Very late antigen-4 (α(4)β(1) Integrin) targeted PET imaging of multiple myeloma.
Biomedical imaging techniques such as skeletal survey and (18)F-fluorodeoxyglucose (FDG)/Positron Emission Tomography (PET) are frequently used to diagnose and stage multiple myeloma (MM) patients. However, skeletal survey has limited sensitivity as it can detect osteolytic lesions only after 30-50%...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3568146?pdf=render |
| _version_ | 1818133608707129344 |
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| author | Deepti Soodgupta Michelle A Hurchla Majiong Jiang Alexander Zheleznyak Katherine N Weilbaecher Carolyn J Anderson Michael H Tomasson Monica Shokeen |
| author_facet | Deepti Soodgupta Michelle A Hurchla Majiong Jiang Alexander Zheleznyak Katherine N Weilbaecher Carolyn J Anderson Michael H Tomasson Monica Shokeen |
| author_sort | Deepti Soodgupta |
| collection | DOAJ |
| description | Biomedical imaging techniques such as skeletal survey and (18)F-fluorodeoxyglucose (FDG)/Positron Emission Tomography (PET) are frequently used to diagnose and stage multiple myeloma (MM) patients. However, skeletal survey has limited sensitivity as it can detect osteolytic lesions only after 30-50% cortical bone destruction, and FDG is a marker of cell metabolism that has limited sensitivity for intramedullary lesions in MM. Targeted, and non-invasive novel probes are needed to sensitively and selectively image the unique molecular signatures and cellular processes associated with MM. Very late antigen-4 (VLA-4; also called α(4)β(1) integrin) is over-expressed on MM cells, and is one of the key mediators of myeloma cell adhesion to the bone marrow (BM) that promotes MM cell trafficking and drug resistance. Here we describe a proof-of-principle, novel molecular imaging strategy for MM tumors using a VLA-4 targeted PET radiopharmaceutical, (64)Cu-CB-TE1A1P-LLP2A. Cell uptake studies in a VLA-4-positive murine MM cell line, 5TGM1, demonstrated receptor specific uptake (P<0.0001, block vs. non-block). Tissue biodistribution at 2 h of (64)Cu-CB-TE1A1P-LLP2A in 5TGM1 tumor bearing syngeneic KaLwRij mice demonstrated high radiotracer uptake in the tumor (12±4.5%ID/g), and in the VLA-4 rich organs, spleen (8.8±1.0%ID/g) and marrow (11.6±2.0%ID/g). Small animal PET/CT imaging with (64)Cu-CB-TE1A1P-LLP2A demonstrated high uptake in the 5TGM1 tumors (SUV 6.6±1.1). There was a 3-fold reduction in the in vivo tumor uptake in the presence of blocking agent (2.3±0.4). Additionally, (64)Cu-CB-TE1A1P-LLP2A demonstrated high binding to the human MM cell line RPMI-8226 that was significantly reduced in the presence of the cold targeting agent. These results provide pre-clinical evidence that VLA-4-targeted imaging using (64)Cu-CB-TE1A1P-LLP2A is a novel approach to imaging MM tumors. |
| first_indexed | 2024-12-11T08:55:26Z |
| format | Article |
| id | doaj.art-9af816aa1d8043debbb5a5bddc96b4de |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T08:55:26Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-9af816aa1d8043debbb5a5bddc96b4de2022-12-22T01:13:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5584110.1371/journal.pone.0055841Very late antigen-4 (α(4)β(1) Integrin) targeted PET imaging of multiple myeloma.Deepti SoodguptaMichelle A HurchlaMajiong JiangAlexander ZheleznyakKatherine N WeilbaecherCarolyn J AndersonMichael H TomassonMonica ShokeenBiomedical imaging techniques such as skeletal survey and (18)F-fluorodeoxyglucose (FDG)/Positron Emission Tomography (PET) are frequently used to diagnose and stage multiple myeloma (MM) patients. However, skeletal survey has limited sensitivity as it can detect osteolytic lesions only after 30-50% cortical bone destruction, and FDG is a marker of cell metabolism that has limited sensitivity for intramedullary lesions in MM. Targeted, and non-invasive novel probes are needed to sensitively and selectively image the unique molecular signatures and cellular processes associated with MM. Very late antigen-4 (VLA-4; also called α(4)β(1) integrin) is over-expressed on MM cells, and is one of the key mediators of myeloma cell adhesion to the bone marrow (BM) that promotes MM cell trafficking and drug resistance. Here we describe a proof-of-principle, novel molecular imaging strategy for MM tumors using a VLA-4 targeted PET radiopharmaceutical, (64)Cu-CB-TE1A1P-LLP2A. Cell uptake studies in a VLA-4-positive murine MM cell line, 5TGM1, demonstrated receptor specific uptake (P<0.0001, block vs. non-block). Tissue biodistribution at 2 h of (64)Cu-CB-TE1A1P-LLP2A in 5TGM1 tumor bearing syngeneic KaLwRij mice demonstrated high radiotracer uptake in the tumor (12±4.5%ID/g), and in the VLA-4 rich organs, spleen (8.8±1.0%ID/g) and marrow (11.6±2.0%ID/g). Small animal PET/CT imaging with (64)Cu-CB-TE1A1P-LLP2A demonstrated high uptake in the 5TGM1 tumors (SUV 6.6±1.1). There was a 3-fold reduction in the in vivo tumor uptake in the presence of blocking agent (2.3±0.4). Additionally, (64)Cu-CB-TE1A1P-LLP2A demonstrated high binding to the human MM cell line RPMI-8226 that was significantly reduced in the presence of the cold targeting agent. These results provide pre-clinical evidence that VLA-4-targeted imaging using (64)Cu-CB-TE1A1P-LLP2A is a novel approach to imaging MM tumors.http://europepmc.org/articles/PMC3568146?pdf=render |
| spellingShingle | Deepti Soodgupta Michelle A Hurchla Majiong Jiang Alexander Zheleznyak Katherine N Weilbaecher Carolyn J Anderson Michael H Tomasson Monica Shokeen Very late antigen-4 (α(4)β(1) Integrin) targeted PET imaging of multiple myeloma. PLoS ONE |
| title | Very late antigen-4 (α(4)β(1) Integrin) targeted PET imaging of multiple myeloma. |
| title_full | Very late antigen-4 (α(4)β(1) Integrin) targeted PET imaging of multiple myeloma. |
| title_fullStr | Very late antigen-4 (α(4)β(1) Integrin) targeted PET imaging of multiple myeloma. |
| title_full_unstemmed | Very late antigen-4 (α(4)β(1) Integrin) targeted PET imaging of multiple myeloma. |
| title_short | Very late antigen-4 (α(4)β(1) Integrin) targeted PET imaging of multiple myeloma. |
| title_sort | very late antigen 4 α 4 β 1 integrin targeted pet imaging of multiple myeloma |
| url | http://europepmc.org/articles/PMC3568146?pdf=render |
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