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Direct and Indirect Chimeric Antigen Receptor T-Cell Imaging with PET/MRI in a Tumor Xenograft Model.
Kim, Seog-Young; Soh, Hyunsu; Jung, Jin Hwa; Cho, Eun Hye; Kim, Hyori; Ju, Ji-Min; Sheen, Joong Hyuk; Lee, Sang Ju; Oh, Seung Jun; Lee, Sang-Jin; Chung, Junho; Ryu, Jin-Sook.
Afiliación
  • Kim SY; From the Convergence Medicine Research Center (S.Y.K., H.S., J.H.J., H.K.) and Department of Nuclear Medicine (E.H.C., Sang Ju Lee, S.J.O., J.S.R.), Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Research Institute, National Cancer Center, Gyeonggi-do, Republic
  • Soh H; From the Convergence Medicine Research Center (S.Y.K., H.S., J.H.J., H.K.) and Department of Nuclear Medicine (E.H.C., Sang Ju Lee, S.J.O., J.S.R.), Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Research Institute, National Cancer Center, Gyeonggi-do, Republic
  • Jung JH; From the Convergence Medicine Research Center (S.Y.K., H.S., J.H.J., H.K.) and Department of Nuclear Medicine (E.H.C., Sang Ju Lee, S.J.O., J.S.R.), Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Research Institute, National Cancer Center, Gyeonggi-do, Republic
  • Cho EH; From the Convergence Medicine Research Center (S.Y.K., H.S., J.H.J., H.K.) and Department of Nuclear Medicine (E.H.C., Sang Ju Lee, S.J.O., J.S.R.), Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Research Institute, National Cancer Center, Gyeonggi-do, Republic
  • Kim H; From the Convergence Medicine Research Center (S.Y.K., H.S., J.H.J., H.K.) and Department of Nuclear Medicine (E.H.C., Sang Ju Lee, S.J.O., J.S.R.), Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Research Institute, National Cancer Center, Gyeonggi-do, Republic
  • Ju JM; From the Convergence Medicine Research Center (S.Y.K., H.S., J.H.J., H.K.) and Department of Nuclear Medicine (E.H.C., Sang Ju Lee, S.J.O., J.S.R.), Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Research Institute, National Cancer Center, Gyeonggi-do, Republic
  • Sheen JH; From the Convergence Medicine Research Center (S.Y.K., H.S., J.H.J., H.K.) and Department of Nuclear Medicine (E.H.C., Sang Ju Lee, S.J.O., J.S.R.), Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Research Institute, National Cancer Center, Gyeonggi-do, Republic
  • Lee SJ; From the Convergence Medicine Research Center (S.Y.K., H.S., J.H.J., H.K.) and Department of Nuclear Medicine (E.H.C., Sang Ju Lee, S.J.O., J.S.R.), Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Research Institute, National Cancer Center, Gyeonggi-do, Republic
  • Oh SJ; From the Convergence Medicine Research Center (S.Y.K., H.S., J.H.J., H.K.) and Department of Nuclear Medicine (E.H.C., Sang Ju Lee, S.J.O., J.S.R.), Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Research Institute, National Cancer Center, Gyeonggi-do, Republic
  • Lee SJ; From the Convergence Medicine Research Center (S.Y.K., H.S., J.H.J., H.K.) and Department of Nuclear Medicine (E.H.C., Sang Ju Lee, S.J.O., J.S.R.), Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Research Institute, National Cancer Center, Gyeonggi-do, Republic
  • Chung J; From the Convergence Medicine Research Center (S.Y.K., H.S., J.H.J., H.K.) and Department of Nuclear Medicine (E.H.C., Sang Ju Lee, S.J.O., J.S.R.), Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Research Institute, National Cancer Center, Gyeonggi-do, Republic
  • Ryu JS; From the Convergence Medicine Research Center (S.Y.K., H.S., J.H.J., H.K.) and Department of Nuclear Medicine (E.H.C., Sang Ju Lee, S.J.O., J.S.R.), Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea; Research Institute, National Cancer Center, Gyeonggi-do, Republic
Radiology ; 310(2): e231406, 2024 02.
Article en En | MEDLINE | ID: mdl-38411517
ABSTRACT
Background Chimeric antigen receptor (CAR) T cells are a promising cancer therapy; however, reliable and repeatable methods for tracking and monitoring CAR T cells in vivo remain underexplored. Purpose To investigate direct and indirect imaging strategies for tracking the biodistribution of CAR T cells and monitoring their therapeutic effect in target tumors. Materials and Methods CAR T cells co-expressing a tumor-targeting gene (anti-CD19 CAR) and a human somatostatin receptor subtype 2 (hSSTr2) reporter gene were generated from human peripheral blood mononuclear cells. After direct labeling with zirconium 89 (89Zr)-p-isothiocyanatobenzyl-desferrioxamine (DFO), CAR T cells were intravenously injected into immunodeficient mice with a CD19-positive and CD19-negative human tumor xenograft on the left and right flank, respectively. PET/MRI was used for direct in vivo imaging of 89Zr-DFO-labeled CAR T cells on days 0, 1, 3, and 7 and for indirect cell imaging with the radiolabeled somatostatin receptor-targeted ligand gallium 68 (68Ga)-DOTA-Tyr3-octreotide (DOTATOC) on days 6, 9, and 13. On day 13, mice were euthanized, and tissues and tumors were excised. Results The 89Zr-DFO-labeled CAR T cells were observed on PET/MRI scans in the liver and lungs of mice (n = 4) at all time points assessed. However, they were not visualized in CD19-positive or CD19-negative tumors, even on day 7. Serial 68Ga-DOTATOC PET/MRI showed CAR T cell accumulation in CD19-positive tumors but not in CD19-negative tumors from days 6 to 13. Notably, 68Ga-DOTATOC accumulation in CD19-positive tumors was highest on day 9 (mean percentage injected dose [%ID], 3.7% ± 1.0 [SD]) and decreased on day 13 (mean %ID, 2.6% ± 0.7) in parallel with a decrease in tumor volume (day 9 mean, 195 mm3 ± 27; day 13 mean, 127 mm3 ± 43) in the group with tumor growth inhibition. Enhanced immunohistochemistry staining of cluster of differentiation 3 (CD3) and hSSTr2 was also observed in excised CD19-positive tumor tissues. Conclusion Direct and indirect cell imaging with PET/MRI enabled in vivo tracking and monitoring of CAR T cells in an animal model. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Bulte in this issue.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Quiméricos de Antígenos / Neoplasias Límite: Animals / Humans Idioma: En Revista: Radiology Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Quiméricos de Antígenos / Neoplasias Límite: Animals / Humans Idioma: En Revista: Radiology Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos