Effect of concentrate feeding sequence on equine hindgut fermentation parameters

Feeding a diet with a small amount of hay and a high proportion of concentrate given in large meals entails a risk of colic to horses as this can impact the hindgut microbial ecosystem. To counteract this potential negative effect, one feeding strategy is to modify the distribution sequence of concentrate and hay. The purpose of the present study was to assess the impact of feeding the concentrate meal before or with the hay meal on fermentative parameters postprandial variations in caecum and right ventral colon contents and faeces. We focused on the comparison of pH value and volatile fatty acid (VFA) concentrations between the three compartments. Four horses fitted with two cannulas in the caecum and right ventral colon were fed a 100% hay diet (H) for a 3-week period, and then a 40% concentrate–60% hay diet for two consecutive periods of 3 weeks each. Concentrate and hay were offered simultaneously in two equal meals at 0800 and 1700 h (HC1) during one period, or separately in two equal meals at 0800 and 1600 h for the concentrate and at 1000 and 1730 h for hay (HC2) during the second one. During the 2^nd week of each diet period (H, HC1, HC2), caecal, right ventral colonic and faecal samples were collected before (0) and at 2, 4, 6 and 8 h after the morning meal. pH values and VFA concentrations were measured. Adding concentrate to the hay was associated with a decrease of pH value in the caecum, right ventral colon and faeces and an increase of faecal VFA concentrations (P<0.01). An impact of the concentrate feeding sequence was observed on caecal pH and faecal propionate concentration (P<0.001) but none on the other parameters investigated. In the caecum and right ventral colon, pH values decreased and VFA concentrations increased within the range of 4 to 8 h after the morning meal. Our data suggested that the variation of faecal pH could be an indicator of those of the caecal and right ventral colonic pH with a delay of 2 h. The present study showed that hay and commercial pelleted could be safely distributed simultaneously, thus making easier every day horse feeding.     

Synthesis and radiolabeling of 111In-core-cross linked polymeric micelle-octreotide for near-infrared fluoroscopy and single photon emission computed tomography imaging

The objective of this study was the development of a dual-modality imaging device, namely ¹¹¹In-core-cross-linked polymeric micelle (CCPM)-octreotide, for neuroendocrine tumor detection, using near-infrared fluoroscopy (NIRF) and single photon emission computed tomography (SPECT). The tumor targeting ability of the ¹¹¹In-labeled CCPM-octreotide was evaluated in a tumor mouse model. SPECT/CT, NIRF and gamma imaging results showed high tumor uptake of ¹¹¹In-labeled CCPM-octreotide. In contrast, there was a much lower signal in the same mouse model injected with ¹¹¹In-labeled CCPM. The high accumulation of ¹¹¹In-labeled CCPM-octreotide in U87 tumor was reduced after co-injection with an excess amount of CCPM-octreotide. These results suggested CCPM-octreotide’s potential applications in tumor diagnosis, drug delivery and molecular imaging.     

Facile synthesis and evaluation of C-functionalized benzyl-1-oxa-4,7,10-triazacyclododecane-N,N',N″-triacetic acid as chelating agent for ¹¹¹In-labeled polypeptides

A 12-membered polyazamacrocycle, 1-oxa-4,7,10-triazacyclododecane-N,N′,N″-triacetic acid (ODTA), has been reported to provide an indium chelate of net neutral charge with thermodynamic stability higher than 1,4,7,10-tetraazacyclododecane-N,N′,N″,N?-tetraacetic acid (DOTA). However, neither synthetic procedure for a C-functionalized ODTA (C-ODTA) nor its chelating ability with a trace amount of radioactive indium-111 (¹¹¹In) has been elucidated. We herein present a facile synthetic procedure for C-ODTA, and estimated its ability as a chelating agent for radiolabeling peptides and proteins with ¹¹¹In. The synthetic procedure involves the synthesis of a linear precursor using a para-substituted phenylalanine derivative as a starting material. The following intramolecular cyclization reaction was best performed (>73% yield) when Boc-protected linear compound and the condensation reagent, HATU, were simultaneously added to the reaction vessel at the same flow rate. The cyclic compound was then reduced with BH₃ and alkylated with tert-butyl bromoacetate. The synthetic procedure was straightforward and some optimization would be required. However, most of the intermediate compounds were obtained easily in good yields, suggesting that the present synthetic procedure would be useful to synthesize C-ODTA derivatives. The intramolecular cyclization reaction might also be applicable to synthesize polyazamacrocycles of different ring sizes and cyclic peptides. In ¹¹¹In radiolabeling reactions, C-ODTA provided ¹¹¹In chelates in higher radiochemical yields at low ligand concentrations when compared with C-DOTA. The ¹¹¹In-labeled C-ODTA remained unchanged in the presence of apo-transferrin. The biodistribution studies also showed that the ¹¹¹In-labeled compound was mainly excreted into urine as intact. These findings indicate that C-ODTA would be useful to prepare ¹¹¹In-labeled peptides of high specific activities in high radiochemical yields.     

Observations on the use of a cation exchange resin for the preparation of metal-depleted media for lymphocyte culture

A chelating resin specific for divalent cations (Chelex) was used to prepare metal-depleted media for lymphocyte culture. A batch procedure (resin in pH 7.4 phosphate buffer/specimen, 1:1) removed 70-80% of iron, 77-87% of copper and 88-98% of zinc, calcium and magnesium. At variance with other reports, when a resin/specimen ratio of 1:4 was used, iron chelation decreased to 40%, whereas other cation chelation remained unchanged. Best chelation for iron and calcium was obtained at pH 5-6.4; for copper, zinc and magnesium, at pH 7.4-8.0. During the procedure protein content decreased by 8-10%; arginine and lysine by 80%; asparagine, cystine, tyrosine and phenylalanine by 60%, other amino acids by 35%. These new data suggest that cation-depleted media prepared with Chelex may be used to study the effects of cations on lymphocytes in culture, provided that the most appropriate pH and resin/specimen ratio are selected and adequate amino acid replacement is performed. Results on normal human lymphocytes are reported.     

Comparative studies using 125I- and 111In-labeled monoclonal antibodies

HDP-1 monoclonal antibody was labeled with ¹¹¹In using deferoxamine, diethylenetriaminepentaacetic acid or 1-(para-bromoacetamidobenzyl)-EDTA as chelating agents or with ¹²⁵I. The in vitro binding capacity and stability of the labeled molecules were evaluated using affinity chromatography. The biodistribution and imaging capabilities were compared using an animal model system that does not involve the use of tumors. Similar studies were done using the corresponding labeled F(ab′)₂ and Fab′ fragments. All labeled molecules, except those treated with deferoxamine, were stable in vitro. When tested in vivo, all retained their capacity to localize in the target tissue (lung). The lung %ID/g levels for the ¹¹¹In-labeled molecules were, however, slightly lower than those observed for the corresponding ¹²⁵I-labeled molecules. High uptake was also observed in the liver or kidneys when the ¹¹¹In-labeled molecules were used; no such results were obtained with the ¹²⁵I-labeled molecules. More work appears to be necessary before the use of bifunctional chelates becomes the optimal method for radiolabeling monoclonal antibodies for use in tumor imaging.     

