Biomedical subjects

C Song

Publications and source records attributed to C Song.

At least 19 recordsLinked to original sources

PubMed2001

Palladium-imidazolium carbene catalyzed aryl, vinyl, and alkyl Suzuki-Miyaura cross coupling.

[reaction--see text] N,N-Bis-(2,6-diisopropylphenyl)dihydroimidazolium chloride with palladium(II) acetate (2 mol %) was used as catalyst, without added base, to efficiently cross couple aryl, vinyl, and alkyl boronates and boronic acids with aryldiazonium tetrafluoroborate substrates. The reactions were performed at 0 degrees C or rt, giving product in 2 to 4 h with 80 to 90% yields for isolated materials. Diazonium ions, formed in situ, also cross couple under these conditions.

Boranes↗

PubMed2001

Identification and characterization of RA-GEF-2, a Rap guanine nucleotide exchange factor that serves as a downstream target of M-Ras.

The Ras family small GTPase Rap is regulated by an array of specific guanine nucleotide exchange factors (GEFs) in response to upstream stimuli. RA-GEF-1 was identified as a novel Rap GEF, which possesses a Ras/Rap1-associating (RA) domain. Here we report a protein closely related to RA-GEF-1, named RA-GEF-2. Like RA-GEF-1, a putative cyclic nucleotide monophosphate-binding domain, a Ras exchanger motif, a PSD-95/DlgA/ZO-1 domain, and an RA domain in addition to the GEF catalytic domain are found in RA-GEF-2. However, RA-GEF-2 displays a different tissue distribution profile from that of RA-GEF-1. RA-GEF-2 stimulates guanine nucleotide exchange of both Rap1 and Rap2, but not Ha-Ras. The RA domain of RA-GEF-2 binds to M-Ras in a GTP-dependent manner, but not to other Ras family GTPases tested, including Ha-Ras, N-Ras, Rap1A, Rap2A, R-Ras, RalA, Rin, Rit, and Rheb, in contrast to the RA domain of RA-GEF-1, which specifically binds to Rap1. In accordance with this, RA-GEF-2 colocalizes with activated M-Ras in the plasma membrane in COS-7 cells, suggesting a role of RA-GEF-2 in the regulation of Rap1 and Rap2, particularly in the plasma membrane. In fact, an increase in the level of the GTP-bound form of plasma membrane-located Rap1 was observed when coexpressed with RA-GEF-2 and activated M-Ras. Thus, RA-GEF-2 acts as a GEF for Rap1 and Rap2 downstream of M-Ras in the plasma membrane, whereas RA-GEF-1 exerts Rap GEF function in perinuclear compartments including the Golgi apparatus.

Amino Acid Sequence↗

PubMed2001

Protein kinase C epsilon-Src modules direct signal transduction in nitric oxide-induced cardioprotection: complex formation as a means for cardioprotective signaling.

An essential role for protein kinase C epsilon (PKCepsilon) has been shown in multiple forms of cardioprotection; however, there is a distinct paucity of information concerning the signaling architecture that is responsible for the manifestation of a protective phenotype. We and others have recently shown that signal transduction may proceed via the formation of signaling complexes (Circ Res. 2001;88:59-62). In order to understand if the assembly of multiprotein complexes is the manner by which signaling is conducted in cardioprotection, we designed a series of experiments to characterize the associations of Src tyrosine kinase with PKCepsilon in a conscious rabbit model of nitric oxide (NO)-induced late preconditioning. Our data demonstrate that PKCepsilon and Src can form functional signaling modules in vitro: PKCepsilon interacts with Src; the association with PKCepsilon activates Src; and adult cardiac cells receiving recombinant adenoviruses encoding PKCepsilon exhibit increased Src activity. Furthermore, our results show that NO-induced late preconditioning involved PKCepsilon-Src module formation and enhanced the enzymatic activity of PKCepsilon-associated Src. Inhibition of PKC blocked cardioprotection, module formation, and PKCepsilon-associated Src activity, providing direct evidence for a functional role of the PKCepsilon-Src module in the orchestration of NO-induced cardioprotection in conscious rabbits.

Animals↗

PubMed2001

Role of the CDC25 homology domain of phospholipase Cepsilon in amplification of Rap1-dependent signaling.

