Imaging of metastatic melanoma utilising a technetium-99m labelled RGD-containing synthetic peptide

Sivolapenko, Gregory; Skarlos, D.; Pectasides, Demitris; Stathopoulou, Evaggelia; Milonakis, Alexandros; Sirmalis, G; Stuttle, A. W. J.; Courtenay-Luck, Nigel; Κωνσταντινίδης, Κωνσταντίνος; Epenetos, Agamemnon A.

doi:10.1007/s002590050312

Cited by 94 publications

(60 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The results reported here describe how these tumors models have enabled us to verify the potential of 111 In-RGD 2 as a specific antiangiogenic marker in HNSCC, a feature that, despite much clinical and preclinical research into radiolabeled RGD peptides as a tracer for integrin a v b 3 (11,18,20,25,26), was still uncertain. SPECT/CT imaging showed clear uptake of the tracer in areas corresponding with vascularized areas of the tumor.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Imaging Integrin α_vβ₃ on Blood Vessels with ¹¹¹In-RGD₂ in Head and Neck Tumor Xenografts

et al. 2014

View full text Add to dashboard Cite

Arginine-glycine-aspartic acid (RGD)-based imaging tracers allow specific imaging of integrin a v b 3 , a protein overexpressed during angiogenesis, leading to the possibility that it might serve as a tool to stratify patients for antiangiogenic treatment. However, these tracers have generally been characterized in xenograft models in which integrin a v b 3 was constitutively expressed by the tumor cells themselves. In the studies presented here, the use of 111 In-RGD 2 as a tracer to image only integrin a v b 3 expression on blood vessels in the tumor was determined using tumor xenografts in which tumor cells were integrin a v b 3 -negative. Methods: DOTA-E-[c(RGDfK)] 2 was radiolabeled with 111 In ( 111 In-RGD 2 ), and biodistribution studies were performed in squamous cell carcinoma of the head and neck (HNSCC) xenograft mouse models to determine the optimal peptide dose to image angiogenesis. Next, biodistribution and imaging studies were performed at the optimal peptide dose in 3 HNSCC mouse models, FaDu, SCCNij3, and SCCNij202. Immunohistochemical analysis of tumor vascular and cell surface expression of integrin a v b 3 and correlation analysis of vascular integrin a v b 3 and autoradiography were completed. Results: All 3 HNSCC xenografts expressed integrin a v b 3 on the vessels only. The optimal peptide dose of 111 In-RGD 2 was 1 mg or less for specific integrin a v b 3 -mediated uptake of the tracer. SPECT/CT imaging showed clear uptake of the tracer in the periphery of the tumors, corresponding with wellvascularized areas of the tumor. Within the tumor, 111 In-RGD 2 autoradiography coincided with vascular integrin a v b 3 expression, as determined immunohistochemically. Integrin a v b 3 -mediated uptake was also detected in nontumor tissues, which, through immunohistochemical analysis, proved positive for integrin a v b 3 . Conclusion: 111 In-RGD 2 allows the visualization of integrin a v b 3 in xenograft models in which integrin a v b 3 is expressed only on the neovasculature, such as in the HNSCC tumors. Thus, 111 In-RGD 2 allows specific visualization of angiogenesis in tumor models lacking constitutive tumoral integrin a v b 3 expression but may be less useful for this purpose in many tumors in which tumor cells express integrin a v b 3 .

show abstract

Section: Discussionmentioning

confidence: 99%

“…In micro-SPECT imaging studies, mice with FaDu, SCCNij3, or SCCNij202 tumor xenografts were injected intravenously with 1 mg of 111 In-RGD 2 (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). A 50-fold cold excess of RGD 2 was coinjected to investigate receptor-mediated localization of the radiolabeled peptide.…”

Section: Micro-spect/ctmentioning

confidence: 99%

Imaging Integrin α_vβ₃ on Blood Vessels with ¹¹¹In-RGD₂ in Head and Neck Tumor Xenografts

et al. 2014

View full text Add to dashboard Cite

show abstract

“…99m Tc-αP2 99m Tc-αP2 is a peptide comprised of ten amino acids that contains two copies of the RGD motif for integrin-specific binding, and coupling to 99m Tc was accomplished over cysteine residues introduced into the peptide. 99m Tc-αP2 for imaging of integrin expression had been reported in 1988, even before integrin-specific PET tracers became available [60]. A clinical study in patients with malignant melanoma revealed a good detection rate of metastases in the neck, axilla, abdomen and soft tissue; however, sensitivity was reported to be low in the thorax due to high blood pool activity in the heart.…”