Synthesis and evaluation of indium-111-labeled imidazothiadiazole sulfonamide derivative for single photon emission computed tomography imaging targeting carbonic anhydrase-IX

Carbonic anhydrase-IX (CA-IX) is a zinc enzyme overexpressed in the hypoxic regions of many types of solid tumors; therefore, in vivo imaging of CA-IX may contribute to cancer diagnosis. In this study, we newly designed and synthesized an ¹¹¹In-labeled CA-IX imaging agent based on an imidazothiadiazole sulfonamide (IS) scaffold conjugated with a chelating moiety, DO3A ([¹¹¹In]DO3A-IS1), and evaluated its utility for imaging of CA-IX high-expressing tumors. [¹¹¹In]DO3A-IS1 was successfully synthesized at a 76% radiochemical yield by reacting its precursor with ¹¹¹InCl₃ in acetate buffer. In in vitro assays, [¹¹¹In]DO3A-IS1 showed marked stability in murine plasma and greater binding to CA-IX high-expressing (HT-29) cells (118 ± 21% initial dose/mg protein) than CA-IX low-expressing (MDA-MB-231) cells (1.4 ± 0.3% initial dose/mg protein). Moreover, in an in vivo biodistribution assay, [¹¹¹In]DO3A-IS1 showed marked accumulation in the HT-29 tumor (8.71 ± 1.41% injected dose/g at 24 h postinjection). In addition, in a single photon emission computed tomography (SPECT) study, [¹¹¹In]DO3A-IS1 clearly and selectively visualized the HT-29 tumor as compared with the MDA-MB-231 tumor. These results indicate that [¹¹¹In]DO3A-IS1 may serve as a useful SPECT imaging agent with the novel scaffold targeting CA-IX.     

Assessment of antral grinding of a model solid meal with echo-planar imaging

Mathematical modeling of how physical factors alter gastric emptying is limited by lack of precise measures of the forces exerted on gastric contents. We have produced agar gel beads (diameter 1.27 cm) with a range of fracture strengths (0.15-0.90 N) and assessed their breakdown by measuring their half-residence time (RT(1/2)) using magnetic resonance imaging. Beads were ingested either with a high (HV)- or low (LV)-viscosity liquid nutrient meal. With the LV meal, RT(1/2) was similar for bead strengths ranging from 0.15 to 0.65 N but increased from 22 +/- 2 min (bead strength <0.65 N) to 65 +/- 12 min for bead strengths >0.65 N. With the HV meal, emptying of the harder beads was accelerated. The sense of fullness after ingesting the LV meal correlated linearly (correlation coefficient = 0.99) with gastric volume and was independently increased by the harder beads, which were associated with an increased antral diameter. We conclude that the maximum force exerted by the gastric antrum is close to 0.65 N and that gastric sieving is impaired by HV meals.     

Localization of enzymes and alkaloidal metabolites in Papaver latex

In continuing studies on the metabolic activity of Papaver somniferum, latex has been examined for its enzyme and alkaloidal metabolite content. After an initial centrifugation of latex at 1000g, the pellet which contained a heterogeneous population of dense organelles was further resolved on sucrose gradients. Of the enzymes monitored, acid phosphatase and l-3,4-dihydroxyphenylalanine decarboxylase were found to be in the latex 1000g supernatant, whereas catecholase (polyphenolase) was localized in two distinct organelles within the 1000g sediment. The lighter organelles, sedimenting at 30% sucrose, contained a soluble enzyme which was readily released on organelle plasmolysis, whereas the catecholase found within the heavier organelles, sedimenting at 55–60% sucrose, was membrane bound and showed significant activity only in the presence of Triton X-100. These latter organelles also contained the alkaloids, including morphine and thebaine, and were observed to readily accumulate [¹⁴CH₃]morphine. The alkaloid precursor, dopamine, was localized in the same dense vesicle fraction as the alkaloids. The rate of uptake of [7-¹⁴C]dopamine into these fractions at room temperature, however, was markedly lower than that of morphine. Electron microscopic examination of the organelles of various densities revealed that they possessed different morphology. The results are consistent with the concept that both the 1000g and supernatant fractions of the latex are required for alkaloid biosynthesis and that a sub-population of dense organelles found in the 1000g sediment have at least a function as a storage compartment for both alkaloids and their catecholamine precursor.     

