitude of daily iron loss and iron requirements in man.


1993 ◽  
Vol 70 (03) ◽  
pp. 458-464 ◽  
Author(s):  
Mads Krogsgaard Thomsen ◽  
Viggo Diness ◽  
Povl Nilsson ◽  
Søren Nørgaard Rasmussen ◽  
Trevor Taylor ◽  
...  

SummaryRecombinant human factor VII a (rFVIIa) is an activated coagulation factor for intravenous use as a haemostatic agent in haemophiliacs who generate antibodies against factor VIII or IX. Plasma kinetic studies are important for the understanding of the action of rFVIIa which is exerted in the vascular compartment of the body, more specifically on the vessel walls at the site of injury. In the present study, rats were dosed 100 or 500 μg/kg 125I-rFVIIa i. V., without any side effects being observed, and the plasma profile of rFVIIa was studied by 3 different assays that were shown to correlate well at early times post-dose: trichloroacetic acid (TCA)-precipitable drug-related radioactivity, rFVIIa antigen determination by ELISA technique, and the assay of clot activity which is the only clinically applicable assay. The plasma concentration curve could be resolved into 1-3 exponentials, depending on the FVIIa detection principle that was employed. Initially, there was a short (ca. 10 min) phase of increasing concentrations before the attainment of C max. This was followed by a plasma recovery (C max × plasma volume/dose) in the vicinity of one half of the administered dose. The initial volume of distribution (V 1) corresponded to the vascular compartment whereas the volume of distribution at steady state (V ss) was somewhat larger. Whole body clearance (CL-B) of rFVIIa was approx. 1 ml/min per kg, and mean residence time (MRT) and the half-life assumed to be associated with the loss of biological activity was approx. 1 h and 20-45 min, respectively. From these plasma data, rFVIIa appears to be a low clearance compound with limited tissue distribution and a short half-life. Tissue distribution studies showed that high 125I levels, assumed to be rFVIIa-related, included mineralised bone and well-perfused organs such as the liver which suggested that this organ was responsible for a major proportion of CL-B. Finally, mass balance studies showed that almost 90% of the administered radioactivity could be accounted for following an i. v. dose, predominantly as non drug-related radioactivity, even though a small amount of TCA-precipitable radioactivity was excreted via the biliary route. In conclusion, dose- or sex-dependent plasma kinetics and tissue distribution within a dose range of 100 to 500 μg/kg of rFVIIa was not observed. In the early and pharmacologically relevant phase after rFVIIa administration there appears to be good agreement between the various plasma assays employed in the study, indicating that the clot assay yields useful information in studies of rFVIIa plasma pharmacokinetics.


1964 ◽  
Vol 19 (11) ◽  
pp. 1032-1042 ◽  
Author(s):  
H. C. Heinrich ◽  
E. E. Gabbe

Chromatographically pure, vitamin B12-free 60CoCl2 as well as 60Co-vitamin B12 (60Co-cyanocobalamin and 60Co-aquocobalamin) and 60Co-vitamin B12-coenzyme (60Co-5.6-dimethylbenzimidazol-C5′-deoxyadenosyl-cobamid) were given orally and by injection in smallest amounts (10 — 100 pMol = 0.59-5.9 ng Co2®, 100 pMol = 136 ng vitamin B12 and 100 pMol = 158 ng vitamin B12-coenzyme) to female Sprague-Dawley rats.The whole body retention and excretion of the 60Co label was measured in a large volume radioactivity detector with liquid organic scintillators and 4 π-geometry. The biological half life and whole body metabolic turnover rate were calculated for the inorganic and organic cobalt from the kinetics of the 60Co whole body retention.After oral application of 100 pMol 60Co2® nearly all the 60Co is excreted already after 2 days within the faeces (90%), and the urine (15%). Only about 0.9% of the 60Co2⊕ leaves the rats with a biological half life of 18 days. After intramuscular injection of 100 pMol 60Co2⊕ about 91% of the 60Co are excreted in the urine and 10% in the faeces within four weeks. Only 4.6% of the 60Co2⊕ were eliminated with a biological half life of 28 days. The intramuscular injection of only 10 pMol 60Co2⊕ resulted in a faecal excretion of 82%, and an urinary excretion of 21% of the 60Co. A biological half life of 23 days was calculated for 8.6% of the 60Co2⊕. Inorganic cobalt is therefore practically not retained in the body and rapidly excreted mainly with the urine after injection and mainly within the faeces after oral uptake.In contrast to the inorganic cobalt a completely different metabolic behaviour is typical for the cobalt, which is incorporated in the organic structure of the vitamin B12- and vitamin B12-coenzyme molecules. This organic cobalt accumulates in the storage organs and tissues (kidney, liver etc.) after absorption as well as after injection of 100 pMol 60Co-vitamin B12 and 60Co-vitamin B12coenzyme. Only 15% of the 60Co-cyanocobalamin and 9—10% of the 60Co-aquocobalamin and 60°Covitamin B12-coenzyme are excreted within 48 hours after injection. The organ and tissue incorporated 60Co-vitamin B12 and 60Co-vitamin B12-coenzyme is metabolized with a biological half life of about 52 days. From the whole body pool size of 20 μg vitamin B12 and the biological half life a metabolic turnover rate of 0.27 μg vitamin B12/day or 1.34% of the vitamin-B12-pool per days was calculated for the whole body of the rat.The lacking organ and tissue retention of absorbed and injected 60Co2⊕ and its short biological half life in rats (if compared with the organic cobalt in the vitamin B12-structure) as well as the comparison of the total cobalt content of human liver (measured by physical techniques) with the cobalt content calculated from the vitamin B12-content of human liver (measured by microbiological assay) do not support a biological significance and function of inorganic cobalt in mammals. There is no evidence at the moment that any cobalt besides the cobalt in the vitamin B12 and vitamin B12-coenzymes is existing and biochemically active in humans or animals.


