DOI QR코드

DOI QR Code

Evaluation of Therapeutic Monitoring of Prostate Cancer (PCa) using [18F]Florastamin, Diagnostic Radiopharmaceutical for PCa: Non-clinical Ex vivo Whole-body Autoradiographic Analysis

  • Min Hwan Kim (Research Institute of Radiopharmaceuticals, FutureChem Co., Ltd.) ;
  • Kyongkyu Lee (Research Institute of Radiopharmaceuticals, FutureChem Co., Ltd.) ;
  • Hee Seup Kil (Research Institute of Radiopharmaceuticals, FutureChem Co., Ltd.) ;
  • Soon Jeong Kwon (Research Institute of Radiopharmaceuticals, FutureChem Co., Ltd.) ;
  • Yong Jin Lee (Division of Applied RI, Korea Institute of Radiological & Medical Sciences) ;
  • Kyo Chul Lee (Division of Applied RI, Korea Institute of Radiological & Medical Sciences) ;
  • Dae Yoon Chi (Research Institute of Radiopharmaceuticals, FutureChem Co., Ltd.)
  • Received : 2023.06.12
  • Accepted : 2023.06.13
  • Published : 2023.06.30

Abstract

In this study, we evaluated the targeting of prostate cancer (PCa) using [18F]Florastamin in non-clinical study, for the purpose of therapeutic monitoring of [177Lu]Ludotadipep, a therapeutic radiopharmaceutical for PCa, [18F]Florastamin/[177Lu]Ludotadipep was co-administered to a single-individual prostate tumor bearing mouse model, mimicking clinical condition. Considering the difference in half-life of the two isotopes (18F or 177Lu), image scan of whole-body autoradiography was performed at 24 or 48 h after preparation of frozen section, respectively. Then, it was confirmed whether they showed the same targeting efficiency for the area of tumor. A tumor xenograft model was prepared using PSMA-overexpressing PC3-PIP prostate cancer cells. [18F]Florastamin [111 MBq (3 mCi) in 100 µL]/177Lu]Ludotadipep [3.7 MBq (100 µCi) in 100 µL] was co-administered through the tail vein, and 2 hours after administration, the mice were frozen, and after freezing for 24 hours, whole-body cryosection was performed at 24 h after freezing. Image scanning using cryosection was performed after 24 or 48 hours after freezing, respectively. In the scan image after 24 hours, tumor uptake of [18F] Florastamin/[177Lu]Ludotadipep were simultaneously observed specific uptake in the tumor. In the scan image after 48 hours in the same section, signal of 18F was lost by decay of radioisotope, and specific uptake image for [177Lu]Ludotadipep was observed in the tumor. Uptake of [177Lu]Ludotadipep was specific to the same tumor region where [18F]Florastamin/[177Lu]Ludotadipep was uptake. These results suggested that [18F]Florastamin showed the same tumor uptake efficiency to PCa as [177Lu]Ludotadipep, and effective therapeutic monitoring is expected to be enable using [18F]Florastamin during [177Lu]Ludotadipep therapy for PCa.

Keywords

Acknowledgement

이 논문은 한국연구재단 원자력연구개발사업/방사성동위원소산업 육성 및 고도화 지원사업/수요 맞춤형 동위원소 생산 직접화 및 시설 고도화(NRF-2021M2E7A1079168)과 과학기술정보통신부 한국원자력의학원 연구운영비지원사업(50461-2023)의 지원에 의하여 이루어졌으며 다른 이해관계는 없음을 밝힙니다.

