Evaluation of a radiolabelled cyclic DTPA-RGD analogue for tumour imaging and radionuclide therapy

Hagen, P. Martin van; Breeman, W. A. P.; Bernard, H.F.; Schaar, Michael; Mooij, Cornelia; Srinivasan, Ananth; Schmidt, Michelle; Krenning, Eric P.; Jong, Marion de

doi:10.1002/1097-0215(20000820)90:4<186::aid-ijc2>3.0.co;2-p

Cited by 107 publications

(37 citation statements)

References 23 publications

(21 reference statements)

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“…Similar results with regard to other peptides have been reported. 18,22,23 The expression of a v b 3 integrin in microvessels in rat liver and lung as well as in osteoclast and osteoblast has been identified. [24][25][26][27] This fact suggests that there might be an expression of a v b 3 integrin in microvessels in normal tissues as well as in normal cells.…”

Section: Discussionmentioning

confidence: 99%

α_vβ₃ Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

Yoshimoto

Ogawa

Washiyama

et al. 2008

Intl Journal of Cancer

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The a v b 3 integrin plays a pivotal role in angiogenesis and tumor metastasis. Angiogenic blood vessels overexpress a v b 3 integrin, as in tumor neovascularization, and a v b 3 integrin expression in other microvascular beds and organs is limited. Therefore, a v b 3 integrin is a suitable receptor for tumor-targeting imaging and therapy. Recently, tetrameric and dimeric RGD peptides have been developed to enhance specificity to a v b 3 integrin. In comparison to the corresponding monomeric peptide, however, these peptides show high levels of accumulation in kidney and liver. The purpose of this study is to evaluate tumor-targeting properties and the therapeutic potential of 111 In-and 90 Y-labeled monomeric RGD peptides in BALB/c nude mice with SKOV-3 human ovarian carcinoma tumors. DOTA-c(RGDfK) was labeled with 111 In or 90 Y and purified by HPLC. A biodistribution study and scintigraphic images revealed the specific uptake to a v b 3 integrin and the rapid clearance from normal tissues. These peptides were renally excreted. At 10 min after injection of tracers, 111 In-DOTA-c(RGDfK) and 90 Y-DOTA-c(RGDfK) showed high uptake in tumors (7.3 6 0.6% ID/g and 4.6 6 0.8% ID/g, respectively) and gradually decreased over time (2.3 6 0.4% ID/g and 1.5 6 0.5% ID/g at 24 hr, respectively). High tumor-to-blood and -muscle ratios were obtained from these peptides. In radionuclide therapeutic study, multipledose administration of 90 Y-DOTA-c(RGDfK) (3 3 11.1 MBq) suppressed tumor growth in comparison to the control group and a single-dose administration ( The a v b 3 integrin recognizes the amino acid sequence of arginine-glycine-aspartic acid (RGD peptide). On the basis of the RGD peptide, many peptidomimetic compounds and peptides have been designed to antagonize the a v b 3 integrin. 4 These compounds and anti-a v b 3 integrin monoclonal antibodies have been reported to inhibit angiogenesis without affecting preexisting vessels. 2,5,6 Because of its restricted expression, the a v b 3 integrin is an attractive targeting molecule for tumor imaging and therapy, leading to decreased side effects compared to conventional chemotherapy.The expression of the a v b 3 integrin has been reported to be associated with metastatic potential in melanoma, breast cancer, and colon cancer. 7-9 The development of radiopharmaceuticals for targeting the a v b 3 integrin would be clinically beneficial, not only for screening and for treating patients with a v b 3 integrin-positive tumors but also for monitoring therapeutic efficacy.Many RGD peptides labeled with gamma-emitting and positron-emitting nuclides ( 18 F, 64 Cu, 99m Tc, 125 I, etc.) have been reported as angiogenesis-imaging agents. 10 A recent trend in the development of RGD peptides is the multimerization of RGD peptides to improve the high tumor accumulation and retention of RGD peptides. 11 However, this also leads to the enhancement of radioactive accumulation in nontargeted organs such as kidney and liver. 12 Compared with antibody or multimeric RGD peptides, monomeric RGD ...

