A new method for faster blood clearance in radioimmuno-guided surgery

A major inconvenience of intraoperative tumor detection with radiolabeled monoclonal antibody (MoAb) by means of a probe is the long interval needed between the injection of MoAb and surgery (at least 20 days). We describe a new method which entails injection of 125I-labeled biotinylated monoclonal antibodies and cold avidin in order to obtain a rapid blood clearance of the radiotracer. The first clinical application of this protocol has been carried out in a colon cancer patient operated on six days after the administration of 125I-labeled biotinylated MoAb and cold avidin, with an optimal tumor-to-normal tissue ratio and with 90% of the circulating radioactivity cleared in two days.     

Absorption and fate of labelled canthaxanthin 15, 15'-3H2 in rainbow trout (Salmo gairdneri Rich.)

1. Using one force fed meal, absorption of labelled canthaxanthin 15,15'-3H2 was studied by collecting blood via caudal punction at regular intervals and measuring radioactivity in various tissues and organs of rainbow trout. 2. Canthaxanthin absorption showed a large variability between individuals irrespective of their sex. A rapid increase in the radioactivity linked to canthaxanthin 15,15'-3H2 is observed in the blood followed by a slow decrease. 3. Twenty-four and 72 hours after ingestion of labelled canthaxanthin by rainbow trout, the radioactivity was widely distributed. From the total radioactivity given, most was found 24 hours after the meal in the pyloric caeca, ovary and skin. Seventy-two hours after diet, the radioactivity increased in the muscle, liver and kidney. On the other hand, the percentage of radioactivity of intestine and caeca declined. 4. Data from absorption curve indicates that 0.86% of radioactivity ingested is present in the blood, suggesting that canthaxanthin is not readily transferred from the digestive tract. 5. The metabolic clearance of canthaxanthin (lambda = 0.0246/hr +/- 0.005) which would correspond to a half-life of 28 hours gives a preliminary idea of the digestive and metabolic utilization of canthaxanthin by the rainbow trout.     

The incorporation of 35S-heparin into mast cells in the rat and its release into the circulatory bed

It was shown that the intensity of the clearance of 35S-heparin in the blood is extremely high in the first 30 minutes after the introduction of the label. Further on the intensity of the clearance was decreased and by the 60th minute only 11 per cent of the radioactivity was left and by the 240th minute--3.7%. It was established that during intravenous introduction of 35S-heparin the obese cells are capable of accumulating it from the blood flow.     

Intravenous injection of human sex steroid hormone-binding globulin in mouse decreases blood clearance rate and testicular accumulation of orally administered [2-125I]iodobisphenol A

Bisphenol A, an environmental compound with estrogenic activity, has been shown to bind human sex steroid hormone-binding globulin (hSHBG), the main plasma transport protein which regulates the metabolism of androgens and estrogens and limits their access to target organs. The present study was conducted to determine whether physiologically relevant concentrations of hSHBG can influence the blood clearance rate of bisphenol A and its accumulation in the testes. A radioactive [2-125I]iodobisphenol tracer was synthesized with an association constant (Ka) for binding to hSHBG of 0.14 +/- 0.01 x 10(6) M(-1) at 37 degrees C, a value much lower than for [2-125I]iodoestradiol, which was also synthesized. We used i.v. injection of immunopurified hSHBG in adult male mice to maintain hSHBG levels within the physiologically possible range for humans (27-267 nM) before gavage administration of [2-125I]iodobisphenol or [2-125I]iodoestradiol, for measuring the blood clearance rate of radioactive signal in blood samples taken during the following 120 min. Testicular accumulation of radioactivity was measured 24 h and 48 h after gavage of [2-125]iodobisphenol A. In mice receiving immunopurified hSHBG or vehicle, the time-dependent blood clearance of radioactivity exhibited a bi-exponential decrease which indicated alpha-diffusion and beta-elimination phases for both radioactive ligands. The presence of circulating hSHBG significantly and dose-dependently lowered the clearance rate of radioactivity. However, much higher circulating levels of hSHBG were required to retard the blood clearance of [2-125I]iodobisphenol A as compared to those required for [2-125I]iodoestradiol, in keeping with the important difference in their respective Ka value for binding to SHBG. In addition, mice treated with hSHBG exhibited significantly (P = 0.036) reduced testicular accumulation of radioactivity 24 h and 48 h after ingestion of [2-125I]iodobisphenol A. Provided that the binding properties of bisphenol A for hSHBG are not substantially different from those measured for [2-125I]iodobisphenol A, these findings suggest that, although hSHBG binds 2-mono-iodobisphenol A with a relatively low binding affinity, high enough concentrations of circulating hSHBG (range concentrations between 85 and 267 nM) are potentially able to exert a protective effect against exposure to bisphenol A.     

In vivo application of [111In-DTPA-D-Phe1]-octreotide for detection of somatostatin receptor-positive tumors in rats.

Radioiodinated somatostatin analogues are useful ligands for the in vitro and in vivo detection of somatostatin receptors. [111In-DTPA-D-Phe1]-octreotide, a somatostatin analogue labeled with a different radionuclide, also binds specifically to somatostatin receptors in vitro. In this study we investigated its in vivo application in the visualization of somatostatin receptor-positive tumors in rats. The distribution of the radiopharmaceutical was investigated after intravenous injection in normal rats and in rats bearing the somatostatin receptor-positive rat pancreatic carcinoma CA 20948. After injection the radiopharmaceutical was rapidly cleared (50% decrease in maximal blood radioactivity in 4 min), predominantly by the kidneys. Excreted radioactivity was mainly in the form of the intact radiopharmaceutical. Ex vivo autoradiographic studies showed that specific accumulation of radioactivity occurred in somatostatin receptor-containing tissue (anterior pituitary gland). However, in contrast to the adrenals and pituitary, the tracer accumulation in the kidneys was not mediated by somatostatin receptors. Increasing radioactivity over the somatostatin receptor-positive tumors was measured rapidly after injection and the tumors were clearly visualized by gamma camera scintigraphy. In rats pretreated with 1 mg octreotide accumulation of [111In-DTPA-D-Phe1]-octreotide in the tumors was prevented. Because of its relatively long effective half-life, [111In-DTPA-D-Phe1]-octreotide is a radionuclide-coupled somatostatin analogue which can be used to visualize somatostatin receptor-bearing tumors efficiently after 24 hr, when interfering background radioactivity is minimized by renal clearance. This is an advantage over the previously used [123I-Tyr3]-octreotide which has a shorter effective half-life and shows high abdominal interference due to its hepato-biliary clearance. Therefore, [111In-DTPA-D-Phe1]-octreotide seems a better alternative for scintigraphic imaging of somatostatin receptor-bearing tumors.     

Renal uptake and degradation of trapped-label insulin

In order to study the kinetics of insulin degradation in the kidneys and liver, insulin was labelled by a trapped-label procedure and injected into rats. In contrast to conventional 125I-insulin, the trapped-label preparation allows quantitative measurements of the extent of degradation in vivo because the final degradation products do not leave the cells. One hour after injection, the amount of radioactivity in the kidneys from a trace dose of trapped-label insulin was 10 times higher that from conventionally labelled insulin; over 80% of the increase was due to low molecular weight degradation products which were retained in the kidneys. The amount of acid-precipitable radioactivity in the blood was the same for both labelled preparations, indicating that their rates of clearance were similar. In the kidney, we detected no degradation products of molecular weight intermediate between intact insulin and the end products of proteolysis. After 2 h, 33% of the injected dose remained in the kidneys and only 13% in the liver. Over 80% of the renal radioactivity was sedimentable in an isotonic density gradient, indicating that intact insulin, as well as degradation products in the cells, were enclosed within membrane-bound vesicles.     

Quantifying 3H-thymidine incorporation rates by a phylogenetically defined group of marine planktonic bacteria (Bacteriodetes phylum)

The rate of [(3)H-methyl] thymidine ((3)H-TdR) incorporation into DNA has been applied extensively to measure cell production by bacterial communities in aquatic environments. Here we describe a method to quantify (3)H-TdR incorporation by specific, phylogenetically defined members of the bacterial community. The method involves selectively capturing DNA from targeted groups of bacteria and then quantifying its (3)H radioactivity. The method was applied to measure (3)H-TdR incorporation by the members of the phylum Bacteriodetes whose members, which include the Cytophaga-Flavobacter cluster, are ubiquitous in coastal waters. (3)H-labelled DNA from Bacteriodetes was selectively biotinylated in PCR-like reactions that contained a Bacteriodetes-specific 16S rRNA gene primer, thermostable DNA polymerase and biotinylated dUTP. The biotinylated DNA was then captured on streptavidin-coated beads and its (3)H radioactivity determined by scintillation counting. We have termed this method 'selective nucleic acid polymerase-biotinylation and capture' or 'SNAP-BAC'. Internal (33)P-labelled DNA standards were used to quantify the recovery of (3)H-labelled DNA from the SNAP-BAC reactions. The method was verified by successfully targeting Bacteriodetes in simple laboratory mixtures of (3)H-labelled DNA extracted from pure cultures of Bacteriodetes and gamma-proteobacteria. Field application of this method in Puget Sound and off the Washington coast determined that Bacteriodetes were responsible for 56 +/- 17% and 32 +/- 5% of community (3)H-TdR incorporation (1.3 +/- 0.3 and 9.9 +/- 1.7 pmol l(-1) h(-1)) at these two locations.     