Dosimetric parameters of the new design 103Pd brachytherapy source based on Monte Carlo study

In this study version 5 of the MCNP photon transport simulation was used to calculate the dosimetric parameters for new palladium brachytherapy source design following AAPM Task Group No. 43U1 report. The internal source components include four resin beads of 0.6 mm diameters with ¹⁰³Pd uniformly absorbed inside and one cylindrical copper marker with 1.5 mm length. The resin beads and marker are then encapsulated within 0.8 mm in diameter and 4.5 mm long cylindrical capsule of titanium. The dose rate constant, Λ, line and point-source radial dose function, g_L(r) and g_P(r), and the anisotropy function, F(r,θ) of the IR01-¹⁰³Pd seed have been calculated at distances from 0.25 to 5 cm. All the results are in good agreement with previously published thermoluminescence-dosimeter measured values [3] for the source. The dosimetric parameters calculated in this work showed that in dosimetry point of view, the IR01-¹⁰³Pd seed is suitable for use in brachytherapy of prostate cancer.     

Flow rate and bead size as critical parameters for immobilized-yeast reactors

The productivity of immobilized yeast cell reactors varies with a number of parameters, including flow, amount and growth rate of yeast, bead size and type of medium. Variation of these parameters has a pronounced effect on reaction rate. This paper presents typical ranges for these productivities and demonstrates the patterns of changes that take place when bead size, flow and reaction medium are varied. Saccharomyces cerevisiae cells were immobilized in calcium alginate beads for the production of ethanol. The productivity of immobilized yeast in a batch reactor (0.2 g ethanol/g yeast · h) was only two-thirds that of free cells suspended at an equivalent cell density (0.3 g ethanol/g yeast · h). Different flow rates and bead sizes were used to ‘optimize’ the productivity. The productivity of 3.34 mm beads at a flow rate of 8.8 litre h^?1(superficial velocity: 0.12 cm s^?1) was 95% higher than that at 1.0 l h^?1. Maximum productivities of 0.34, 0.27, 0.22 g/g yeast· h were obtained (at a flow rate of 8.8 l h^?1) for 9.2% yeast-immobilized beads of 3.34, 4.45 and 5.65 mm in diameter, respectively.     

Low melting point agarose beads as a standard method for plantlet regeneration from protoplasts within the Cichorium genus

Key message

A standard method has been developed with which we are able to fully regenerate protoplasts of different Cichorium species. For the first time, endive protoplasts have been regenerated into plantlets.

Abstract

Protoplast regeneration is essential for somatic hybridizations. In this study, a standard method for plantlet regeneration from Cichorium protoplasts was developed. We evaluated the effect of the low melting point agarose (LMPA) bead technique on the regeneration capacity of protoplasts of seven C. intybus and four C. endivia genotypes. The LMPA bead technique was more efficient than culture in liquid or solid medium and allowed us to obtain plating efficiencies up to 4.9?% in C. intybus genotypes and efficiencies of up to 0.7?% in C. endivia genotypes. Moreover, the LMPA bead technique offers great advantages over liquid and solid culture systems: the media can be readily refreshed, protoplasts can be monitored separately, and microcalli can easily be removed from the beads. This increased efficiency was observed for all of the 11 Cichorium genotypes tested. Shoot formation was induced more efficiently when using 0.5?mg?l^?1 indole-3-acetic acid-enriched medium (up to 87.5?% of the protoplast-derived calli started shoot development) compared to 1-naphthaleneacetic acid-enriched medium. The LMPA bead technique optimized in this study enabled for the first time the full plantlet regeneration from protoplasts of C. endivia genotypes and increased the protoplast regenerating ability in other Cichorium species. This fine-tuned LMPA bead technique can therefore be applied for protoplast regeneration after protoplast fusions of the genus Cichorium.     