Phospholipase Cepsilon (PLCepsilon) is a novel class of phosphoinositide-specific PLC characterized by possession of CDC25 homology and Ras/Rap1-associating domains. We and others have shown that human PLCepsilon is translocated from the cytoplasm to the plasma membrane and activated by direct association with Ras at its Ras/Rap1-associating domain. In addition, translocation to the perinuclear region was induced upon association with Rap1.GTP. However, the function of the CDC25 homology domain remains to be clarified. Here we show that the CDC25 homology domain of PLCepsilon functions as a guanine nucleotide exchange factor for Rap1 but not for any other Ras family GTPases examined including Rap2 and Ha-Ras. Consistent with this, coexpression of full-length PLCepsilon or its N-terminal fragment carrying the CDC25 homology domain causes an increase of the intracellular level of Rap1.GTP. Concurrently, stimulation of the downstream kinases B-Raf and extracellular signal-regulated kinase is observed, whereas the intracellular level of Ras.GTP and Raf-1 kinase activity are unaffected. In wild-type Rap1-overexpressing cells, epidermal growth factor induces translocation of PLCepsilon to the perinuclear compartments such as the Golgi apparatus, which is sustained for at least 20 min. In contrast, PLCepsilon lacking the CDC25 domain translocates to the perinuclear compartments only transiently. Further, the formation of Rap1.GTP upon epidermal growth factor stimulation exhibits a prolonged time course in cells expressing full-length PLCepsilon compared with those expressing PLCepsilon lacking the CDC25 homology domain. These results suggest a pivotal role of the CDC25 homology domain in amplifying Rap1-dependent signal transduction, including the activation of PLCepsilon itself, at specific subcellular locations such as the Golgi apparatus.

Animals↗

PubMed2001

Methylenetetrahydrofolate reductase polymorphisms increase risk of esophageal squamous cell carcinoma in a Chinese population.

Methylenetetrahydrofolate reductase (MTHFR) plays a central role in folate metabolism that affects DNA methylation and synthesis. Because germ-line mutations at nucleotides 677 (C-->T) and 1298 (A-->C) in the MTHFR gene cause diminished enzyme activity, and aberrant DNA methylation is oncogenic, we examined the relationship between these two MTHFR polymorphisms and susceptibility to esophageal squamous cell carcinoma (ESCC) in 240 ESCC cases and 360 age- and sex-matched controls in northern CHINA: We found that the allele frequency of MTHFR 677T was significantly higher among cases than among controls (63% versus 41%, P < 0.001). Subjects with the 677TT genotype had a more than 6-fold increased risk of developing ESCC [adjusted odds ratio (OR), 6.18; 95% confidence interval (CI), 3.32-11.51] compared with those who had the 677CC genotype. Furthermore, the elevated ESCC risk associated with the 677 polymorphism was in an allele-dose relationship (trend test, P = 0.0001) with ORs of 1.00, 3.14 (95% CI, 1.94-5.08), and 6.18 (95% CI, 3.32-11.51) for the CC, CT, and TT genotype, respectively, after adjustment for age, sex, smoking status, and the MTHFR 1298 polymorphism. The allele frequency for the MTHFR 1298C was 14% among cases and 17% among controls. The 1298CC genotype was extremely rare in both controls (1.4%) and cases (2.9%) and was also associated with an elevated risk of ESCC (adjusted OR, 4.43; 95% CI, 1.23-16.02) compared with the 1298AA genotype, whereas the 1298AC genotype had no effect on the risk of ESCC. Thus, our findings support the hypothesis that genetic polymorphisms in the MTHFR gene may contribute to susceptibility to carcinogenesis of the esophagus in the at-risk Chinese population.

Alleles↗

PubMed2001

Chronic morphine treatment inhibits oxytocin release from the supraoptic nucleus slices of rats.

Effect of chronic morphine treatment on oxytocin (OT) release from the long term-cultured organotypic slice of the supraoptic nucleus (SON) was investigated using radioimmunoassay. The co-localization of oxytocin and mu-opioid receptor in neurons within the SON was observed with the double-labeled methods of in situ hybridization combined with immunohistochemistry. After exposure to morphine for 6days, the OT levels in culture media were significantly decreased. Naloxone caused much greater release of OT in chronic morphine treatment group than in controls. Naloxone has no effect after acute morphine treatment. 90% of OT-ir (immunoreactive) neurons expressed mu-opioid receptor mRNA in the SON and 45% of the neurons that expressed mu-opioid receptor mRNAs were OT-ir neurons. These results indicated that the neurons within SON could develop dependence on morphine in vitro, and these effects might be exerted via mu-opioid receptor in oxytocin neurons of the SON.

