TITLE

Very Late Antigen-4 (α4β1 Integrin) Targeted PET Imaging of Multiple Myeloma

AUTHOR(S)
Soodgupta, Deepti; Hurchla, Michelle A.; Jiang, Majiong; Zheleznyak, Alexander; Weilbaecher, Katherine N.; Anderson, Carolyn J.; Tomasson, Michael H.; Shokeen, Monica
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Biomedical imaging techniques such as skeletal survey and 18F-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 α4β1 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, 64Cu-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 64Cu-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 64Cu-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, 64Cu-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 64Cu-CB-TE1A1P-LLP2A is a novel approach to imaging MM tumors.
ACCESSION #
87624044

 

Related Articles

  • Extramedullary disease in plasma cell myeloma: the iceberg phenomenon. Wirk, B; Wingard, J R; Moreb, J S // Bone Marrow Transplantation;Jan2013, Vol. 48 Issue 1, p10 

    Extramedullary (EM) plasmacytomas (EMPs) that are not progression of intramedullary (IM) plasma cell myeloma (PCM) are usually indolent. In contrast, EM spread of IM PCM is associated with a poor prognosis. The recently introduced Durie-Salmon PLUS staging system includes EM disease in the poor...

  • Role of 18F-FDG PET/CT in the assessment of bone involvement in newly diagnosed multiple myeloma: preliminary results. Nanni, Cristina; Zamagni, Elena; Farsad, Mohsen; Castellucci, Paolo; Tosi, Patrizia; Cangini, Delia; Salizzoni, Eugenio; Canini, Romeo; Cavo, Michele; Fanti, Stefano // European Journal of Nuclear Medicine & Molecular Imaging;May2006, Vol. 33 Issue 5, p525 

    Purpose: Multiple myeloma (MM) is a malignant B cell and plasma cell disorder which involves the skeleton in more than 80% of patients at diagnosis. The aim of this study was to compare whole-body X-ray (WBXR), MRI and 18F-FDG PET/CT in patients with MM. Methods: The study population comprised...

  • The Role of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in Evaluating the Response to Treatment in Patients with Multiple Myeloma. Caldarella, Carmelo; Treglia, Giorgio; Isgrò, Maria Antonietta; Treglia, Ivan; Giordano, Alessandro // International Journal of Molecular Imaging;2012, p1 

    Background and Aim. Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is well recognized as a powerful diagnostic tool in the initial staging of patients with multiple myeloma (MM). The aim of this paper is to perform a systematic review about the usefulness of FDG-PET or...

  • Multiple Myeloma of the Cricoid Cartilage. Yoskovitch, Adi; Al-Abdulhadi, Khaled; Wright, Erin D.; Watters, Andrew K.; Chagnon, Francoise // Journal of Otolaryngology;May/Jun1998, Vol. 27 Issue 3, p168 

    Presents a case of cricoid involvement in a patient with known multiple myeloma (MM), the most common form of the plasma cell dyscrasias. Symptoms of MM in the head and neck region; Categories of the disease when looking at plasma cell tumors of the head and neck; Treatment of MM; Alternative...

  • Laminin-1-induced migration of multiple myeloma cells involves the high-affinity 67 kD laminin receptor. Vande Broek, I; Vanderkerken, K; De Greef, C; Asosingh, K; Straetmans, N; Van Camp, B; Van Riet, I // British Journal of Cancer;11/1/2001, Vol. 85 Issue 9, p1387 

    The 67 kD laminin receptor (67LR) binds laminin-1 (LN), major component of the basement membrane, with high affinity. In this study, we demonstrated that human multiple myeloma cell lines (HMCL) and murine 5T2MM cells express 67LR. CD38[SUPbright+] plasma cells in fresh multiple myeloma (MM)...

  • Role of Tc-99m sestamibi myocardial perfusion imaging in identifying multiple myeloma. Kalaga, Ravishankar; Kudagi, Vinod; Heller, Gary // Journal of Nuclear Cardiology;Sep2009, Vol. 16 Issue 5, p835 

    The article presents a case study of an 85-year-old Ukrainian male who is experiencing three-day-chest pain. It mentions that the Tc-99m sestamibi myocardial perfusion imaging was conducted to the patient using rest/stress protocol. It states that the patients undergo positron emission...

  • Initial results in the assessment of multiple myeloma using[sup 18] F-FDG PET. Schirrmeister, H.; Bommer, M.; Buck, K.; Müller, S.; Messer, P.; Bunjes, D.; Döhner, H.; Bergmann, L.; Reske, N. // European Journal of Nuclear Medicine & Molecular Imaging;2002, Vol. 29 Issue 3, p361 

    This prospective study was undertaken to investigate the appearance of multiple myeloma on fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET). Furthermore, the accuracy of FDG-PET in detecting myeloma lesions and its influence on patient management were evaluated. Forty-three...

  • VELCADE (VEL-kade) (INJECTION).  // Drug Topics;7/07/2003, Vol. 147 Issue 13, p28 

    Provides information on the drug Velcade for the treatment of multiple myeloma or blood plasma cell cancer. Generic name; How to use and store the medicine; Storage and disposal; Drugs and foods to avoid.

  • Serum bone sialoprotein as a marker of tumour burden and neoplastic bone involvement and as a prognostic factor in multiple myeloma. Woitge, H W; Pecherstorfer, M; Horn, E; Keck, A-V; Diel, I J; Bayer, P; Ludwig, H; Ziegler, R; Seibel, M J // British Journal of Cancer;2/1/2001, Vol. 84 Issue 3, p344 

    To test the potential of immunoreactive BSP, a non-collagenous bone matrix component, as a clinical guide in patients with plasma cell dyscrasias, serum BSP concentrations were measured in 62 patients with newly diagnosed multiple myeloma (MM) followed over a period of 4 years, in 46 patients...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics