Theranostics2016 4th Theranostics World Congress 2016 Innovative Theranostics (17 abstracts)
Noninvasive imaging of multiple Myeloma with 68Ga-DOTA-PEG4-LLP2A via targeting VLA-4
Nilantha Bandara 1 , Deep Hathi 2 , Walter J Akers 2 , Richard Laforest 2 , Kooresh I Shoghi 2 , Buck E Rogers 1, & Monica Shokeen 2
1Radiation Oncology, Division of Cancer Biology, Washington University School of Medicine, St Louis, MO, USA; 2Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, USA.
Multiple myeloma (MM) is a B-cell tumor of monoclonal plasma cells in the bone marrow and is the second most common age-related hematologic malignancy reported in the United States. Very late antigen-4 (VLA-4, α4β1 integrin, CD49d/CD29) is overexpressed on MM. LLP2A is a highly specific peptidomimetic ligand that targets activated VLA-4 with high affinity. In this study, we evaluated 68Ga radiolabeled-DOTA-PEG4-LLP2A tracer as a PET agent for of MM.
The stability of the radiolabeled complex was evaluated with in vitro human serum and found to be >98% intact up to 3 h. Imaging studies were conducted in C57BL6/KaLwRij mice bearing 5TGM1-GFP tumors with i.v., intratibial and xenograft models. Ex vivo autoradiography and histology analysis were conducted on tumor sections to evaluate intra-tumoral distribution. Logan analysis of 68Ga-LLP2A uptake in intra-tibia region was performed using 0-60 minute dynamic imaging data. 68Ga-LLP2A exhibited clear saturable binding to target receptors with distribution volume (DV) indicated on the plot for tumor (T) and muscle (M) (Figure 1). The calculated binding potential (BP=Bmax/Kd) based on this data is BP=6.04.
Human organ radiation dose estimates were calculated by extrapolating biodistribution data from normal C57BL6 mice. The bladder was the dose limiting organ for both male and female mice (1.08 and 1.46 rad/mCi respectively). Toxicity studies will be completed in near future. Overall, 68Ga-DOTA-PEG4-LLP2A displayed good tumor targeting and favorable dosimetry. Thus, we plan to carry this agent forward in future human studies as a noninvasive imaging agent for overexpressed VLA-4 in MM.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more