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Suresh Gupta

Publications and source records attributed to Suresh Gupta.

18 recordsLinked to original sources
PubMed2006

Radiolabeling of MAG3-morpholino oligomers with 188Re at high labeling efficiency and specific radioactivity for tumor pretargeting.

We are investigating a novel pretargeting approach involving an initial IV injection of antitumor antibody conjugated with a phosphorodiamidate morpholino oligomer (MORF, a DNA analog) and the subsequent IV injection of the radiolabeled complement oligomer (cMORF). In this paper, the cMORF was labeled with (188)Re using MAG(3) as chelator for therapeutic applications. Since (c)MORFs are unstable in acidic condition, an optimal labeling pH was first selected and the other labeling factors were then examined. A labeling efficiency of greater than 90% can be achieved even at a concentration of MAG(3)-cMORF as low as 0.8 microM. The labeled cMORF is stable and capable of hybridizing to its complement.

Animals↗
PubMed2006

Novel 3-D structures in polymer films by coupling external and internal fields.

A route to produce novel three-dimensional structures in thin films is demonstrated. Such structures are most difficult to produce in a simple manner without the use of multiple fabrication steps. Here, we show the generation of 3-D cage-type structures using a combination of electrohydrodynamic instabilities and dewetting in a polymer/polymer/air trilayer. Removal of one of the components by use of a selective solvent or by degradation of one of the components reveals the formation of a three-dimensional structure, where one polymer is encased in the other. Thus, by coupling an external field with a surface field inherent to the polymers, a novel fabrication strategy is shown that has clear applications in microfluidics and microelectromechanical systems with extensions to patterned surfaces and structured fluids, like block copolymers.

Journal Article↗
PubMed2006

Surface-functionalized CdSe nanorods for assembly in diblock copolymer templates.

Poly(ethylene oxide)-covered CdSe nanorods were prepared and assembled in diblock copolymer templates by floating the block copolymer templates onto aqueous nanorod solutions. The assembly was enabled by consideration of the surface ligand coverage of the nanorods. Alkane-covered CdSe nanorods prepared by state-of-the-art techniques are not compatible with this assembly process. However, poly(ethylene oxide) (PEO)-functionalized CdSe nanorods were successfully used to assemble the nanorods into the channels and pores of diblock copolymer templates. Other water-dispersible CdSe nanorods, such as those covered with 11-mercaptoundecanoic acid (MUA), did not give the desired assemblies. These results are understood by considering the surface energies of the PEO-covered CdSe nanorods in this interfacial assembly process.

Journal Article↗
PubMed2006

Ion complexation: a route to enhanced block copolymer alignment with electric fields.

We investigate the enhanced alignment of lamellar microdomains under an electric field by addition of lithium chloride (LiCl) into polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) copolymers. A significant increase of dielectric contrast resulting from the formation of lithium-PMMA complexes markedly reduces the critical electric field strength required to overcome the preferential interactions of one block with the substrate, providing a route to achieve the complete alignment of microdomains in block copolymer thin films.

Journal Article↗
PubMed2006

"Self-corralling" nanorods under an applied electric field.

Producing densely packed arrays of nanoscopic anisotropic objects, while necessary for applications in photovoltaic and field emission devices, presents considerable challenges. Here, we present findings on the phase separation of ligand-functionalized nanorods in a polymer matrix under an applied electric field. Densely packed hexagonal arrays of nanorods are produced by this method, where the rods are oriented in the direction of the applied field. Minimization of interfacial energy between the array of nanorods and the surrounding polymer serves to corral the nanorods into the densely packed arrays observed. These findings carry implications toward advancing organic-inorganic heterojunction photovoltaic devices that are expected to benefit from the oriented, densely packed ordered arrays of nanorods produced here.

Cadmium Compounds↗
PubMed2005

Further investigations of morpholino pretargeting in mice--establishing quantitative relations in tumor.