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Section: Discussionmentioning

confidence: 99%

α_vβ₃ Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

Yoshimoto

Ogawa

Washiyama

et al. 2008

Intl Journal of Cancer

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“…Van Hagen et al studied the cyclic peptide c(RGDyK) conjugated with DTPA. 9 Uptake of the 111 In-labeled peptide in CA20948 pancreatic tumors in rats amounted to 0.2 %ID/g at 24 hour p.i., while at this timepoint, the peptide was almost completely cleared from the blood (0.003 %ID/g).…”

Section: Introductionmentioning

confidence: 99%

Improved Tumor Targeting of Radiolabeled RGD Peptides Using Rapid Dose Fractionation

Janssen

Frielink

Dijkgraaf

et al. 2004

Cancer Biotherapy and Radiopharmaceuticals

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“…Compounds containing the RGD peptide sequence are currently used as either antiangiogenic drugs (14)(15)(16)(17) or carriers for radioisotopes (8,12,13) to target a variety of integrins. The improved binding affinity of cyclic peptides to integrins has inspired numerous research efforts toward their use in biomedical research (28)(29)(30).…”

Section: Resultsmentioning

confidence: 95%

“…Based on structural and bioactivity considerations, cyclic RGD peptide ligands are preferentially used as delivery vehicles for molecular probes for imaging (8,(11)(12)(13) and treating (14-17) ABI-positive tumors and proliferating blood vessels. Until recently, most of the in vivo imaging studies were performed with radiopharmaceuticals because of the high sensitivity and clinical utility of nuclear imaging methods.…”

mentioning

confidence: 99%

Synergistic effects of light-emitting probes and peptides for targeting and monitoring integrin expression

Achilefu

Bloch²,

Markiewicz³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

119

113

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mouse ͉ optical imaging ͉ RGD peptides ͉ tumor ͉ near-infrared A ngiogenesis, the formation of new blood vessels, is the cardinal feature of virtually all malignant tumors (1). Because of this commonality, probing tumor-induced angiogenesis and associated proteins is a viable approach to detect and treat a wide range of cancers. Angiogenesis is stimulated by integrins, a large family of transmembrane proteins that mediate dynamic linkages between extracellular adhesion molecules and the intracellular actin skeleton. Integrins are composed of two different subunits, ␣ and ␤, which are noncovalently bound into ␣␤ complexes (2-4). Particularly, the expression of ␣ v ␤ 3 integrin (ABI) in tumor cells undergoing angiogenesis and on the epithelium of tumor-induced neovasculature alters the interaction of cells with the extracellular matrix, thereby increasing tumorigenicity and invasiveness of cancers (5-9).Numerous studies have shown that ABI and more than seven other heterodimeric integrins recognize proteins and low molecular weight ligands containing RGD (arginine-glycineaspartic acid) motifs in proteins and small peptides (10). Based on structural and bioactivity considerations, cyclic RGD peptide ligands are preferentially used as delivery vehicles for molecular probes for imaging (8,(11)(12)(13) and treating (14-17) ABI-positive tumors and proliferating blood vessels. Until recently, most of the in vivo imaging studies were performed with radiopharmaceuticals because of the high sensitivity and clinical utility of nuclear imaging methods. Particularly, the use of small monoatomic radioisotopes does not generally interfere with the biodistribution and bioactivity of ligands. Despite these advantages, nuclear imaging is currently only performed in specialized centers because of regulatory, production, and handling issues associated with radiopharmaceuticals. Optical imaging is an alternative but complementary method to interrogate molecular processes in vivo and in vitro.Optical imaging for biomedical applications typically relies on activating chromophore systems with low energy radiation between 400 -and 1,500-nm wavelengths and monitoring the propagation of light in deep tissues with a charge-coupled device camera or other point source detectors (18). Molecular optical imaging of diseases with molecular probes is attractive because of the flexibility of altering the detectable spectral properties of the probes, especially in the fluorescence detection mode. The probes can be designed to target cellular and molecular processes at functional physiological concentrations. For deep-tissue imaging, molecular probes that are photoactive in the near-infrared (NIR) instead of visible wavelengths are preferred to minimize background tissue autof luorescence and light attenuation caused by absorption by intrinsic chromophores (19). In contrast to radioisotopes, the NIR antennas are usually large heteroatomic molecules that could impact the biodistribution and activity of conjugated bioactive ligands. However, previous s...

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Evaluation of a radiolabelled cyclic DTPA-RGD analogue for tumour imaging and radionuclide therapy

Cited by 107 publications

References 23 publications

α_vβ₃ Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

α_vβ₃ Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

Improved Tumor Targeting of Radiolabeled RGD Peptides Using Rapid Dose Fractionation

Synergistic effects of light-emitting probes and peptides for targeting and monitoring integrin expression

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Evaluation of a radiolabelled cyclic DTPA-RGD analogue for tumour imaging and radionuclide therapy

Cited by 107 publications

References 23 publications

αvβ3 Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

αvβ3 Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

Improved Tumor Targeting of Radiolabeled RGD Peptides Using Rapid Dose Fractionation

Synergistic effects of light-emitting probes and peptides for targeting and monitoring integrin expression

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Product

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α_vβ₃ Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide

α_vβ₃ Integrin‐targeting radionuclide therapy and imaging with monomeric RGD peptide