Sex dependence of clearance rates of aldosterone and its metabolites from plasma of intact rats.

Following I.V. injection of 3H-aldosterone, the rates of clearance of plasma 3H-radioactivity was demonstrated to be sex-dependent in intact rats. Even though the percentages of CH2Cl2-extractable plasma radioactivity are greater in female than in male rats, the quantities of CH2Cl2-extractable label are similar until 60 min post-injection. However, the quantities of non-extractable, polar metabolites of aldosterone (NEPD) are markedly greater in the plasma of males and rapidly reach peak levels 10 min post-injection of aldosterone. In females, these polar metabolites (NEPD) are rapidly cleared from the blood. After bile-duct cannulation, the rate of excretion of aldosterone radiometabolites was demonstrated to be rapid and sex-dependent. Within 1 hr., female rats excreted via the bile 82% of the injected dose of 3H-aldosterone, compared to 49% in male rats. In both sexes, greater than 95% of the total radioactivity excreted in the bile are non-extractable polar metabolites of aldosterone (NEPD). The sex hormones appear to influence not only the nature of metabolism of aldosterone in the liver, but also the rates of clearance of aldosterone and its metabolites from the plasma into the bile.     

Site-specific conjugation of chain-terminal chelating polymers to Fab' fragments of anti-CEA mAb: effect of linkage type and polymer size on conjugate biodistribution in nude mice bearing human colorectal carcinoma.

Polylysine-based chelating polymers were used for site-specific modification of anti-CEA mAb Fab' fragments via their SH group distal to the antigen-binding site of the antibody molecule. Conjugation was performed using chain-terminal (pyridyldithio)propionate or 4-(p-maleimidophenyl)butyrate moieties to form reducible (S-S) or stable (S-C) bonds between a polymer and Fab' molecule, respectively. One S-S conjugate (S-S9) and two different S-C conjugates (S-C3 and S-C9) were prepared using 3- and 9-kDa molecular weight polymers. No significant loss of immunoreactivity was observed in solid-phase immunoassay, 90-95% of 111In-labeled conjugates being bound to CEA-coated Sepharose beads. After labeling with 111In, the conjugates had a specific radioactivity of 90-120 microCi/micrograms. Injected in nude mice bearing LS 174T carcinoma, the conjugates produced different biodistribution patterns. S-S9 was practically unable to accumulate in tumor and produced very rapid blood clearance of radioactivity and high uptake of radioactivity in liver, spleen, and especially kidneys (225% ID/g 24 h postinjection). S-C3 and S-C9 produced practically the same blood clearances (much slower than that of S-S9) and significant tumor uptake (9-10% ID/g at 24 h). S-C3 gave significantly lower radioactivity in spleen, skin, and bones, and cleared more rapidly from liver and kidneys. Renal uptake for S-C3 and S-C9 was rather high (45% ID/g at 24 h), but much lower than for S-S9.     

Distribution and metabolism of exogenous somatostatin in the rat

The mechanisms of clearance and degradation of injected [3H]somatostatin have been studied in the rat using octadecasilyl-silica extraction and HPLC separation methods.. Three apparent consecutive plasma half-lives of 1, 3 and 20 min were estimated following administration of a pharmacological dose. The initial rapid clearance was due to uptake by various tissue beds, mainly the large peripheral tissue masses muscle, skin and intestine which together accounted for 70% injected radioactivity at 1 min. By contrast the amounts taken up by liver and kidney were relatively small (less than 10%) despite the accumulation of higher concentrations. Massive degradation occurred following uptake and small fragments and amino acids were released into the circulation almost immediately. Inactivation by blood itself was negligible. A slow phase of decline observed at later times suggested a return of intact peptide from extravascular storage sites to sustain plasma concentrations.     