References

  1. Perner S, Hofer MD, Kim R, Shah RB, Li H, Moller P, Hautmann RE, Gschwend JE, Kuefer R, Rubin MA. Prostate-specific membrane antigen expression as a predictor of prostate cancer progression. Hum Pathol 2007;38:696-701. https://doi.org/10.1016/j.humpath.2006.11.012
  2. 최석환.권태균 전립선암 선별검사로서 PSA의 유용성. Korean J Urol Oncol 2013;11:1-5.
  3. Teo MY, Rathkopf DE, Kantoff P. Treatment of Advanced Prostate Cancer. Annu Rev Med 2019;70:479-99. https://doi.org/10.1146/annurev-med-051517-011947
  4. Vellky JE, Ricke WA. Development and prevalence of castration-resistant prostate cancer subtypes. Neoplasia 2020;22:566-75. https://doi.org/10.1016/j.neo.2020.09.002
  5. Fendler WP, Rahbar K, Herrmann K, Kratochwil C, Eiber M. 177Lu-PSMA Radioligand Therapy for Prostate Cancer. J Nucl Med 2017;58(8):1196-200. https://doi.org/10.2967/jnumed.117.191023
  6. Wester HJ, Schottelius M. PSMA-Targeted Radiopharmaceuticals for Imaging and Therapy. Semin Nucl Med 2019;49:302-12. https://doi.org/10.1053/j.semnuclmed.2019.02.008
  7. Seifert R, Alberts IL, Afshar-Oromieh A, Rahbar K. Prostate Cancer Theranostics: PSMA Targeted Therapy. PET Clin 2021;16:391-6. https://doi.org/10.1016/j.cpet.2021.03.004
  8. Hennrich U, Eder M. [68Ga]Ga-PSMA-11: The First FDA-Approved 68Ga-Radiopharmaceutical for PET Imaging of Prostate Cancer. Pharmaceuticals (Basel) 2021;14:713.
  9. FDA Announces Priority Review of 18F-DCFPyL NDA. J Nucl Med 2021;62:21N-22N.
  10. Lee BS, Chu SY, Jung WJ, Jeong HJ, Lee K, Kim MH, Kim MH, Chi DY, Ahn H, Lee YJ, Lee KC, Lim SM. 18F-labeled 1,2,3-triazole-linked Glu-urea-Lys-based PSMA ligands have good pharmacokinetic properties for positron emission tomography imaging of prostate cancer. Prostate 2020;80:1383-93. https://doi.org/10.1002/pros.24062
  11. Kabasakal L, Toklu T, Yeyin N, Demirci E, Abuqbeitah M, Ocak M, Aygun A, Karayel E, Pehlivanoglu H, Alan Selcuk N. Lu-177-PSMA-617 Prostate-Specific Membrane Antigen Inhibitor Therapy in Patients with Castration-Resistant Prostate Cancer: Stability, Biodistribution, and Dosimetry. Mol Imaging Radionucl Ther 2017;26:62-8. https://doi.org/10.4274/mirt.08760
  12. Wrenger R, Juptner M, Marx M, Zhao Y, Zuhayra M, Caliebe A, Osmonov D, Lutzen U. Pre- and intratherapeutic predictors of overall survival in patients with advanced metastasized castration-resistant prostate cancer receiving Lu-177-PSMA-617 radioligand therapy. BMC Urol 2022;22:96.
  13. Schneider CA, Tager P, Hammes J, Fischer T, Drzezga A, Pfister D, Heidenreich A, Schmidt M. Treatment outcome and identification of factors influencing overall survival after Lu-177-PSMA-617 radioligand therapy in metastatic prostate cancer. Nuklearmedizin 2022;61:25-32. https://doi.org/10.1055/a-1670-9500
  14. Hennrich U, Eder M. [177Lu]Lu-PSMA-617 (PluvictoTM): The First FDA-Approved Radiotherapeutical for Treatment of Prostate Cancer. Pharmaceuticals (Basel) 2022;15:1292.
  15. Kelly JM, Amor-Coarasa A, Ponnala S, Nikolopoulou A, Williams C Jr, DiMagno SG, Babich JW. Albumin-Binding PSMA Ligands: Implications for Expanding the Therapeutic Window. J Nucl Med 2019;60:656-63. https://doi.org/10.2967/jnumed.118.221150
  16. Wang Z, Tian R, Niu G, Ma Y, Lang L, Szajek LP, Kiesewetter DO, Jacobson O, Chen X. Single Low-Dose Injection of Evans Blue Modified PSMA-617 Radioligand Therapy Eliminates Prostate-Specific Membrane Antigen Positive Tumors. Bioconjug Chem 2018;29:3213-21. https://doi.org/10.1021/acs.bioconjchem.8b00556
  17. Deberle LM, Tschan VJ, Borgna F, Sozzi-Guo F, Bernhardt P, Schibli R, Muller C. Albumin-Binding PSMA Radioligands: Impact of Minimal Structural Changes on the Tissue Distribution Profile. Molecules 2020;25:2542.
  18. Kramer V, Fernandez R, Lehnert W, Jimenez-Franco LD, Soza-Ried C, Eppard E, Ceballos M, Meckel M, Benesova M, Umbricht CA, Kluge A, Schibli R, Zhernosekov K, Amaral H, Muller C. Biodistribution and dosimetry of a single dose of albumin-binding ligand [177Lu]Lu-PSMA-ALB-56 in patients with mCRPC. Eur J Nucl Med Mol Imaging 2021;48:893-903. https://doi.org/10.1007/s00259-020-05022-3
  19. Lee BS, Kim MH, Chu SY, Jung WJ, Jeong HJ, Lee K, Kim HS, Kim MH, Kil HS, Han SJ, Lee YJ, Lee KC, Lim SM, Chi DY. Improving Theranostic Gallium-68/Lutetium-177-Labeled PSMA Inhibitors with an Albumin Binder for Prostate Cancer. Mol Cancer Ther 2021;20:2410-9. https://doi.org/10.1158/1535-7163.MCT-21-0251