PURPOSE: This laboratory has previously published on phosphorodiamidate morpholino (MORF) pretargeting of tumor in which an anti-tumor antibody conjugated with MORF (a DNA analogue) is first administered, followed at a later time by the radiolabeled complementary MORF (cMORF) as the effector. In the present study, the pharmacokinetics of the antibody and effector were measured under different conditions in mice to establish their quantitative relationships with tumor accumulations by pretargeting. METHODS: A cytosine-free 18 mer cMORF was conjugated with MAG(3) for (99m)Tc labeling while the anti-CEA antibody MN14 was conjugated with DTPA for (111)In labeling and with MORF to impart binding affinity for radiolabeled cMORF. Mice bearing LS174T thigh tumors were used to study: (1) the pharmacokinetics of MN14-MORF by administering (111)In-MN14 at doses between 10 and 100 mug with sacrifice at 2 days and at 30 microg with sacrifice between 1 and 3 days; (2) the biodistribution of (99m)Tc-cMORF following one to four injections (containing 0.15 microg each and separated by 1 h) to animals having received 30 microg of antibody-MORF 2 days earlier and with sacrifice at 3 h after the final injection; and (3) the influence on the biodistribution of (99m)Tc-cMORF of a 2 to 4 day interval between the administration of 30 microg of antibody-MORF and 0.30 microg of (99m)Tc-cMORF. RESULTS: (1) The biodistribution of antibody in percent accumulation (%ID or %ID/g) was largely independent of antibody dose but the absolute accumulation of antibody in tumor increased linearly with dose, showing no evidence of tumor saturation of CEA sites by MN14. Over 1-3 days post antibody administration, blood levels of radiolabeled antibody decreased as expected; however, tumor levels remained constant, thus showing an absence of antibody clearance in tumor over this period. (2) With fixed antibody-MORF dose and increasing number of injections of (99m)Tc-cMORF, cumulative percent blood levels steadily decreased in agreement with the values calculated based on the antibody-MORF in blood. In contrast, cumulative percent tumor levels stayed fairly constant over the first two injections. Thus the antibody-MORF in tumor became saturated with cMORF more slowly than that in blood owing to delivery differences. (3) As expected, percent blood levels decreased with increasing interval between injections of antibody-MORF and (99m)Tc-cMORF. The percent tumor accumulation, however, remained constant over the 3 day interval, thus demonstrating only slow loss of MORF expression in situ. The (99m)Tc-cMORF accumulation in tumor after saturation was mathematically determined based on the antibody-MORF concentration in tumor while the blood levels of (99m)Tc-cMORF were determined based on the concentration of antibody-MORF in blood. CONCLUSION: Contrary to conclusions arrived at in our earlier study, the results of this study show that tumor CEA sites were not saturated even at the highest antibody dose investigated, that accessibility of MORF sites in tumor by (99m)Tc-cMORF was unhindered and that the maximum percent tumor accumulation of (99m)Tc-cMORF depended only on the tumor delivery efficiency of (99m)Tc-cMORF.

Animals↗
PubMed2005

Electric field and dewetting induced hierarchical structure formation in polymer/polymer/air trilayers.

Electrohydrodynamics were studied in a trilayer thin film system consisting of two different polymeric layers and air. A polymer with a higher dielectric constant, poly(methyl methacrylate), was sandwiched between air and a lower dielectric constant polymer, polystyrene. An electric field was applied normal to the interfaces. Along with electrostatic forces, dewetting forces were significant at two of the interfaces, namely, the polystyrene/silicon wafer and the polystyrene/poly(methyl methacrylate) interfaces. These two combined forces produce novel closed-cell structures that are difficult to produce by other existing techniques.

Electromagnetic Fields↗
PubMed2004

Initial observations of 99mTc labelled locked nucleic acids for antisense targeting.