Lithium‐Pretreated Hard Carbon as High‐Performance Sodium‐Ion Battery Anodes

Hard carbon (HC) is the state‐of‐the‐art anode material for sodium‐ion batteries (SIBs). However, its performance has been plagued by the limited initial Coulombic efficiency (ICE) and mediocre rate performance. Here, experimental and theoretical studies are combined to demonstrate the application of lithium‐pretreated HC (LPHC) as high‐performance anode materials for SIBs by manipulating the solid electrolyte interphase in tetraglyme (TEGDME)‐based electrolyte. The LPHC in TEGDME can 1) deliver > 92% ICE and ≈220 mAh g^?1 specific capacity, twice of the capacity (≈100 mAh g^?1) in carbonate electrolyte; 2) achieve > 85% capacity retention over 1000 cycles at 1000 mA g^?1 current density (4 C rate, 1 C = 250 mA g^?1) with a specific capacity of ≈150 mAh g^?1, ≈15 times of the capacity (10 mAh g^?1) in carbonate. The full cell of Na₃V₂(PO₄)₃‐LPHC in TEGDME demonstrated close to theoretical specific capacity of ≈98 mAh g^?1 based on Na₃V₂(PO₄)₃ cathode, ≈2.5 times of the value (≈40 mAh g^?1) with nontreated HC. This work provides new perception on the anode development for SIBs.     

Evaluation of two new bifunctional chelates for radiolabeling a parathyroid-specific monoclonal antibody with In-111

BB5-G1, a monoclonal antibody specific for human parathyroid cell membrane antigen was conjugated with two new ligands, BrMe₂HBED and BrφHBED and radiolabeled with ¹¹¹In. We have compared the biodistribution of ¹¹¹In-labeled BBS using the new ligands to conventionally labeled (¹²⁵I-labeled and ¹¹¹In-DTPA-labeled) BBS in a nude mouse model. Both ¹¹¹In-BrMe₂HBED-BB5 and ¹¹¹In-BrφHBED-BB5 attained high parathyroid-to-blood and parathyroid-to-muscle ratios by 72–96 h. ¹¹¹In-BrφHBED-BB5 showed lower %ID/g than ¹¹¹In-BrMe₂HBED-BB5 in the clearance organs, the liver and kidney; renal activity had cleared significantly by 120 h. This work suggests that ¹¹¹In-BrφHBED-BB5 offers improved in vivo behavior and may be useful as a radiopharmaceutical for localizing parathyroid tissue.     

A comparison of the subcellular distribution of 5′-nucleotidase, (Na+K+)-ATPase and adenyl cyclase in beef thyroid gland

The validity of 5′-nucleotidase as a plasma membrane marker enzyme in beef thyroid has been tested by comparing the subcellular distribution of its activity to that of (Na⁺K⁺)-activated ATPase and adenyl cyclase. The specific activity and total activity of (Na⁺K⁺)-ATPase and adenyl cyclase were greatest in the 1000 × g (“nuclear”) and 33 000 × g (“mitochondrial and lysosomal”) fractions. In contrast, 5′-nucleotidase activity was concentrated in the 165 000 × g (“microsomal”) pellet and supernatant. Partially purified plasma membranes were separated from the 1000 (N₂), 30 000 (M₂) and 165 000 × g (P₂) pellets by discontinuous sucrose gradient centrifugation. Again a discordant distribution of these enzyme activities was observed. (Na⁺K⁺)-ATPase specific activity was increased approximately 30-fold over the homogenate in Fractions N₂ and M₂. Basal, thyroid-stimulating hormone-and fluoride-stimulated adenyl cyclase activities were concentrated in the same fractions. 5′-Nucleotidase activity was preferentially located in M₂ and P₂. These differences in distribution pattern suggest that 5′-nucleotidase activity is not uniquely located in the plasma membrane in the thyroid.     