Uptake and processing of human platelet factor 4 by hepatocytes

We previously demonstrated rapid clearance of human platelet factor 4 (PF4) from rabbit and rat blood, its accumulation in the liver, and elimination of PF4 degradation products in urine. The purpose of the present experiments was to characterize interaction of PF4 with cultured rat hepatocytes. 125I-PF4 was taken up by hepatocytes reaching maximum at 180 min. The association of 125I-PF4 with hepatocytes was two times greater at 37 degrees C than at 4 degrees C. At 37 degrees C degradation of 125I-PF4 by hepatocytes was also observed as indicated by the increase of 125I-PF4 radioactivity soluble in 6% trichloroacetic acid. By contrast, no uptake of 125I-beta-thromboglobulin antigen was observed. Autoradiography demonstrated that short incubation (5-20 min) of 125I-PF4 with hepatocytes results in the association of 125I-radioactivity with cell membranes while after longer incubation (60 min) radioactivity was also localized in the endosomes. Heparin inhibited binding and uptake of 125I-PF4 radioactivity by hepatocytes. We propose that part of PF4 released in the circulating blood by activated platelets is bound to the surface of hepatocytes and that it is further processed by these cells.     

Clearance of rat C-reactive protein in vivo and by perfused liver.

The clearance in vivo of rat C-reactive protein (CRP) was studied: (i) in the whole animal and (ii) by using a rat liver perfusion system. Rat CRP is a glycosylated serum protein containing a complex-type biantennary carbohydrate structure on each of its five subunits. The half-life of rat asialo CRP was approximately 5 min. More than 75% of the radioactivity associated with rat asialo CRP and asialo alpha 1-acid glycoprotein (AGP) was recovered in the liver. A small amount of radioactivity (0.8%) associated with rat CRP and rat asialo CRP was found in the lungs. Competitive inhibition of the clearance of 125I-labelled rat asialo CRP from the circulation by asialo AGP was dose dependent, and resulted in a corresponding decrease in the recovery of radioactivity associated with rat asialo CRP in the liver. This indicated that asialo AGP and rat asialo CRP were cleared by the hepatic asialoglycoprotein receptor. This observation was confirmed when the clearance of rat asialo CRP was studied using a rat liver perfusion system. Using this system, the clearance of rat asialo CRP and asialo AGP from the perfusate was inhibited by N-acetylgalactosamine, but not by phosphorylcholine, a ligand through which most of the CRP reactions are mediated. This study provides an example of a circulating serum glycoprotein containing a biantennary carbohydrate structure that is cleared by the asialoglycoprotein receptor.     

The liver is a major organ for clearing simian immunodeficiency virus in rhesus monkeys

Infection with human or simian immunodeficiency virus (SIV) is characterized by the rapid turnover of both viral particles and productively infected cells. It has recently been reported that the clearance of SIV in vivo is exceedingly fast, with half-lives on the order of minutes. The underlying mechanism or site responsible for this rapid clearance, however, remains unknown. To investigate this issue, we chose to infuse infectious SIVmac239 grown from autologous peripheral blood mononuclear cells that were radioactively labeled by [(35)S]methionine and [(35)S]cysteine. This approach eliminates from the viral membrane alloantigens that may have a significant impact on viral clearance. In addition, this approach also permits identification of the sites of viral clearance by measuring the radioactive intensity, even if degradation of SIV RNA occurs in tissues. We now report that the half-life of infused SIV in blood is extremely close to estimates from a previous study, in which unlabeled SIV grown in a heterologous cell line was used. The allogeneic effect due to the presence of human antigens on the surfaces of virions may, therefore, play a minimal role in the high rate of virion clearance. Moreover, close to 30% of infused radioactivity was found in the liver and measureable amounts were detected in the lungs (5.4%), lymph nodes (3.0%), and spleen (0.4%). The detection of a significant proportion of infused virus in the liver suggests that viral clearance from circulation is mediated by a common, nonspecific mechanism, such as the phagocytic functions of the reticuloendothelial system. The rapid clearance and degradation of exogenously infused virions may pose a major obstacle for gene therapy with viral vectors, unless strategies to overcome the rapid in vivo elimination of these particles are developed.     