BACKGROUND AND OBJECTIVE: The most recent DNA analogues to become commercially available are known as locked nucleic acids (LNAs). The aim of this study was to evaluate the properties of LNAs for antisense targeting. METHODS: A 15 mer LNA antisense to RIalpha mRNA was studied in cell culture. The antisense LNA (5'-amine linker-TGCCTCCTCACTGGC) was purchased along with its sense control LNA. Surface plasmon resonance was used to compare affinity constants with uniform 18 mer phosphorothioate (PS) DNA and uniform 18 mer phosphodiamidate morpholinos (MORFs, another DNA analogue). After radiolabelling with 99mTc via MAG3, the antisense and sense LNAs were added at 5 nM to wells containing ACHN cells in culture and accumulations measured over 24 h. Subcellular partition was determined after 16 h of incubation by separating membrane bound, cytoplasmic and nuclear fractions. The cell studies were conducted both with naked LNAs and with liposomes (oligofectamine) as carrier. RESULTS: Radiochemical purity was about 95% after purification on a P4 column and each LNA was radiolabelled at about 20 GBq.micromol(-1) (100.microCi.microg(-1)). The surface plasmon resonance results showed a more favourable dissociation constant for the duplex with DNA of the 15 mer LNA (0.55 x 10(-10).M(-1)) compared to the duplex with 18 mer DNA and 18 mer MORFS (2.05 and 1.06 x 10(-10).M(-1), respectively). Because of lower dissociation constants, the hybridization affinities of LNAs are therefore higher than those of uniform and identical PS DNAs or MORFs. The cellular accumulations suggested an antisense effect in that the antisense LNA accumulation was higher than sense both when added naked (1.8% vs. 0.4% at 24 h) and with liposome carrier (3.8% vs. 1.0% at 24 h). Thus while absolute cellular uptake was lower than that observed by this laboratory with other oligomers, the antisense/sense differential was higher. The number of antisense LNAs accumulating per cell specifically (i.e., antisense minus sense) was about 45,000 naked and about 100,000 with carrier. Subcellular partition showed that both LNAs were partitioned to each fraction with antisense accumulations greater than sense and carrier accumulations greater than naked as before. That as much as 2.9% of the antisense LNA (with carrier) was in the cytoplasmic or nuclear factions demonstrates that the LNA was internalized. CONCLUSIONS: LNAs appear to be attractive oligomers for antisense targeting and other radiopharmaceutical applications.

Cell Line↗
PubMed2004

Amplification targeting: a modified pretargeting approach with potential for signal amplification-proof of a concept.

UNLABELLED: Conventional nuclear medicine imaging with large radiolabeled molecules such as antitumor antibodies suffers from slow localization and clearance. Pretargeting is under active investigation as an alternative using either (strept)avidin/biotin, bispecific antibodies, or oligomers. However, only the use of oligomers such as phosphorodiamidate morpholinos (MORFs) in pretargeting offers the potential of signal amplification at the target. Amplification targeting is a multistep procedure with the potential to greatly improve target localization of radioactivity (and eventually drugs) through the intermediate use of polymers conjugated with multiple copies of oligomers. OBJECTIVE: This study was conducted to prove the concept in vivo in tumored mice of amplfication targeting. METHODS: Nude mice bearing LS174T tumors received in order: the anti-CEA antibody MN14 conjugated with MORF, a polymer conjugated with multiple copies of complementary MORFs (cMORFs), and, finally, (99m)Tc-MORF. RESULTS: In tumored animals, dual radiolabels ((99m)Tc and (111)In) were used to demonstrate that, after 18 h, about 25% of antibody MORFs in tumor were targeted with polymeric cMORFs and, after 3 h, about 12% of the polymeric cMORFs in tumor were targeted with (99m)Tc-MORF. Therefore, hybridization in tumor in both cases (i.e., polymeric cMORF to antibody MORF and radiolabeled MORF to polymeric cMORF) was surprisingly efficient given the barriers to targeting in vivo and the competition between targeting and clearance. Moles of radiolabeled MORF accumulating in tumor were more than tripled for study animals receiving all 3 injections compared with control animals not receiving the antibody or the polymer. Furthermore, MORF expression (on antibody) and cMORF expression (on polymer) were rapidly lost in normal organs such as liver, spleen, and kidneys but not in tumor, thus improving the target-to-nontarget ratios. CONCLUSION: Although signal amplification has not yet been convincingly demonstrated and amplification targeting will require further studies for optimization, the concept has now been shown to be feasible.

Animals↗
PubMed2004

Investigations of a (99m)Tc-labeled bacteriophage as a potential infection-specific imaging agent.

