-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

1935 Preclinical In Vivo Imaging of Multiple Myeloma with [18f]Fluorohomoleucine (FHL) PET/CT

Program: Oral and Poster Abstracts
Session: 651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational: Poster I
Hematology Disease Topics & Pathways:
Research, Translational Research, Diseases
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Milena Colovic, PhD1,2*, Matthew Nodwell, PhD3*, Leo Escano, BS4*, Nadine Colpo5*, Ingrid Bloise, MD5*, Gokce Engudar, PhD6*, Helen Merkens7*, Francois Benard, MD8*, Paul Schaffer, PhD9*, Florian Kuchenbauer, MD, PhD, FRCPC10 and Robert Britton, PhD11*

1Life Sciences Division, TRIUMF, Vancouver, BC, Canada
2Molecular Oncology, BC Cancer, Vancouver, BC, Canada
3Simon Fraser University, Burnaby, BC, Canada
4Terry Fox Laboratory, British Columbia Cancer Research Institute, Vancouver, Canada
5BC Cancer, Vancouver, Canada
6Life Sciences Division, TRIUMF, Vancouver, Canada
7Molecular Oncology, BC Cancer, Vancouver, Canada
8BC Cancer, Vancouver, BC, CAN
9TRIUMF, Vancouver, BC, Canada
10BC Cancer Research Centre, Vancouver, BC, Canada
11Simon Fraser University, Burnaby, Canada

Purpose: Imaging of patients with multiple myeloma (MM) remains challenging due to its multi-focal nature affecting bone marrow, bone structures and soft tissue. As a result, current diagnostic methods like X-rays, CT and MRI scans only provide a partial understanding of disease activity and treatment response, lacking a comprehensive overview. Although 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) has become the standard for detecting multifocal cancer spread, its use in MM patients is limited due to metabolic heterogeneity of MM and limited sensitivity in detecting extramedullary disease leading to false negative and false positive scans. To overcome these limitations, we developed a novel radiopharmaceutical L-[18F]Fluorohomoleucine (FHL) targeting LAT1 amino acid transporter. LAT1 has been significantly correlated with the proliferative activity of MM cells, poor prognosis and response to treatment in MM patients, presenting an appealing molecular target for assessing disease activity.

Methods: FHL was synthesized as described by Nodwell et al. (J Nucl Med, 2019) and FDG was obtained from BC Cancer. LAT1 expression in multiple myeloma (MM) cell lines was confirmed by flow cytometry. Cell uptake assays were conducted using luciferase-transfected MM1S, L363, NCI H929 and AMO1 MM cells, and 2-amino-bicyclo[2.2.1]heptanes-2-carboxylic acid (BCH) was used as a blocking agent. For in vivo studies, male NRG mice were injected either with 1 x 106 MM cells intravenously (i.v.) via the caudal vein or subcutaneously (SQ) with 1 x 107 cells. Tumor engraftment was monitored weekly on an in vivo bioluminescence imager Perkin Elmer’s IVIS Ilumina 5, starting at 2 weeks post-injection (p.i.). Biodistribution and PET/CT imaging studies were conducted at 4-6 weeks p.i.

Results: All MM cells tested exhibited LAT1-specific FHL uptake in vitro, with L363 and NCI H929 demonstrating the highest tracer uptake and average blocking efficacy over 83% and 93%, respectively. We were able to observe weekly progression of disease in the i.v. cohort using IVIS imaging. Biodistribution and PET imaging studies revealed FHL accumulation in the SQ xenografts, pancreas and excretion via the urinary tract. The SQ tumor uptake values were 4.53±0.82 %ID/g in AMO1 xenografts, 5.55±0.82 %ID/g in NCI H929, and 6.37±0.70 %ID/g in L363 tumors. In the i.v. cohort, the mouse intravenously injected with L363 cells demonstrated accumulation of radioactivity in the skull and vertebrae, as anticipated from the IVIS images. Furthermore, preliminary data suggests that FHL was able to detect a more extensive bone and lymphatic involvement than FDG in MM xenografts.

Conclusion: We have demonstrated the ability of FHL for in vivo imaging of three human multiple myeloma tumors in SQ murine models, with the tumor uptake ranging from 4.53±0.82 %ID/g in AMO1 xenografts to 6.37±0.70 %ID/g in L363 tumors. Work is underway to establish the utility of this tracer in detecting disease dissemination in the orthotopic murine models of multiple myeloma, with promising preliminary results presented herein.

Disclosures: Benard: Alpha-9 Theranostics: Membership on an entity's Board of Directors or advisory committees. Schaffer: ARTMS Inc: Consultancy.

*signifies non-member of ASH