Targetted localisation and imaging of a murine lymphoma using 131I-labelled monoclonal antibody

In vivo tumor targetting with radiolabelled monoclonal antibodies is a promising approach for the diagnosis and therapy of tumors. A specific monoclonal antibody (mAb), DLAB was generated to the Dalton's lymphoma associated antigen (DLAA) from Haemophilus paragallinarum-induced spontaneous fusion. In order to study the tumor localisation and biodistribution properties of the monoclonal antibody, scintigraphic studies were performed using the radiolabelled DLAB. 131-labelled DLAB was administered intravenously into Swiss mice bearing Dalton's lymphoma and external scintiscanning was performed at different time intervals. Clear tumor images were obtained which revealed selective and specific uptake of radiolabel and the results were compared with biodistribution data. The radioiodinated monoclonal antibody showed fast tumor uptake which increased significantly to 14.6% injected dose (ID)/g at 12 hr post-injection. Enhanced blood clearance of radioactivity resulted in higher tumor/blood ratio of 5.96 at 48 hr. 131I-labelled DLAB resulted in selective and enhanced uptake of the radioactivity by the tumor compared to the non-specific antibody and the results suggest the potential use of spontaneous fusion for producing specific monoclonal antibodies for tumor detection and therapy.     

In situ hybridization for the detection of human parvovirus B19 nucleic acid sequences in paraffin-embedded specimens

Parvovirus infection of pregnant women leading to a transplacentar infection of the fetus may result in hydrops fetalis, and ultimately in intrauterine death of the fetus. In situ hybridization with a biotinylated as well as with a 35S-labeled probe for human parvovirus B19 was performed on formalin-fixed paraffin-embedded (FFPE) tissue from a fetus suffering from non-immunologic hydrops fetalis. Histology was suggestive of viral infection probably with human parvovirus. Parvovirus DNA could be detected and precisely localized mainly in the nuclei of erythroid precursors cells within fetal blood vessels of all organs examined. There was no detection of B19 nucleic acid in parenchymal cells of the placenta or the fetal organs, nor within maternal blood cells. These findings are in agreement with the well-known properties of animal parvoviruses to replicate exclusively in proliferating cells. Taking into consideration the problems in diagnosing human parvovirus infection by light microscopy, we conclude that in situ hybridization with an appropriate non-radioactive probe is a valuable, rapid and safe complementary detection method for the diagnosis and study of human parvovirus infections. The 35S-labeled probe is more sensitive than the biotinylated probe, but has the disadvantages of lower resolution of the signal, longer duration of the assay, the hazard of radioactivity and the shorter shelf-life of the probe.     

Drug-induced perturbations in the in vivo distribution of oncological radiotracers—I. 5-fluoro-6-3H-2′-deoxyuridine influenced by nitrobenzylthioinosine 5′-phosphate (NBMPR-P)

Nitrobenzylthioinosine 5′-monophosphate (NBMPR-P), a water-soluble form of the nucleoside transport inhibitor nitrobenzylthioinosine (NBMPR) was administered by i.v. injection to normal mice and BDF₁ mice with implanted Lewis Lung carcinomas. Tritiated 5-Fluoro-2′-deoxyuridine (³H-FUdR) was injected either alone (control), 10 min before (I + 10), 10 min (I − 10) after, 60 min (I − 60) after, or simultaneously (I = 0) with the transport inhibitor. Tissue distributions of tritium were determined after intervals of 1, 2 and 4 h.The per cent of injected radioactivity (% dose) in liver was increased by all NBMPR-P protocols. Kidney radioactivity was similarly affected, with maximum increases (from 9.3 ± 3.4 to 24.1 ± 5.2% of the injected dose/g) after 1 h in the I − 60 animals. No statistically significant changes in the distribution of radioactivity in tumor, spleen, marrow or blood were induced by doses of NBMPR-P. Elevated levels of tritium radioactivity in blood were accompanied by similar increases in renal and hepatic radioactivity. The apparent increase in the tumor uptake of ³H-FUdR (from 1.4 ± 0.2 to 5.7 ± 2.3% dose/g) was not statistically significant at the 95% confidence limit.In general, NBMPR-P induced a relative tumor-sparing effect and at the same time increased uptake of ³H-FUdR by the liver and kidney, or delayed its clearance from these organs. There was no evidence to suggest that any advantage would be gained by using NBMPR-P treatment in conjunction with radiolabelled FUdR for tumor diagnosis. The data also indicate that the therapeutic ratio for FUdR would be smaller when used with NBMPR-P than when used alone.     

Endometrial blood flow in rats.