UNLABELLED: Because bacteriophages (phages) have a natural specificity for bacteria, it may be possible to develop radiolabeled phages as infection-specific agents. METHODS: The M13 phage was radiolabeled with (99m)Tc via mercaptoacetyltriglycine and purified by polyethylene glycol precipitation. After radiolabeling, the phage was tested for binding at 1, 5, and 10 min to Escherichia coli strain 2537, E. coli strain 25922, and Staphylococcus aureus strain 29213. The radiolabeled phage was also tested for specificity in mouse models that had received a subcutaneous injection of either live (infection/inflammation model) or heat-inactivated (inflammation model) cultures in a thigh. The labeled phage (10(9) plaque-forming units, 1-3.7 MBq) was administered either within 20 min (to minimize the contribution from inflammation) or 3 h after induction. The animals were killed 3 h later. RESULTS: The radiochemical purity of the labeled phage exceeded 95% by strip chromatography using instant thin-layer chromatography/acetone and paper/saline. Binding of the labeled phage to each of the 3 bacterial strains in vitro was immediate, reaching a maximum at 1 min. However, the percentage bound was significantly higher (P = 0.0008) for E. coli 2537 than for either of the other 2 bacteria (84% vs. 41% and 48%). Furthermore, binding to E. coli 2537 was unchanged at 10 min, whereas binding to both E. coli 25922 and S. aureus decreased to 33%. At 3 h in vivo, the ratio of target thigh to normal thigh was significantly higher (P < or = 0.017) in the infection/inflammation model (2 to 2.5 fold) than in the inflammation model (1.5 to 1.8) and therefore suggestive of increased accumulation specific to infection. The difference was slightly more pronounced in animals that received labeled phage at 20 min after inoculation, showing a ratio of 2.3 for infected thigh to normal thigh and a ratio of 1.6 for inflamed thigh to normal thigh. Although absolute uptake was lowest in the infection/inflammation thigh of mice infected with E. coli 2537, this finding was presumably due to the therapeutic effect of the phage on this strain. CONCLUSION: Radiolabeled bacteriophages should be further investigated as potential agents for specific imaging of infection.

Animals↗
PubMed2003

Pretargeting in tumored mice with radiolabeled morpholino oligomer showing low kidney uptake.

We have recently shown that accumulation in mouse kidneys of technetium-99m labeled phosphorodiamidate morpholinos (MORFs) increases with the number of cytosines in the base sequence. To improve tumor/kidney ratios in tumored mice, pretargeting studies were performed with a cytosine-free MORF. An 18-mer MORF (5'-TCTTCTACTTCACAACTA) was conjugated to the anti-CEA antibody MN14 (Immunomedics) and administered to nude mice bearing LS174T tumors. Thereafter, the (99m)Tc-labeled cytosine-free cMORF (5'-TAGTTGTGAAGTAGAAGA-amide-MAG(3)) was administered. For comparison, the identical study was repeated but with our original pair of 18-mer MORFs (5'-GGGTGTACGTCACAACTA-conjugated MN14 and (99m)Tc-labeled 5'-TAGTTGTGACGTACACCC-amide-MAG(3)). Surface plasmon resonance was used to show that the hybridization affinities of the original and the modified pair of MORFs were essentially equal. Hybridization of the cytosine-free cMORF-(99m)Tc to MN14-MORF was demonstrated in vitro by size-exclusion high-performance liquid chromatography. At 3 h, kidney levels in normal mice were 2.0%ID/organ for the modified cMORF vs. 4.1%ID/organ for the original cMORF sequence, while at 24 h, these values were 0.9% vs 1.8%ID/organ. Pretargeting studies in tumored mice receiving 25 microg of conjugated antibody, 0.5 microg of labeled cMORF 48 h later, followed by imaging and sacrifice at 3 h showed that kidney levels were reduced using the cytosine-free cMORF. Moreover, tumor accumulation was about 3.6%ID/g and was independent of sequence. The whole-body images clearly reflected the improved tumor to kidney ratios. By choosing a cytosine-free base sequence for pretargeting studies, kidney accumulation of cMORF-(99m)Tc was reduced without adversely influencing tumor accumulation. The lowering of kidney radioactivity levels in this way may be important to reduce toxicity to this organ in connection with pretargeting radiotherapy studies.

Animals↗
PubMed2003

Disposable diapers: safe and effective.

Nappy rash is a common problem in infants due to their thinner skin, wetness, heat and friction under cloth nappy, fecal enzymes and alkaline urine. The disposable diapers containing Super Absorbent Material (SAM) reduce the incidence of nappy rash. SAM quickly absorbs urine and keeps the skin dry. Also disposable diapers prevent fecal contamination by absorbing the urine and containing stools.

Diaper Rash↗
PubMed2003

Poisoned child: emergency room management.

Poisoning is one of the commonest pediatric emergencies. Most of poisonings in children below 5 years of age, are accidental and fortunately trivial, related to their exploratory nature. However a poisoned child may present as an acute emergency with or without multisystem involvement. The initial phase of management focuses on support of airways, breathing and cardiac function (ABCD of Resuscitation). The second phase includes Evaluation and Detoxification phase. The Evaluation phase involves identification and severity of toxic exposure. Recognizing a Toxidrome (constellation of the signs and symptoms seen with the ingestion of a particular poison) is particularly very helpful when the child presents with an unknown poisoning. Detoxification should proceed simultaneously. The current literature suggests that activated charcoal is the mainstay of GI decontarmination. Whole bowel Irrigation is a new addition to the armamentarium of GI decontamination. At present antidotes are available for few toxins only so the management remains supportive for most poisons.

