Imaging integrin alpha‐v‐beta‐3 expression in tumors with an <sup>18</sup>F‐labeled dimeric RGD peptide

Dijkgraaf, Ingrid; Terry, Samantha Y.A.; McBride, William J.; Goldenberg, David M.; Laverman, Peter; Franssen, Gerben M.; Oyen, Wim J.G.; Boerman, Otto C.

doi:10.1002/cmmi.1523

Cited by 37 publications

(33 citation statements)

References 38 publications

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“…A similar tumor uptake of 6 %ID/g was seen in the renal cell carcinoma SK-RC-52 model, in which, as in the ovarian carcinoma tumors, integrin a v b 3 is also expressed constitutively on the tumor cells (15,19). Uptake of other radiolabeled dimeric RGD tracers also averaged around 5-10 %ID/g in the SK-RC-52, OVCAR-3, and glioma tumor models (17,(30)(31)(32)(33). The average uptake of 111 In-RGD 2 in the HNSCC tumors approximates 1.3 %ID/g, suggesting that only vascular integrin a v b 3 expression has any influence on the tumor uptake of 111 In-RGD 2 and that therefore total tumor uptake is lower than in tumor models in which integrin a v b 3 is expressed constitutively.…”

Section: Discussionsupporting

confidence: 55%

“…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%

“…Radiolabeled peptides proved a good tracer for imaging tumors expressing integrin a v b 3 by either PET or SPECT and for imaging non-tumor-associated angiogenesis (16). The efficacy of using these peptides was determined with ovarian, renal cell carcinoma, and glioblastoma preclinical models (12,15,(17)(18)(19); however, these models are not ideal to determine whether RGD-based tracers allow the imaging of angiogenesis because tumoral expression of integrin a v b 3 was not excluded. In general, therefore, because of the constitutive integrin a v b 3 on tumor cells, these models do not allow the effects of constitutive integrin a v b 3 expression to be isolated from vascular integrin expression.…”

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confidence: 99%

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

et al. 2014

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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 .

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Section: Discussionsupporting

confidence: 55%

Section: Micro-spect/ctmentioning

confidence: 99%

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confidence: 99%

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

et al. 2014

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“…In previous studies, the authors did not see accumulation of any of the tracers in the joints of nonarthritic mice (8,12,13,18). The 3 tracers are different with regard to their targets, mechanism, and pharmacokinetics; they all measure something different, so a straight comparison was not performed here.…”

Section: Discussionmentioning

confidence: 92%

“…The affinity of all 3 tracers and the immunoreactive fraction of anti-F4/80-A3-1 (75%) have been determined previously (8,13,18). The immunoreactive fraction for 111 In-28H1 was 91.4% (Supplemental Fig.…”

Section: Antibody Conjugation and Rgd Peptidementioning

confidence: 90%

Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin α_vβ₃

et al. 2015

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Rheumatoid arthritis is an autoimmune disease resulting in chronic synovial inflammation. Molecular imaging could be used to monitor therapy response, thus enabling tailored therapy regimens and enhancing therapeutic outcome. Here, we hypothesized that response to etanercept could be monitored by radionuclide imaging in arthritic mice. We tested 3 different targets, namely fibroblast activation protein (FAP), macrophages, and integrin α v β 3 . Methods: Male DBA/1J mice with collagen-induced arthritis were treated with etanercept. SPECT/ CT scans were acquired at 1, 24, and 48 h after injection of 111 In-RGD 2 (integrin α v β 3 ), 111 In-anti-F4/80-A3-1 (antimurine macrophage antibody), or 111 In-28H1 (anti-FAP antibody), respectively, with nonspecific controls included. Mice were dissected after the last scan, and scans were analyzed quantitatively and were correlated with macroscopic scoring. Results: Experimental arthritis was imaged with 111 In-28H1 (anti-FAP), 111 In-anti-F4/80-A3-1, and 111 In-RGD 2 . Tracer uptake in joints correlated with arthritis score. Treatment decreased joint uptake of tracers from 23 ± 15, 8 ± 4, and 2 ± 1 percentage injected dose per gram (%ID/g) to 11 ± 11 (P , 0.001), 4 ± 4 (P , 0.001), and 1 ± 0.2 %ID/g (P , 0.01) for 111 In-28H1, 111 In-anti-F4/80-A3-1, and 111 In-RGD 2 , respectively. Arthritis-to-blood ratios (in mice with arthritis score 2 per joint) were higher for 111 In-28H1 (5.5 ± 1; excluding values . 25), 111 In-anti-F4/80-A3-1 (10.4 ± 4), and 111 In-RGD 2 (7.2 ± 1) than for control 111 In-DP47GS (0.7 ± 0.5; P 5 0.002), 111 In-rat IgG2b (0.5 ± 0.2; P 5 0.002), or coinjection of excess RGD 2 (3.5), indicating specific uptake of all tracers in arthritic joints. Conclusion: 111 In-28H1, 111 In-anti-F4/80-A3-1, and 111 In-RGD 2 can be used to specifically monitor the response to therapy in experimental arthritis at the molecular level. Further studies, however, still need to be performed.

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¹⁸F‐Labeling Chemistry in Aqueous Media

Zhang

Feng

Mou

et al. 2023

Chemistry A European J

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Imaging integrin alpha‐v‐beta‐3 expression in tumors with an ¹⁸F‐labeled dimeric RGD peptide

Cited by 37 publications

References 38 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

Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin α_vβ₃

¹⁸F‐Labeling Chemistry in Aqueous Media

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Imaging integrin alpha‐v‐beta‐3 expression in tumors with an 18F‐labeled dimeric RGD peptide

Cited by 37 publications

References 38 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

Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin αvβ3

18F‐Labeling Chemistry in Aqueous Media

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Imaging integrin alpha‐v‐beta‐3 expression in tumors with an ¹⁸F‐labeled dimeric RGD peptide

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

Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin α_vβ₃

¹⁸F‐Labeling Chemistry in Aqueous Media