Animals↗

PubMed2001

A putative plant homolog of the yeast beta-1,3-glucan synthase subunit FKS1 from cotton (Gossypium hirsutum L.) fibers.

A novel plant gene CFL1 was cloned from cotton (Gossypium hirsutum L.) fibers by expressed sequence tag (EST) database searching and 5'-RACE (rapid amplification of cDNA ends). This gene shows sequence homology with FKS1 which has been identified as the putative catalytic subunit of the yeast beta-1,3-glucan synthase. It encodes a protein (CFL1p) of 219 kDa with 13 deduced transmembrane helices and 2 large hydrophilic domains, one of which is at the N-terminus and the other in the internal region of the polypeptide. CFL1 displays 21% identity and 41% similarity to FKS1 at the amino acid level over its entire length, with 31% identity and 52% similarity for the hydrophilic central domain. Using RNA and protein blot analysis, CFL1 was found to be expressed at higher levels in cotton fibers during primary wall development. CFL1 also had a strong expression in young roots. Using a calmodulin (CaM)-gel overlay assay, the hydrophilic N-terminal domain of CFL1p was shown to bind to CaM, while the hydrophilic central domain did not. A putative CaM-binding domain, 16 amino acids long, was predicted in the hydrophilic N-terminal domain. Moreover, a product-entrapment assay demonstrated that a protein associated with an in vitro-synthesized callose pellet could be labeled by anti-CFL1 antibodies. Our finding suggests that CFL1 is a putative plant homolog of the yeast beta-1,3-glucan synthase subunit FKS1 and could be involved in callose synthesis.

Calmodulin-Binding Proteins↗

PubMed2001

Auto-oxidized cholesterol sulfates are antagonistic ligands of liver X receptors: implications for the development and treatment of atherosclerosis.

Liver X receptors (LXRs) are members of the nuclear receptor superfamily that are involved in regulation of cholesterol transport and metabolism. Expression of cholesterol 7alpha-hydroxylase, cholesteryl ester transfer protein and certain ATP-binding cassette transporters that are responsible for cholesterol efflux from cells is regulated by LXR and its ligands. In this report we show that 5alpha, 6alpha-epoxycholesterol-3-sulfate (ECHS) and 7-ketocholesterol-3-sulfate inhibit transactivation of a reporter gene by LXR. Non-sulfated forms of these compounds, as well as many other steroid sulfates, had no antagonistic activity. Using chimeric receptors, the antagonistic activity of ECHS was dependent on its interaction with the ligand-binding domain of LXR. ECHS disrupts recruitment of the co-activator Grip 1 into a complex with agonist-bound LXR and this may be responsible for the observed antagonistic properties of these compounds. In various cultured cells, these LXR antagonists also promote de novo cholesterol synthesis and apoptosis. 7-Ketocholesterol and 5alpha, 6alpha-epoxycholesterol are present in blood and have been found in atherosclerotic plaques. If sulfated forms of these oxidized sterols are also present, they may have an important role in foam cell formation by inhibiting LXR function. Since LXR agonists can counteract the activity of these antagonists, they may have therapeutic potential against atherosclerosis.

Arteriosclerosis↗

PubMed2001

Hypolipidemic effects of selective liver X receptor alpha agonists.

Recently, a number of nuclear receptors have been identified as key regulators of cholesterol homeostasis. Two of these, liver X receptor alpha (LXRalpha) (NR1H3) [1] and ubiquitous receptor (UR) (NR1H2) [1], appear to be involved in cholesterol reverse transport and disposal. LXRalpha null gene mice fail to adapt metabolically to high-cholesterol diets. We have recently shown that some 6alpha-hydroxylated bile acid analogs are selective activators of LXRalpha. In this report, we show that these orally administered LXRalpha agonists have an overall hypolipidemic effect in hypercholesterolemic rats, mice and hamsters, which indicates that in these animal models, endogenous LXRalpha agonist is a limiting factor for induction of cholesterol disposal. Furthermore, in animals, these 6alpha-hydroxylated bile acid analogs exhibit a unique pharmacokinetic profile and do not increase the serum triglyceride level; therefore, they may represent a novel class of therapeutic agents for cholesterol management.