Refinement of an adherence assay for the measurement of bacterial attachment to silica beads

An in vitro adherence assay [4] which utilised radiolabelled bacteria and silica beads was used to investigate firm and loose attachment of bacteria. A systematic evaluation of the effects of the assay conditions, including incubation vessel, bacteria to bead interaction, bead washing and bead weight, was carried out in an attempt to improve the reproducibility of adherence measurements. Four oral streptococcal strains (S. mutans NCTC 10449, S. sanguis NCTC 7863 and 10904, S. salivarius NCTC 8618) were studied with saliva coated and uncoated silica beads.Using the improved system, total bacterial adherence to uncoated beads was high (45–60% of bacteria present). While saliva coating of beads reduced total and firm adherence of all strains, these reductions were less marked (P > 0.005) for S. sanguis NCTC 10904.     

Culture parameters affecting xylitol production by Debaryomyces hansenii immobilized in alginate beads

Yeast immobilization offers operational advantages such as high cell concentration, and some drawbacks related to cell leaking and restricted mass transfer inside particles. The influence of bead size, chitosan, bead charge, volume of liquid media, and the use of corncob hydrolyzates and vinasses as culture medium were analyzed on xylitol production by Debaryomyces hansenii immobilized in alginate beads. The results showed a profuse growth of free cells, accounting 75–95% of total biomass, but electron micrographs revealed the generation of a dense biofilm with hyphal morphology at the bead surface and a very low intraparticular growth. Xylitol production was not affected by the size of particle; however chitosan had a negative effect. The use of corn cob as carbon source and twofold diluted vinasses as economic nutrients incremented xylitol concentration to 13.7 g L^?1 (Y_P/S = 0.56 g g^?1; Q_P = 0.29 g L^?1 h^?1). The best conditions corresponded to high bead charges and intermediate liquid volumes (44 g Na-alginate and 110 mL liquid medium). These results showed the feasibility of employing these cheap substrates, reflected the importance of the microaerobical conditions, and pointed to the favorable effect of cell immobilization on the metabolism of xylitol production.     

Sucralfate delays gastric emptying of liquids and solids in duodenal ulcer patients

Gastric emptying studies were performed on nine healthy volunteers and ten duodenal ulcer (DU) patients utilizing a dual radionuclide technique to assess simultaneously emptying rates of liquid (¹¹¹In labeled water) and solid (^99mTc sulfur colloid labeled chicken liver) components of a meal. One gram of sucralfate was compared to placebo in separate days in a randomized double-blind crossover fashion. Subjects ingested the radiolabeled test meal 1 h after receiving medication, and gastric emptying was monitored for 3 h using a γ camera interfaced with a computer. We found that DU patients had significantly faster gastric emptying of solids (P < 0.05) compared to normals on the placebo days, while liquid emptying rates were similar. Sucralfate, in the DU patients, significantly (P < 0.05) slowed gastric emptying of water from 20 to 40 min and emptying of the solid component from 100–160 min after the meal compared to placebo. In normal subjects, gastric emptying of liquids and solids was not significantly affected by sucralfate.We conclude that slowing of gastric emptying, possibly mediated through aluminum ions, occurs in DU patients on sucralfate. This may be one mechanism by which sucralfate enhances healing and decreases recurrence of duodenal ulcer.     

Enhancing the value of nitrogen from rapeseed meal for microbial oil production

Rapeseed meal, a major byproduct of biodiesel production, has been used as a low-cost raw material for the production of a generic microbial feedstock through a consolidated bioconversion process. Various strategies were tested for the production of a novel fermentation medium, rich in free amino nitrogen (FAN): commercial enzymes (CEs) (2.7 mg g^?1 dry meal), liquid state fungal pre-treatment (LSF) using Aspergillus oryzae (4.6 mg g^?1), liquid state fungal pre-treatment followed by fungal autolysis (LSFA) (9.13 mg g^?1), liquid state pre-treatment using fungal enzymatic broth (EB) (2.1 mg g^?1), but the best strategy was a solid state fungal pre-treatment followed by fungal autolysis (34.5 mg g^?1).The bioavailability of the nitrogen sources in the novel medium was confirmed in fed-batch bioreactor studies, in which 82.3 g dry cell L^?1 of the oleaginous yeast Rhodosporidium toruloides Y4 was obtained with a lipid content of 48%. The dry cell weight obtained was higher than that obtained using conventional yeast extract, due to a higher total nitrogen content in the novel biomedium. The fatty acids obtained from the microbial oil were similar to those derived from rapeseed oil.     

