Improved targeting of the αvβ3 integrin by multimerisation of RGD peptides

Dijkgraaf, Ingrid; Kruijtzer, John A. W.; Liu, Shuang; Soede, Annemieke C.; Oyen, Wim J.G.; Corstens, F.H.M.; Liskamp, Rob M. J.; Boerman, Otto C.

doi:10.1007/s00259-006-0180-9

Cited by 201 publications

(286 citation statements)

References 18 publications

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“…Since the v3 binding site is located in a central cleft between the two subunits, the minimum length of a linker between two ligands should be at least of 60Å to allow binding to two adjacent receptors. In most studies with cyclic divalent RGD peptides, the spacer length between the two ligands was much shorter than the length required for binding two contiguous receptors [147][148][149]. Moreover, in a recent study, a dimeric RGD with a spacer compatible in length with a putative attachment of the dimer to two adjacent receptors did not have a stronger affinity than a molecule with a shorter spacer length, or the monomer [150].…”

Section: Multimerization 28mentioning

confidence: 99%

Cell-penetrating and cell-targeting peptides in drug delivery

Vivès

Schmidt

Pèlegrin

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

317

272

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During the last decade, the potential of peptides for drug delivery into cells has been highlighted by the discovery of several cell-penetrating peptides (CPPs). CPPs are very efficient in delivering various molecules into cells. However, except in some specific cases, their lack of cell specificity remains the major drawback for their clinical development. At the same time, various peptides with specific binding activity for a given cell line (cell-targeting peptides) have also been reported in the literature. One of the goals of the next years will be to optimize the tissue and cell delivery of therapeutic molecules by means of peptides which combine both targeting and internalization advantages. In this review, we describe the main strategies that are currently in use or likely to be employed in the near future to associate both targeting and delivery properties.

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Section: Multimerization 28mentioning

confidence: 99%

Cell-penetrating and cell-targeting peptides in drug delivery

Vivès

Schmidt

Pèlegrin

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

317

272

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“…Since the Arg-Gly-Asp (RGD) peptide is specific to α v β 3 (10,11), numerous applications based on the RGD/α v β 3 targeting delivery system have been reported in molecular imaging (12,13). Similarly, the Asn-Gly-Arg (NGR) peptide is a specific recognition sequence of CD 13 (14).…”

Section: Introductionmentioning

confidence: 99%

In vitro assessment of the dual-targeting behavior of a peptide-based magnetic resonance imaging contrast agent

Yang

Zhang

et al. 2013

International Journal of Molecular Medicine

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Abstract. In this study, a peptide-based dual-targeting magnetic resonance imaging (MRI) contrast agent (S8) was designed and synthesized. Arg-Gly-Asp (RGD) and Asn-Gly-Arg (NGR) were combined in the targeting vector so as to allow binding, on the surface of tumor cells, to integrin α v β 3 and aminopeptidase N (CD 13 ), respectively. The longitudinal relaxivity (r 1 ) value of S8 was 8.297 mM -1 sec -1 at a magnetic field of 11.7 T, which is approximately double the r 1 value (4.25 mM -1 sec -1 ) of Magnevist, a commercially available contrast agent. MDA-MB-231 human breast cancer cells (which overexpress α v β 3 ) and human prostate cancer cells PC-3 (which overexpress CD 13 ) were used to investigate the tumor-targeting behavior of S8. The results from the present study indicate that the designed contrast agent, S8, targets both MDA-MB-231 and PC-3 cells.

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“…We and others have been using multimeric cyclic RGD peptides to develop the integrin α v β 3 -targeted radiotracers to image rapidly growing and metastatic tumors in several tumor-bearing animal models [27][28][29][30][31][32][33][34][35][36][37][38][39]. The RGD peptides serve as the targeting biomolecules to carry radionuclide (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…99m Tc, 111 In and 64 Cu) to the integrin α v β 3 overexpressed on both tumor cells and endothelial cells of tumor neovasculature. Recently, we reported the 111 In-and 64 Culabeled cyclic RGDfK tetramer as radiotracers for SPECT and PET imaging of integrin α v β 3 expression in tumors [33,37]. Results from in vitro assays showed that the tetramer had higher integrin α v β 3 binding affinity than the dimer.…”

Section: Introductionmentioning

confidence: 99%

“…Results from in vitro assays showed that the tetramer had higher integrin α v β 3 binding affinity than the dimer. As a result, 111 In(DOTA-tetramer) and 64 Cu (DOTA-tetramer) (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraactic acid) both have high tumor uptake with long tumor retention [33,37]. The tetramer, E{E[c (RGDfK)] 2 } 2 , is a much better targeting biomolecule than the dimer, E[c(RGDfK)] 2 , with respect to the tumor uptake and T/B ratios of their radiotracers [28].…”

Section: Introductionmentioning

confidence: 99%

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Coligand effects on the solution stability, biodistribution and metabolism of the 99mTc-labeled cyclic RGDfK tetramer

Liu

Kim

Hsieh

et al. 2008

Nuclear Medicine and Biology

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In this study, we present the evaluation of two new ternary ligand 99m Tc complexes [ 99m Tc(HYNICtetramer)(tricine)(L)] (L = ISONIC and PDA) as potential radiotracers for tumor imaging. The athymic nude mice bearing the MDA-MB-435 human breast cancer xenografts were used to evaluate their biodistribution and metabolic properties. The solution stability data showed that [ 99m Tc (HYNIC-tetramer)(tricine)(L)] (L = ISONIC and PDA) had a significant (14% and 35%, respectively) at 6 h in the absence of excess ISONIC or PDA coligand. Biodistribution data clearly showed that [ 99m Tc(HYNIC-tetramer)(tricine)(PDA)] has much lower uptake in most organs of interest than [ 99m Tc(HYNIC-tetramer)(tricine)(ISONIC)] during the 2 h study period. Results from metabolism studies revealed that ~50% of [ 99m Tc(HYNIC-tetramer)(tricine)(ISONIC)] remained intact in feces samples at 120 min p.i. Only 10% of [ 99m Tc(HYNIC-tetramer)(tricine)(PDA)] remained intact in feces samples. The extent of metabolism correlates well with the radiotracer solution stability. The results from this and our previous studies clearly demonstrated that coligands (TPPTS, ISONIC and PDA) have a significant impact on tumor uptake, excretion kinetics and metabolism of the 99m Tc-labeled cyclic RGDfK tetramer. Among the three radiotracers evaluated in this tumor-bearing animal model, [ 99m Tc(HYNIC-tetramer)(tricine)(TPPTS)] remains the best with respect to blood clearance, tumor uptake, target/background ratios.

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Improved targeting of the αvβ3 integrin by multimerisation of RGD peptides

Cited by 201 publications

References 18 publications

Cell-penetrating and cell-targeting peptides in drug delivery

Cell-penetrating and cell-targeting peptides in drug delivery

In vitro assessment of the dual-targeting behavior of a peptide-based magnetic resonance imaging contrast agent

Coligand effects on the solution stability, biodistribution and metabolism of the 99mTc-labeled cyclic RGDfK tetramer

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