Charcoal↗
PubMed2003

Current trends in wound management.

Laceration and wound are common emergencies for which children are brought to emergency room. Pediatricians can manage most of these himself. Recently few more methods have become available for wound closure, which are very useful to pediatricians in their office settings. This article stresses on the current trends in wound management. A tidy wound can be repaired primarily while untidy wound requires conversion to tidy wound before closure. Host and environmental factors, which can affect wound healing, should be identified and managed accordingly. Parental presence can be very useful in certain cases. Wound should be examined and irrigated thoroughly to remove foreign bodies and debris. Associated injuries should be assessed and treated appropriately. Suturing, staplers or tissue adhesives can do the wound closure. Last method is particularly useful in pediatric office settings. Antibiotics are needed in certain selected conditions.

Child↗
PubMed2002

Tumor pretargeting in mice using (99m)Tc-labeled morpholino, a DNA analog.

UNLABELLED: Over the past several years, investigators in this laboratory and elsewhere have been studying tumor localization by pretargeting with streptavidin and biotin or with avidin and biotin. Despite encouraging results, difficulties related to endogenous biotin and the immunogenicities of streptavidin and avidin have made a search for alternative strategies sensible. Recently, we have considered the use of DNAs and peptide nucleic acids for this purpose because oligomers can have hybridization affinities equivalent to that of biotin for streptavidin or avidin without the associated difficulties. We now report on the use of a morpholino (MORF), another commercially available synthetic oligomer, for pretargeting applications. MORFs support the nitrogenous bases by nonionic phosphorodiamidate linkages and, besides being nuclease resistant, can display good water solubility. METHODS: An 18mer MORF and its 18mer complementary MORF (cMORF) were obtained with a primary amine through a 3-member alkyl linker on the 3' equivalent end. An anti--carcinoembryonic antigen IgG antibody (MN14) was conjugated with MORF, whereas cMORF was conjugated with N-hydroxysuccinimide-mercaptoacetyltriglycine (MAG3) to permit radiolabeling with (99m)Tc. The biodistribution of labeled cMORF was first evaluated in normal CD-1 mice. Subsequently, nude mice bearing LS174T tumors received 50 microg conjugated antibody 48 h before the administration of 1.0 microg (7.4 MBq) (99m)Tc-MAG3-cMORF. Control animals received the labeled cMORF without prior administration of the antibody. A clearing step was not used. RESULTS: Biodistributions in normal mice showed that (99m)Tc-MAG3-cMORF was excreted rapidly through the kidneys, with only 7 percentage injected dose (%ID) remaining within the whole body (excluding urine) at 3 h. In tumor-bearing mice at 24 h, only 11 %ID of the radioactivity remained in the whole body of study animals, and of this amount, 2 %ID/g was in tumor tissue. The sites with the highest %ID were the kidneys, at 4 %ID/g, and the blood, at 0.5 %ID/g; all other organs had <1 %ID/g. At the same time, values for the control animals were 5 %ID (whole body), 0.05 %ID/g (tumor), and 3 %ID (kidneys). All images reflected high uptake in the tumors and low uptake in the normal tissues of the study mice. CONCLUSION: Pretargeting using MORFs was effective in a mouse tumor model.

Animals↗
PubMedDate not supplied

In vitro and in vivo evaluation of a Technetium-99m-labeled cyclic RGD peptide as a specific marker of alpha(V)beta(3) integrin for tumor imaging.