The endometrial blood flow was measured in rats by injections of 85Kr saline into aorta and measurements of the clearance of the radioactivity by a Geiger-Müller probe situated in the uterine lumen. Estrus and diestrus were determined by vaginal smears. The endometrial blood flow was found to be 0.88 +/- 0.08 (mean +/- SEM) ml/g tissue/min in estus and 1.60 +/- 0.15 mg/g/min in diestrus. The experiment indicates that the endometrial blood flow and the total uterine blood flow change in opposite directions during the estrous cycle.     

置管溶栓与药物机械溶栓对急性下肢深静脉血栓的临床疗效对比

摘要 目的：对比分析置管溶栓（CDT）与药物机械溶栓（PMT）对急性下肢深静脉血栓（DVT）的安全性与有效性。方法：回顾性分析2018年1月至2021年12月在重庆医科大学附属巴南医院的98例单侧DVT患者临床资料,依据不同的治疗方式分为药物机械溶栓组（PMT组）48例和置管溶栓组（CDT组）50例,对比分析两组患者的围手术期指标、治疗后患侧大腿消肿率和小腿消肿率、血栓溶解率、并发症发生率及术后1年的PTS发生率。结果：PMT组患者的尿激酶使用量及住院时间较CDT组显著缩短,差异具有统计学意义（P<0.05）,但术中出血较CDT组显著增加,差异具有统计学意义（P<0.05）,PMT组患者的患肢消肿率和血栓溶解率显著高于CDT组,差异具有统计学意义（P<0.05）,两组患者的并发症发生率及术后1年的深静脉血栓形成后遗症发生（PTS）率无显著统计学差异（P>0.05）。结论：PMT比CDT具有更好的患肢消肿率及血栓溶解率,且PMT治疗能显著缩短住院时间及减少尿激酶用量,但两者的围手术期并发症发生率及术后1年PTS发生率无显著差异。     

Metabolism and excretion of peptide leukotrienes in the anesthetized rat

The metabolism and excretion of the peptide leukotrienes C4, D4, E4 and N-acetylleukotriene E4 have been studied in the anesthetized rat. The intravenous administration of [3H]leukotriene C4 (2.6 X 10(-11) mol/kg) showed a rapid clearance of radioactivity from the blood and a time-related biliary excretion, recovering 69 +/- 1.6% (n = 6) over 60 min. Less than 1% of total radioactivity was recovered in the urine over the same time period. Similarly, the intravenous administration of [3H]leukotriene D4 (2.5 X 10(-11) mol/kg), [3H]leukotriene E4 (2.5 X 10(-11) mol/kg) and N-acetyl[3H]leukotriene E4 (2.1 X 10(-11) mol/kg) showed a 62 +/- 7.5% (n = 4), 52 +/- 1.5% (n = 4) and 37 +/- 4.6% (n = 5) biliary recovery of radioactivity, respectively, after 60 min. Examination of bile identified leukotriene D4 and N-acetylleukotriene E4 as the main products, although substantial radioactivity, which probably represents unidentified polar products, was present at the solvent fronts of the reverse-phase HPLC. Time course studies indicated a relatively rapid conversion of leukotriene C4 to leukotriene D4, while leukotriene D4 metabolism appeared to be much slower. Leukotriene E4 was a minor product, suggesting that the N-acetylation process is rapid. Incubation of [3H]leukotriene C4 in rat plasma and whole blood in vitro resulted in a slow conversion of leukotriene C4 to leukotriene D4 and leukotriene E4 only. These data suggest that the majority of the leukotriene metabolism and excretion in vivo in the anesthetized rat occurs predominantly in the hepatic system. We conclude that this model is suitable for the measurement of in vivo production of peptide leukotrienes.     

Kinetics of indium-III labelled lymphocytes in normal subjects and patients with Hodgkin's disease.

The distribution in the body and the circulation in the blood of autologous lymphocytes labelled with indium-III were studied in two normal subjects and two patients with Hodgkin''s disease. Four hours after injection radioactivity was identified in the spleen, liver, and bone marrow. Radioactivity, followed by imaging and whole body scanning, began to appear in the lymph nodes four to 18 hours after injection, and some, though not all, lymph node groups in the body could be readily visualised. There were no differences between the normal subjects and the patients with Hodgkin''s disease. The pattern of clearance of radioactivity from the blood was consistent with a normal circulation between blood and lymphoid tissues of the labelled lymphocytes. Since indium-111 stays firmly attached to the cell, it seems an ideal label for studying lymphocyte kinetics, and the use of this technique may have further clinical application.