2018 ◽  
Vol 18 (07) ◽  
pp. 1840019
Author(s):  
CHAO-HSUN CHUANG ◽  
CHIH-FENG CHEN ◽  
NENG-CHUNG TSENG ◽  
KUANG-LI CHAN ◽  
LUNG-FA PAN ◽  
...  

The biokinetic model of Ga-67 evolution was elaborated in this study for the case-control group of canine liver carcinoma via in-vivo gamma camera/8-slice CT technique. One liver carcinoma dog and two normal dogs were anesthetized with the further whole body scanning by a gamma camera to acquire the time-dependent Ga-67 concentration variations among eight compartments, namely: 1. body fluid, 2. liver, 3. GI Tract, 4. kidney, 5. heart, 6. remainder, 7. bladder, and 8. excretion. Each compartment was assumed to have a unique biological half-life and to be connected to other ones. The initial simplification of assigned compartments was performed based on the general-purpose biokinetic model recommended by the ICRP-30 report. Each object/dog underwent eight scans within 72[Formula: see text]h. The time-dependent empirical data were normalized to the maximal counts/pixel/sec and then integrated with the theoretical estimates, in order to optimize the correlations among compartments. A self-developed program run in MATLAB was used to reflect the actual performance acquired from the gamma camera scanning, while the dimensionless agreement (AT) was applied to assess the discrepancies between empirical and theoretical results. An AT of zero implies a perfect agreement between the theoretical and empirical results, while AT under 20 indicates an excellent consistency between the optimal computational and empirical data, whereas a wide fluctuation of the obtained ATs in the range of 7%–60% corresponded to a medium range of data disagreement in this study. The liver carcinoma dog has revealed a longer biological half-life than normal dogs in the limited range (40 versus 35 or 15[Formula: see text]h). However, the quantified data for other compartments and branching ratios among compartments provided a quite robust substantiation for constructing the biokinetic model of Ga-67 being administrated in the canine hepatic survey.


2016 ◽  
Vol 310 (9) ◽  
pp. G645-G658 ◽  
Author(s):  
Audren Fournel ◽  
Alysson Marlin ◽  
Anne Abot ◽  
Charles Pasquio ◽  
Carla Cirillo ◽  
...  

The gastrointestinal tract is an important interface of exchange between ingested food and the body. Glucose is one of the major dietary sources of energy. All along the gastrointestinal tube, e.g., the oral cavity, small intestine, pancreas, and portal vein, specialized cells referred to as glucosensors detect variations in glucose levels. In response to this glucose detection, these cells send hormonal and neuronal messages to tissues involved in glucose metabolism to regulate glycemia. The gastrointestinal tract continuously communicates with the brain, especially with the hypothalamus, via the gut-brain axis. It is now well established that the cross talk between the gut and the brain is of crucial importance in the control of glucose homeostasis. In addition to receiving glucosensing information from the gut, the hypothalamus may also directly sense glucose. Indeed, the hypothalamus contains glucose-sensitive cells that regulate glucose homeostasis by sending signals to peripheral tissues via the autonomous nervous system. This review summarizes the mechanisms by which glucosensors along the gastrointestinal tract detect glucose, as well as the results of such detection in the whole body, including the hypothalamus. We also highlight how disturbances in the glucosensing process may lead to metabolic disorders such as type 2 diabetes. A better understanding of the pathways regulating glucose homeostasis will further facilitate the development of novel therapeutic strategies for the treatment of metabolic diseases.


1964 ◽  
Vol 04 (02) ◽  
pp. 193-199
Author(s):  
Leopoldo José Anghileri

SummaryA method of preparation of Hg203-labelled 3-chloromercuri-2-methoxypropylurea is given. At the same time the solvent to be used in the chromatographic assay of its radioactive purity is indicated.The absorption and excretion of this compound was studied in rats.A maximum of activity was observed in the kidneys during the first six hours. Subsequently the activity in the kidneys decreased whereas it increased in the intestine. After the first week, the biological half life for the whole body was 8 days and for the kidneys approximately 28 days.A high percentage of the activity in the kidneys was ionic mercury.


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