Three amino acids residues, Arg-Gly-Asp (RGD), in vitronectin and fibronectin show affinity for alpha(V)beta(3) integrins expressed in vascular endothelial cells. That tumor growth can upregulate the expression of these integrins on tumor cells for invasion and metastasis and in tissue neovasculature suggests the potential of developing radiolabeled RGD peptides as antagonists of alpha(V)beta(3) integrins for broad spectrum tumor specific imaging. The polypeptide RGD-4C, which contains four cysteine residues for cyclization, has shown preferential localization on integrins at sites of tumor angiogenesis. Both RGD-4C and RGE (Arg-Gly-Glu)-4C (as control) were purchased and conjugated with 6-hydrazinopyridine-3-carboxylic acid (HYNIC) for 99mTc radiolabeling. After purification of the conjugated peptides by a C18 Sep-Pak cartridge with 20% methanol, both peptides were radiolabeled using tricine. For cell binding studies, both 99mTc peptides were further purified by SE HPLC. High specific radioactivity of labeled cyclized RGD/E (cyclized RGD/E will be simplified as RGD/E through out the text) of about 20 Ci/micromol was achieved. Both 99mTc complexes were stable in the labeling solution for over 24 h at room temperature. In the human umbilical vein endothelial (HUVE) cell studies, the binding at 1 h of radiolabeled RGD/E was determined at 4 degrees C and at concentrations in the picomolar to nanomolar range. Under these conditions, cell accumulation of 99mTc in the case of RGD was as much as 16 times greater than the control RGE. As a check on specificity, 7 nM of native cyclized RGD blocked 50% of the binding of 99mTc-labeled RGD to cells. The binding percentage of 99mTc-labeled RGD to purified alpha(V)beta(3) integrin protein, as determined by SE HPLC, increased with the concentration of the integrin while 99mTc-labeled RGE showed no binding. The association constant for 99mTc-RGD was modest at 7 x 10(6) M(-)(1). In both human renal adenocarcinoma (ACHN) and human colon cancer cell line (LS174T) nude mouse tumor models, the accumulation of 99mTc-labeled RGD/E exhibited no statistical difference. In conclusion, possibly because of limited numbers of alpha(V)beta(3) integrin receptors per tumor cell and low binding affinity, radiolabeled RGD peptides may have limitations as tumor imaging agents.

Adenocarcinoma↗
PubMedDate not supplied

A comparison of in vitro and in vivo stability in mice of two morpholino duplexes differing in chain length.

UNLABELLED: The stability of hybridized duplexes is an important criterion for any radiopharmaceutical application of DNAs or their analogues such as phosphorodiamidate morpholinos (MORFs). OBJECTIVE: The stabilities in vitro and in mice of the duplex between MORF and its complement (cMORF) were investigated for two different chain lengths, a 15-mer MORF compared to the identical MORF but elongated to a 25-mer. METHODS: The hybridization characteristics of the 15-mer MORF with its complementary 15-mer and that of the 25-mer with its complementary 25-mer MORF were measured using surface plasmon resonance (SPR) analysis. For radiolabeling with (99m)Tc, the 15- and 25-mer MORF, both with a primary amine via a 10-member linker on the 3' equivalent end, were conjugated with NHS-MAG(3). The 15- and 25-mer cMORFs were conjugated via their amines to carbodiimidazole treated poly(methyl vinyl ether-alt-maleic acid) (PA) such that about 50 cMORFs were attached to each polymer molecule in both cases (estimated MWs about 300 and 450 kDa, respectively). After hybridization in vitro, both the PA-cMORF15-(99m)Tc-MORF15 and PA-cMORF25-(99m)Tc-MORF25 homoduplexes were evaluated by size exclusion HPLC in saline, after incubation in 37 degrees C serum and in urine obtained 30 min post IV administration to normal mice. Biodistributions were obtained up to 18 h post administration. RESULTS: By SPR, the affinity constants for the homoduplexes were both about 10(9) M(-)(1) with the 25/25 only about 25% higher than the 15/15. However, the affinity constants for the 15/25 and 25/15 heteroduplexes showed a surprisingly 13-fold difference. By HPLC analysis, all duplexes were stable in saline; however, analysis of serum incubates and urine containing PA-cMORF15-(99m)Tc-MORF15 showed an immediate and pronounced low molecular weight peak that was identified by a shift assay to be (99m)Tc-MORF15. The comparable peak in both fluids was much less pronounced in the case of PA-cMORF25-(99m)Tc-MORF25. Whole body radioactivity levels also fell much more rapidly in mice receiving the 15-mer conjugate (65 vs 30% eliminated at 18 h) and biodistribution results showed higher kidney levels for the 15-mer conjugate. Results with the PA-cMORF25-(99m)Tc-MORF15 heteroduplex were more similar to that obtained with the 15-mer homoduplex than the 25-mer homoduplex. CONCLUSION: Despite what is reported to be high hybridization affinities, both the homoduplex and heteroduplexes prepared with (99m)Tc-MORF15 were found to be unstable in serum and in vivo toward dissociation to free (99m)Tc-MORF15. By contrast, homoduplex prepared with (99m)Tc-MORF25 showed higher stability. These differences in hybridization stability may be important considerations in radiopharmaceutical design.

Animals↗