Aptamers: a novel class of radiopharmaceutical with diagnostic and therapeutic potential

Guhlke, Stefan; Famulok, Michael; Biersack, H.-J.

doi:10.1007/s00259-003-1346-3

Cited by 6 publications

(5 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In summary, the EpCAM aptamers studied, as chemical antibodies, possess a number of superior attributes over monoclonal EpCAM antibodies in terms of tumor penetration, accumulation and retention. Consistent with the criteria of an ideal in vivo imaging agent 44 , 45 , the EpCAM aptamer displays a rapid tumor uptake at around 10 min followed by a rapid clearance. This parameter suggests that the EpCAM aptamers used in this study could be used as an attractive alternative to monoclonal antibodies for in vivo imaging for imaging tumors using radioactive tracers.…”

Section: Discussionmentioning

confidence: 56%

“…In sharp contrast, the signal for antibody observed in tumor sites had a slow onset, with the maximum uptake reached at 3 h. The signal in the tumor receiving EpCAM antibody lasted for at least 6 h. Thus, the aptamer achieved highest concentration in the tumor within 10 min and the signal in the tumor diminished at least 4.5-times faster than that of the antibody. Such quick onset of the maximum signal at the site of the tumor followed by rapid disappearance confers aptamer with highly desirable characteristics for function as a promising molecular imaging probe which outperform antibodies 44 , 45 .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Superior Performance of Aptamer in Tumor Penetration over Antibody: Implication of Aptamer-Based Theranostics in Solid Tumors

Xiang¹,

Zheng²,

Zhou³

et al. 2015

Theranostics

159

109

View full text Add to dashboard Cite

Insufficient penetration of therapeutic agents into tumor tissues results in inadequate drug distribution and lower intracellular concentration of drugs, leading to the increase of drug resistance and resultant failure of cancer treatment. Targeted drug delivery to solid tumors followed by complete drug penetration and durable retention will significantly improve clinical outcomes of cancer therapy. Monoclonal antibodies have been commonly used in clinic for cancer treatment, but their limitation of penetrating into tumor tissues still remains because of their large size. Aptamers, as “chemical antibodies”, are 15-20 times smaller than antibodies. To explore whether aptamers are superior to antibodies in terms of tumor penetration, we carried out the first comprehensive study to compare the performance of an EpCAM aptamer with an EpCAM antibody in theranostic applications. Penetration and retention were studied in in vitro three-dimensional tumorspheres, in vivo live animal imaging and mouse colorectal cancer xenograft model. We found that the EpCAM aptamer can not only effectively penetrate into the tumorsphere cores but can also be retained by tumor sphere cells for at least 24 h, while limited tumor penetration by EpCAM antibody was observed after 4 h incubation. As observed from in vivo live animal imaging, EpCAM aptamers displayed a maximum tumor uptake at around 10 min followed by a rapid clearance after 80 min, while the signal of peak uptake and disappearance of antibody appeared at 3 h and 6 h after intravenous injection, respectively. The signal of PEGylated EpCAM aptamers in xenograft tumors was sustained for 26 h, which was 4.3-fold longer than that of the EpCAM antibody. Consistently, there were 1.67-fold and 6.6-fold higher accumulation of PEGylated aptamer in xenograft tumors than that of antibody, at 3 h and 24 h after intravenous administration, respectively. In addition, the aptamer achieved at least a 4-time better tumor penetration in xenograft tumors than that of the antibody at a 200 μm distances from the blood vessels 3 h after intravenous injection. Taken together, these data indicate that aptmers are superior to antibodies in cancer theranostics due to their better tumor penetration, more homogeneous distribution and longer retention in tumor sites. Thus, aptamers are promising agents for targeted tumor therapeutics and molecular imaging.

show abstract

Section: Discussionmentioning

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Superior Performance of Aptamer in Tumor Penetration over Antibody: Implication of Aptamer-Based Theranostics in Solid Tumors

Xiang¹,

Zheng²,

Zhou³

et al. 2015

Theranostics

159

109

View full text Add to dashboard Cite

show abstract

“…An expanding view is emerging on how oligonucleotides may be used commercially as therapeutic and diagnostic agents. [33][34][35][36][37][38][39][40][41] We recently applied RNA in vitro selection to the discovery of RNA sequences that catalyze solid-state inorganic reactions. In that work, RNA sequences were found that mediate the formation of metal-metal bonds, resulting in the rapid and shapecontrolled synthesis of Pd nanoparticles (RNA "Pdases").…”