Woronin bodies fromPenicillium chrysogenum: Isolation and characterization by analytical subcellular fractionation

Differential centrifugation of whole homogenates ofPenicillium chrysogenum, disrupted by a modified Ballotini bead method, resulted in the enrichment of Woronin bodies between 800g (5 minutes) and 6000g (10 minutes). Isolated Woronin bodies are membrane-bounded, electron-opaque, approximately spherical organelles, 0.11 to 0.29 μm in diameter. Woronin bodies have a buoyant density (ϱ) of 1.21 g cm⁻³ and S_20,w values of 6300 to 37,600 in sucrose gradients. Analytical subcellular fractionation of whole homogenates in a zonal rotor showed that Woronin bodies did not cosediment with marker enzymes for lysosomes (acid phosphatase), peroxisomes (catalase), mitochondria (cytochrome c oxidase), or endoplasmic reticulum (NADPH cytochrome c reductase).     

Advantage of residualizing radiolabels for an internalizing antibody against the B-cell lymphoma antigen, CD22

 LL2 is an anti-CD22 pan-B-cell monoclonal antibody which, when radiolabeled, has a high sensitivity for detecting B-cell, non-Hodgkin’s lymphoma (NHL), as well as an antitumor efficacy in therapeutic applications. The aim of this study was to determine whether intracellularly retained radiolabels have an advantage in the diagnosis and therapy of lymphoma with LL2. In vitro studies showed that iodinated LL2 is intracellularly catabolized, with a rapid release of the radioiodine from the cell. In contrast, residualizing radiolabels, such as radioactive metals, are retained intracellularly for substantially longer. In vivo studies were performed using LL2-labeled with radioiodine by a non-residualizing (chloramine-T) or a residualizing method (dilactitol-tyramine, DLT), or with a radioactive metal (¹¹¹In). The biodistribution of a mixture of ¹²⁵I (non-residualizing chloramine-T compared to residualizing DLT), ¹¹¹In-labeled LL2 murine IgG2a or its fragments [F(ab′)₂, Fab′], as well as its humanized, CDR-grafted form, was studied in nude mice bearing the RL human B-cell NHL cell line. Radiation doses were calculated from the biodistribution data according to the Medical International Radiation Dose scheme to assess the potential advantage for therapeutic applications. At all assay times, tumor uptake was higher with the residualizing labels (i.e., ¹¹¹In and DLT-¹²⁵I) than with the non-residualizing iodine label. For example, tumor/blood ratios of ¹¹¹In-labeled IgG were 3.2-, 3.5- and 2.8-fold higher than for non-residualizing iodinated IgG on days 3, 7 and 14, respectively. Similar results were obtained for DLT-labeled IgG and fragments with residualized radiolabels. Tumor/organ ratios also were higher with residualizing labels. No significant differences in tumor, blood and organ uptake were observed between murine and humanized LL2. The conventionally iodinated anti-CD20 antibody, 1F5, had tumor uptake values comparable to those of iodinated LL2, the uptake of both antibodies being strongly dependent on tumor size. These data suggest that, with internalizing antibodies such as LL2, labeling with intracellularly retained isotopes has an advantage over released ones, which justifies further clinical trials with residualizing ¹¹¹In-labeled LL2 for diagnosis, and residualizing ¹³¹I and ⁹⁰Y labels for therapy. Received: 23 August 1996 / Accepted: 7 February 1997