Section: Multimeric Compoundsmentioning

confidence: 96%

Radiolabelled RGD peptides for imaging and therapy

Gaertner

Kessler

Wester³

et al. 2012

Eur J Nucl Med Mol Imaging

209

191

View full text Add to dashboard Cite

Imaging of angiogenesis has become increasingly important with the rising use of targeted antiangiogenic therapies like bevacizumab (Avastin). Non-invasive assessment of angiogenic activity is in this respect interesting, e.g. for response assessment of such targeted antiangiogenic therapies. One promising approach of angiogenesis imaging is imaging of specific molecular markers of the angiogenic cascade like the integrin α(v)β(3). For molecular imaging of integrin expression, the use of radiolabelled peptides is still the only approach that has been successfully translated into the clinic. In this review we will summarize the current data on imaging of α(v)β(3) expression using radiolabelled RGD peptides with a focus on tracers already in clinical use. A perspective will be presented on the future clinical use of radiolabelled RGD peptides including an outlook on potential applications for radionuclide therapy.

show abstract

“…52 Since platelets are a major, biologically active constituent of a thrombus, there may be an advantage in using platelettargeted agents. 53 In the fast growing thrombus, platelets are activated. The activated platelets express the cellsurface integrin glycoprotein IIb/IIIa (GPIIb/IIIa) receptor which recognizes peptides containing the Arg-Gly-Asp (RGD) sequence, whereas non-activated circulating platelets express virtually none of the receptor in its active conformation.…”

Section: T H R O M B U S I M a G I N G P E P T I D E R A D I O P H mentioning

confidence: 99%

Peptide‐based radiopharmaceuticals: Future tools for diagnostic imaging of cancers and other diseases

Okarvi

2004

Medicinal Research Reviews

205

116

View full text Add to dashboard Cite

Small synthetic receptor-binding peptides are the agents of choice for diagnostic imaging and radiotherapy of cancers due to their favorable pharmacokinetics. Molecular modification techniques permit the synthesis of a variety of bioactive peptides with chelating groups, without compromising biological properties. Various techniques have been developed that allow efficient and site-specific labeling of peptides with clinically useful radionuclides such as (99m)Tc, (123)I, (111)In, and (18)F. Among them, (99m)Tc is the radionuclide of choice because of its excellent chemical and imaging characteristics. Recently, many (99m)Tc-labeled peptides have proven to be useful imaging agents. Beside (99m)Tc-labeled peptides, several peptides radiolabeled with (111)In and (123)I have been prepared and characterized. In addition, (18)F-labeled peptides hold clinical potential due to their ability to quantitatively detect and characterize a variety of human diseases using positron-emission tomography. The availability of this wide range of peptides labeled with different radionuclides offers multiple diagnostic and therapeutic applications. Various receptors are over-expressed in particular tumor types and peptides binding to these receptors can be used to visualize tumor lesions scintigraphically. Thus, radiolabeled peptides have potential use as carriers for the delivery of radionuclides to tumors, infarcts, and infected tissues for diagnostic imaging and radiotherapy. Many radiolabeled peptides are currently under investigation to determine their potential as imaging agents. These peptides are designed mainly for thrombus, tumor, and infection/inflammation imaging. This article presents recent developments in small synthetic peptides for imaging of thrombosis, tumors, and infection/inflammation.

show abstract

Imaging of metastatic melanoma utilising a technetium-99m labelled RGD-containing synthetic peptide

Cited by 94 publications

References 18 publications

Imaging Integrin α_vβ₃ on Blood Vessels with ¹¹¹In-RGD₂ in Head and Neck Tumor Xenografts

Imaging Integrin α_vβ₃ on Blood Vessels with ¹¹¹In-RGD₂ in Head and Neck Tumor Xenografts

Radiolabelled RGD peptides for imaging and therapy

Peptide‐based radiopharmaceuticals: Future tools for diagnostic imaging of cancers and other diseases

Contact Info

Product

Resources

About

Imaging of metastatic melanoma utilising a technetium-99m labelled RGD-containing synthetic peptide

Cited by 94 publications

References 18 publications

Imaging Integrin αvβ3 on Blood Vessels with 111In-RGD2 in Head and Neck Tumor Xenografts

Imaging Integrin αvβ3 on Blood Vessels with 111In-RGD2 in Head and Neck Tumor Xenografts

Radiolabelled RGD peptides for imaging and therapy

Peptide‐based radiopharmaceuticals: Future tools for diagnostic imaging of cancers and other diseases

Contact Info

Product

Resources

About

Imaging Integrin α_vβ₃ on Blood Vessels with ¹¹¹In-RGD₂ in Head and Neck Tumor Xenografts

Imaging Integrin α_vβ₃ on Blood Vessels with ¹¹¹In-RGD₂ in Head and Neck Tumor Xenografts