RT Journal Article
SR Electronic
T1 Molecular Imaging of Multiple Myeloma Targeting CD46 Using ImmunoPET
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 62
OP 62
VO 62
IS supplement 1
A1 Sinan Wang
A1 Yang Su
A1 Bonell Patino Escobar
A1 Veronica Steri
A1 Byron Hann
A1 Ryan Tang
A1 Youngho Seo
A1 Bin Liu
A1 Arun Wiita
A1 Robert Flavell
YR 2021
UL http://jnm.snmjournals.org/content/62/supplement_1/62.abstract
AB 62Introduction: The extensive heterogeneity in multiple myeloma (MM) emphasizes the need for accurate prognostic tools. 18F-FDG PET/CT imaging has been used for MM detection but false-negative 18F-FDG PET/CT in MM may be seen in some cases [1]. Therefore, there is an unmet clinical need for improved imaging biomarkers for the detection of MM. CD46 has been identified as a novel and underexplored therapeutic target in multiple myeloma. We have developed an antibody drug conjugate against CD46, which is now in phase 1 clinical trials [2]. In principle, a CD46-directed molecular imaging agent could be used as a companion biomarker for this ADC and other CD46-targeted therapies. Recently, we have developed an anti-CD46 positron emission tomography radiopharmaceutical, [89Zr]DFO-YS5, and demonstrated its sensitivity for the detection of prostate cancer [3]. In the present study, we evaluated [89Zr]DFO-YS5 for immunoPET imaging in murine MM models. Methods: [89Zr]DFO-YS5 was prepared based on our previous method [3], and a control, nonspecific [89Zr]DFO-IgG was prepared using similar methods. NSG mice bearing subcutaneous MM1.S-luc (luciferase expressing) xenograft tumor were prepared. Additionally, an orthometastatic model of myeloma was prepared by administration of the MM1.S-luc cell via tail vein in NSG mice. ImmunoPET imaging was performed at 6 days post injection for the subcutaneous model, and 4 days post injection in the orthometastatic model on a Siemens Inveon micro PET/CT, at which time the mice were sacrificed and biodistribution analysis was performed. For the orthometastatic model, uptake in the organs was compared against bioluminescence imaging after dissection. Results: [89Zr]DFO-YS5 binds specifically to the CD46 positive human MM1s subcutaneous xenografts. In biodistribution studies using the subcutaneous xenograft model, the tumor uptake of [89Zr]DFO-YS5 was 17.4 ± 3.6 % ID/g at 6 days post injection, significantly higher than the uptake of the blocked group (5.3 ± 1.4 % ID/g) and the nonspecific [89Zr]DFO-IgG group (3.7 ± 0.3 % ID/g) (Figure A-D). In the orthometastastic model, [89Zr]DFO-YS5 also demonstrated specific uptake in the bone marrow (16.7 ± 6.6% ID/g at 4 days post injection), higher than the uptake of the blocked group (4.2 ± 0.6 % ID/g) (Figure E-G). Analysis of ex-vivo bioluminescence data indicated heterogeneous osseous tumor involvement, with matching areas of [89Zr]DFO-YS5 tracer uptake (Figure H). Conclusion: Our results demonstrate successful CD46-targeted immunoPET imaging of multiple myeloma in a murine model. CD46-targeted imaging shows great potential for clinical translation as an imaging agent, theranostic platform, and companion biomarker in multiple myeloma. Acknowledgements: We would like to acknowledge pilot funding from the Stephen and Nancy Grand Multiple Myeloma Translational Initiative. References1. Spinnato, P., et al., Contrast enhanced MRI and 18F-FDG PET-CT in the assessment of multiple myeloma: A comparison of results in different phases of the disease. European Journal of Radiology, 2012. 81(12): p. 4013-4018.2. Sherbenou, D.W., et al., Antibody-drug conjugate targeting CD46 eliminates multiple myeloma cells. The Journal of clinical investigation, 2016. 126(12): p. 4640-4653.3. Wang, S., et al., Molecular imaging of prostate cancer targeting CD46 using immunoPET. Clinical Cancer Research, 2020.