Animals↗

PubMed2001

Bisphosphonate derivatized polyurethanes resist calcification.

Calcification of polyurethane cardiovascular implants is an important disease process that has the potential to compromise the long-term function of devices such as polymer heart valves and ventricular assist systems. In this study we report the successful formulation and characterization of bisphosphonate-derivatized polyurethanes, hypothesized to resist implant calcification based on the pharmacologic activity of the immobilized bisphosphonate. Fully polymerized polyurethanes (a polyurea-polyurethane and a polycarbonate polyurethane) were modified (post-polymerization) with bromoalkylation of the hard segments followed by attachment of a bisphosphonate group at the bromine site. These bisphosphonate-polyurethanes resisted calcification in rat 60 day subdermal implants compared to nonmodified control polyurethane implants, that calcify. Bisphosphonates-modified polyurethanes were also studied in circulatory implants using a pulmonary valve cusp replacement model in sheep. Polyurethane cusps modified with bisphosphonate did not calcify in 90 day implants. compared to control polyurethane cusps implants, that demonstrated nodular surface oriented calcific deposits. It is concluded that bisphosphonate modified polyurethanes resist calcification both in subdermal implants and in the circulation. This novel biomaterial approach offers great promise for long-term blood stream implantation with calcification resistance.

Animals↗

PubMed2001

Localized adenovirus gene delivery using antiviral IgG complexation.

Gene therapy with viral vectors has progressed to clinical trials. However, the localization of viral vector delivery to diseased target sites remains a challenge. We tested the hypothesis that an adenoviral vector could be successfully delivered by complexation with a specific antibody that is bound to a biodegradable matrix designed for achieving localized gene transduction. We report the first successful delivery system based upon antibody immobilization of virions in a type I collagen-avidin gel using a polyclonal biotinylated IgG specific for the adenovirus hexon. In vitro stability studies demonstrated retention of viral vector activity with antibody-complexed adenovirus collagen gel preparations, in comparison to loss of vector activity from collagen gels prepared with nonspecific biotinylated IgG. Cell culture investigations using this antibody-controlled release system for adenoviral vector transduction of rat aortic smooth muscle cells (A10) demonstrated a significantly more localized reporter expression (beta-galactosidase) compared with non-antibody-complexed controls. Herpes simplex thymidine kinase (HSVtk) adenoviral vectors were immobilized on avidin-collagen gels via this antibody-complexation approach, and ganciclovir was added to rat smooth muscle cells (A10) in culture with the gels. With complexed HSVtk adenovirus, only cells either in contact with the virus-containing gel or within 50 microm were killed. By comparison, at the same adenovirus and ganciclovir dose, non-antibody-complexed HSVtk adenoviral delivery with ganciclovir resulted in the death of virtually all cells. Myocardial gene transfer studies in pigs demonstrated significantly more efficient right ventricular adenoviral GFP expression with anti-hexon antibody-complexed matrix injections, compared with direct vector injections. Thus, our results show that matrix formulations based on antibody-complexation delivery of adenovirus resulted in site-specific localization of transgene expression that enhances the efficiency of therapeutic vector strategies and provides a potent means for localization, to avoid distal side-effects. This approach has therapeutic potential as an implantable preparation that through the means of antibody-complexation, can localize and optimize viral vector gene therapy.

Adenoviridae↗

PubMed2001

PCR-RFLP genotyping assay for the Bcl I polymorphism of the beta-fibrinogen gene.

Polymorphisms of the beta-fibrinogen gene have been shown to affect plasma fibrinogen levels and risk of coronary artery disease (CAD). We were interested in developing an automated, PCR-based genotyping assay for the purpose of exploring relationships between CAD and CAD-associated aortic stiffness and the Bcl I allele of the beta-fibrinogen gene. We have developed a rapid PCR-RFLP assay for the Bcl I polymorphism of the beta-fibrinogen gene. We carried out direct PCR of genomic DNA to facilitate sequencing of the flanking region of the beta-fibrinogen gene. Using this new sequence information, primers were designed which border the site of the Bcl I polymorphism. One of the primers was labeled with a fluorophore to facilitate detection of the fragments. DNA fragment analysis was carried out using an automated capillary electrophoresis instrument (ABI310). We have developed an improved PCR-RFLP high-sample-throughput assay for the semiautomated detection of the Bcl I polymorphism of the beta-fibrinogen gene. This assay will support screening of large sample sizes required for population studies.

Alleles↗

PubMed2001

Investigation of the influence of keloid-derived keratinocytes on fibroblast growth and proliferation in vitro.

Keloids are disfiguring, proliferative scars that represent a pathological response to cutaneous injury. The overabundant extracellular matrix formation, largely from collagen deposition, is characteristic of these lesions and has led to investigations into the role of the fibroblast in its pathogenesis. Curiously, the role of the epidermis in extracellular matrix collagen deposition of normal skin has been established, but a similar hypothesis in keloids has not been investigated. The aim of this study was to investigate the influence of keloid epithelial keratinocytes on the growth and proliferation of normal fibroblasts in an in vitro serum-free co-culture system. A permeable membrane separated two chambers; the upper chamber contained a fully differentiated stratified epithelium derived from the skin of excised earlobe keloid specimens, whereas the lower chamber contained a monolayer of normal or keloid fibroblasts. Both cell types were nourished by serum-free medium from the lower chamber. Epithelial keratinocytes from five separate earlobe keloid specimens were investigated. Four sets of quadruplicates were performed for each specimen co-cultured with normal fibroblasts or keloid-derived fibroblasts. Controls consisted of (1) normal keratinocytes co-cultured with normal fibroblasts, and (2) fibroblasts grown in serum-free media in the absence of keratinocytes in the upper chamber. Fibroblasts were indirectly quantified by 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay, with results confirmed by DNA content measurement, at days 1 and 5 after the co- culture initiation.Significantly, increased proliferation was seen in fibroblasts co-cultured with keloid keratinocytes, as compared with the normal keratinocyte controls at day 5 (analysis of variance, p < 0.001). These results strongly suggest that the overlying epidermal keratinocytes of the keloid may have an important, previously unappreciated role in keloid pathogenesis using paracrine or epithelial-mesenchymal signaling.

Adolescent↗

PubMed2001

An immediate endothelial cell signaling response to lung ischemia.

Abrupt cessation of lung perfusion induces a rapid endothelial response that is not associated with anoxia but reflects loss of normal shear stress. This response includes membrane depolarization, H(2)O(2) generation, and increased intracellular Ca(2+). We evaluated these parameters immediately upon nonhypoxic ischemia using fluorescence videomicroscopy to image in situ endothelial cells in isolated, ventilated rat lungs. Lungs labeled with 4-(2-[6-(dioctylamino)-2-naphthalenyl]ethenyl)1-(3-sulfopropyl)-pyridinium (di-8-ANEPPS; a membrane potential probe), Amplex Red (an extracellular H(2)O(2) probe), or fluo 3-AM (a Ca(2+) indicator) were subjected to control perfusion followed by global ischemia. Endothelial di-8-ANEPPS fluorescence increased significantly within the first second of ischemia and stabilized at 15 s, indicating membrane depolarization by approximately 17 mV; depolarization was blocked by preperfusion with the K(+) channel agonist lemakalim. Increased H(2)O(2), inhibitable by catalase, was detected in the vascular space at 1-2 s after the onset of ischemia. Increased intracellular Ca(2+) was detected 10-15 s after the onset of ischemia; the initial increase was inhibited by preperfusion with thapsigargin. Thus the temporal sequence of the initial response of endothelial cells in situ to loss of shear stress (i.e., ischemia) is as follows: membrane depolarization, H(2)O(2) release, and increased intracellular Ca(2+).

Animals↗

PubMed2001

Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia.

Chronic hypoxia causes pulmonary hypertension and right ventricular hypertrophy associated with pulmonary vascular remodeling. Because hypoxia might promote generation of oxidative stress in vivo, we hypothesized that oxidative stress may play a role in the hypoxia-induced cardiopulmonary changes and examined the effect of treatment with the antioxidant N-acetylcysteine (NAC) in rats. NAC reduced hypoxia-induced cardiopulmonary alterations at 3 wk of hypoxia. Lung phosphatidylcholine hydroperoxide (PCOOH) increased at days 1 and 7 of the hypoxic exposure, and NAC attenuated the increase in lung PCOOH. Lung xanthine oxidase (XO) activity was elevated from day 1 through day 21, especially during the initial 3 days of the hypoxic exposure. The XO inhibitor allopurinol significantly inhibited the hypoxia-induced increase in lung PCOOH and pulmonary hypertension, and allopurinol treatment only for the initial 3 days also reduced the hypoxia-induced right ventricular hypertrophy and pulmonary vascular thickening. These results suggest that oxidative stress produced by activated XO in the induction phase of hypoxic exposure contributes to the development of chronic hypoxic pulmonary hypertension.

Acetylcysteine↗

PubMed2001

Estimation of the number of polyhydroxyalkanoate (PHA)-degraders in soil and isolation of degraders based on the method of most probable number (MPN) using PHA-film.

A new method to estimate the number of polyhydroxyalkanoates (PHA)-degraders in soil and to isolate degraders, called the film-MPN method, is proposed. The incubation time was measured by the first order reaction (FOR) model. This method was used to estimate numbers of poly(3-hydroxybutyrate-co-3-hydroxyvalerate)[P(3HB-co-3HV)]- and poly(3-hydroxyvalerate-co-4-hydroxybutyrate)[P(3HB-co-4HB)]-degraders in garden soil (4.30 x 10(5) and 2.15 x 10(5) aerobic degraders per gram of dry soil, respectively). The number of P(3HB-co-3HV)-degraders in paddy field soil was 5.06 x 10(5) aerobic degraders per gram dry soil. Also, several P(3HB-co-3HV)-degraders were isolated directly from positive-growth tubes of high dilution.

Biodegradation, Environmental↗

PubMed2001

Production of poly(3-hydroxybutyrateco-3-hydroxyvalerate) from cottonseed oil and valeric acid in batch culture of Raistonia sp. strain JC-64.

A Ralstonia sp. strain JC-64 that is capable of accumulating poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (P[3HB-co-3HV]) from cottonseed oil and valeric acid was isolated. By using a high limiting-nitrogen (HLN) mineral medium as the medium for the second stage of the fermentation process and by adding the two carbon sources at different times, a range of copolymers with 12-62 mol% of 3HV were produced from a series of HLN mineral mediums containing different compositions of cottonseed oil and valeric acid by Ralstonia sp. JC-64. The melting temperature (Tm) of polyhydroxybutyrate from cottonseed oil was 174 degrees C and that of P(3HB-co-3HV) with the highest 3HV-mol fraction (62%) was 81 degrees C.

Carbon↗

PubMed2001

Biodistribution and dosimetry of pretargeted monoclonal antibody 2D12.5 and Y-Janus-DOTA in BALB/c mice with KHJJ mouse adenocarcinoma.

UNLABELLED: Biodistribution and dosimetry of 88Y (and equimolar 90Y) Janus-dodecanetetraacetic acid (DOTA) were performed using a three-step pretargeting protocol in BALB/c mice bearing mouse mammary adenocarcinoma (KHJJ) implants. Pretargeting was performed with mouse monoclonal antibody (mAb) 2D12.5 specific for yttrium-DOTA, and the chase was Y-DOTA-human transferrin conjugate. In this article, we report extensive organ dosimetry and the theoretic limits of the radionuclide physical half-life (T(p)) for pretargeting. METHODS: Organ biodistribution data were obtained from bioassays on tissue taken from tumor mice killed at 3, 24, 48, 72, 96, and 120 h after intravenous injection of 88Y-Janus-DOTA. Uptake and retention of 88Y as a function of time were described by nonlinear least squares fits of the tissue data to multiexponential functions. Radiation dose estimates for equivalent molar amounts of 90Y were subsequently derived from these time-integrated functions. RESULTS: The results were as follows: rapid blood clearance of 88Y-Janus-DOTA; rapid uptake and slow clearance of 88Y-Janus-DOTA from the tumor over 5 d; rapid clearance from all organs and body; largest radiation absorbed dose (AD) per injected dose of 63.52 (cGy/MBq) to tumor; high therapeutic ratios (AD tumor/AD tissue), particularly for blood and bone; and optimal radionuclide T(p) range from 30 min to 10 d. CONCLUSION: Although the absolute concentration of 90Y in the tumor is less using the hapten system than is achieved generally with the chelated radionuclide covalently attached to the mAb, the achievable tumor uptake of radioactivity, coupled with low radioactivity in bone, blood, and other organs, suggests that a three-step pretargeting protocol has considerable promise as a method for 90Y radioimmunotherapy.

Adenocarcinoma↗