Integrin αvβ3 as a PET Imaging Biomarker for Osteoclast Number in Mouse Models of Negative and Positive Osteoclast Regulation

Zheleznyak, Alexander; Wadas, Thaddeus J.; Sherman, Christopher D.; Wilson, Jessica; Kostenuik, Paul J.; Weilbaecher, Katherine N.; Anderson, Carolyn J.

doi:10.1007/s11307-011-0512-4

Cited by 30 publications

(23 citation statements)

References 31 publications

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“…59 Recently, novel radiopharmaceuticals, such as very late antigen-4- and αβ3 integrin-targeted radiotracers, have been developed to image intramedullary or osteoclastic bone metastases more selectively and sensitively. 128,181 SPECT is more widely available and less expensive than PET, and the radiotracers tend to have a longer half-life (up to 6 hours) than PET tracers (approximately 75 seconds), making the use of PET sometimes limited. 59 …”

Section: Micro–positron Emission Tomography and Micro–single-photon Ementioning

confidence: 99%

Animal Models of Bone Metastasis

et al. 2015

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Bone is one of the most common sites of cancer metastasis in humans and is a significant source of morbidity and mortality. Bone metastases are considered incurable and result in pain, pathologic fracture, and decreased quality of life. Animal models of skeletal metastases are essential to improve the understanding of the molecular pathways of cancer metastasis and growth in bone and to develop new therapies to inhibit and prevent bone metastases. The ideal animal model should be clinically relevant, reproducible, and representative of human disease. Currently, an ideal model does not exist; however, understanding the strengths and weaknesses of the available models will lead to proper study design and successful cancer research. This review provides an overview of the current in vivo animal models used in the study of skeletal metastases or local tumor invasion into bone and focuses on mammary and prostate cancer, lymphoma, multiple myeloma, head and neck squamous cell carcinoma, and miscellaneous tumors that metastasize to bone.

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Section: Micro–positron Emission Tomography and Micro–single-photon Ementioning

confidence: 99%

Animal Models of Bone Metastasis

et al. 2015

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“…In dose-finding studies, arthritic male DBA/1J mice were injected intravenously with either 10 In-rat IgG2b), and 1 h ( 111 In-RGD 2 ) after tracer injection, mice were euthanized by CO 2 /O 2 asphyxiation for ex vivo biodistribution studies (3 mice/group). Mice were then scanned with the U-SPECT-II/CT scanner (MILabs) while in the prone position.…”

Section: Biodistribution Studiesmentioning

confidence: 99%

“…One of the most prominent cell populations is activated fibroblastlike synoviocytes (6), which express fibroblast activation protein (FAP) (7) and could be imaged by micro-SPECT using radiolabeled antibodies against FAP, as shown by us recently (8). Other cell types include osteoclasts (9), which express integrin a v b 3 (10). Integrin a v b 3 is a much-used target for imaging tumor cells and angiogenesis in oncology using radiolabeled RGD peptides.…”

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confidence: 99%

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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“…To date, only 2 research groups investigated this matter: two studies imaging osteoclast function in mice and one imaging synovial angiogenesis in patients with RA [28][29][30].…”

Section: Introductionmentioning

confidence: 99%