Section: Introductionmentioning

confidence: 99%

“…Numerous examples of oligonucleotide (RNA or DNA) sequences are now known that bind to small molecules − and protein targets. − Reactions now known to be catalyzed by oligonucleotides include forming amide carbon−nitrogen, urea carbon−nitrogen, Diels−Alder carbon−carbon, Aldol carbon−carbon, Michael carbon−carbon, and alkylation/substitution. , The discovery of these aptamer and ribozyme sequences has enhanced our fundamental understanding of oligonucleotide structure−function relationships. An expanding view is emerging on how oligonucleotides may be used commercially as therapeutic and diagnostic agents. − …”

Section: Introductionmentioning

confidence: 99%

RNA-Mediated Synthesis of Palladium Nanoparticles on Au Surfaces

Liu

Gugliotti

et al. 2006

Langmuir

View full text Add to dashboard Cite

RNA catalysts for the shape-controlled synthesis of Pd particles from the precursor complex trisdibenzylideneacetone dipalladium ([Pd2(DBA)3] were recently discovered in our laboratory (J. Am. Chem. Soc. 2005, 127, 17814-17818). In the work described here, RNA codes for hexagonal Pd platelets and Pd cubes were covalently immobilized on gold surfaces and evaluated for their activity toward particle synthesis. When coupled to gold via oligoethylene glycol linkers, both RNA sequences were able to catalyze the formation of Pd particles with the same shape control previously observed in solution. For low surface coverages, the average distance between RNA molecules on the surface was estimated at ca. 300 nm, yet large (e.g., dimensions of hundreds of nanometers) Pd hexagons and cubes still formed. This surprising result suggests that a single RNA molecule may be sufficient for nucleating and controlling the shapes of these particles. Finally, the use of surface-bound RNA as a tool for directing the orthogonal synthesis of materials on surfaces was demonstrated. Patterning the RNA code for Pd hexagons next to the code for Pd cubes, followed by incubation in a solution containing [Pd2(DBA)3], resulted in the spontaneous formation of spatially distinct spots of hexagonal and cubic particles.

show abstract

“…One promising approach is the production of receptor binding molecules based on specific nucleic acid sequences that are capable of recognising a wide array of target molecules. These oligonuclide ligands are known as aptamers [35,36]. The term aptamer is derived form the Latin word “aptus” meaning “to fit”.…”

Section: Future Prospectsmentioning

confidence: 99%

In vivo molecular targeted radiotherapy

Perkins

2005

Biomed. Imaging Interv. J.

View full text Add to dashboard Cite

Unsealed radionuclides have been in clinical therapeutic use for well over half a century. Following the early inappropriate clinical administrations of radium salts in the early 20th century, the first real clinical benefits became evident with the use of 131I-sodium iodide for the treatment of hypothyroidism and differentiated thyroid carcinoma and 32P-sodium phosphate for the treatment of polycythaemia vera. In recent years the use of bone seeking agents 89Sr, 153Sm and 186Re for the palliation of bone pain have become widespread and considerable progress has been evident with the use of 131I-MIBG and 90Y-somatostatin receptor binding agents. Although the use of monoclonal antibody based therapeutic products has been slow to evolve, the start of the 21st century has witnessed the first licensed therapeutic antibody conjugates based on 90Y and 131I for the treatment of non-Hodgkin's lymphoma. The future clinical utility of this form of therapy will depend upon the development of radiopharmaceutical conjugates capable of selective binding to molecular targets. The availability of some therapeutic radionuclides such as 188Re produced from the tungsten generator system which can produce activity as required over many months, may make this type of therapy more widely available in some remote and developing countries.Future products will involve cytotoxic radionuclides with appropriate potency, but with physical characteristics that will enable the administration of therapeutic doses with the minimal need for patient isolation. Further developments are likely to involve molecular constructs such as aptamers arising from new developments in biotechnology.Patient trials are still underway and are now examining new methods of administration, dose fractionation and the clinical introduction of alpha emitting radiopharmaceutical conjugates. This review outlines the history, development and future potential of these forms of therapy.

show abstract

Aptamers: a novel class of radiopharmaceutical with diagnostic and therapeutic potential

Cited by 6 publications

References 12 publications

Superior Performance of Aptamer in Tumor Penetration over Antibody: Implication of Aptamer-Based Theranostics in Solid Tumors

Superior Performance of Aptamer in Tumor Penetration over Antibody: Implication of Aptamer-Based Theranostics in Solid Tumors

RNA-Mediated Synthesis of Palladium Nanoparticles on Au Surfaces

In vivo molecular targeted radiotherapy

Contact Info

Product

Resources

About