Vipivotide tetraxetan (PSMA-617) is a synthetic ligand molecule that targets the prostate-specific membrane antigen (PSMA; Ki=0.3nM)[1-2]. Vipivotide tetraxetan can be chelated with 68G or 177Lu for the diagnosis and targeted therapy research of metastatic castration-resistant prostate cancer (mCRPC)[3-4].
In vitro, PC3-PSMA and LNCaP prostate cancer cell lines were pretreated with 5-aza-2'-deoxycytidine (5-aza-dC) and valproic acid (VPA) for 5 days, followed by co-incubation with ¹⁷⁷Lu-chelated Vipivotide tetraxetan (50kBq/1 mL) for 1-24 hours. 5-aza-dC and VPA significantly increased the cellular uptake of Vipivotide tetraxetan[5]. PSMA-positive PC-3 PIP tumor cells were treated with ¹⁶¹Tb- or ¹⁷⁷Lu-labeled Vipivotide tetraxetan (0.1-10MBq/mL) for 4 hours. ¹⁶¹Tb- or ¹⁷⁷Lu-labeled Vipivotide tetraxetan significantly reduced cell viability and survival[6].
In vivo, BALB/c nude mice bearing HepG2 hepatocellular carcinoma xenografts were treated with a single intravenous injection of ¹⁷⁷Lu-labeled Vipivotide tetraxetan (37MBq per mouse). ¹⁷⁷Lu-labeled Vipivotide tetraxetan significantly inhibited tumor growth and prolonged the survival of the tumor-bearing mice[7]. BALB/cAnNRj mice were treated with a single intravenous injection of ¹⁷⁷Lu-labeled Vipivotide tetraxetan (120, 160, or 200MBq per mouse). ¹⁷⁷Lu-labeled Vipivotide tetraxetan caused transient hematological toxicity (including decreased counts of white blood cells, red blood cells, and platelets) but did not cause death[8].
References:
[1] Benešová M, Schäfer M, Bauder-Wüst U, et al. Preclinical Evaluation of a Tailor-Made DOTA-Conjugated PSMA Inhibitor with Optimized Linker Moiety for Imaging and Endoradiotherapy of Prostate Cancer. J Nucl Med. 2015 Jun;56(6):914-20.
[2] Ruigrok EAM, van Vliet N, Dalm SU, et al. Extensive preclinical evaluation of lutetium-177-labeled PSMA-specific tracers for prostate cancer radionuclide therapy. Eur J Nucl Med Mol Imaging. 2021 May;48(5):1339-1350.
[3] Han XD, Liu C, Liu F, et al. 64Cu-PSMA-617: A novel PSMA-targeted radio-tracer for PET imaging in gastric adenocarcinoma xenografted mice model. Oncotarget. 2017 May 26;8(43):74159-74169.
[4] Vilangattil MM, Swaidan A, Godinez J, et al. Hematological toxicity of [225Ac]Ac-PSMA-617 and [177Lu]Lu-PSMA-617 in RM1-PGLS syngeneic mouse model. EJNMMI Radiopharm Chem. 2025 Mar 24;10(1):12.
[5] Runge R, Naumann A, Miederer M, et al. Up-Regulation of PSMA Expression In Vitro as Potential Application in Prostate Cancer Therapy. Pharmaceuticals (Basel). 2023 Apr 4;16(4):538.
[6] Müller C, Umbricht CA, Gracheva N, et al. Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer. Eur J Nucl Med Mol Imaging. 2019 Aug;46(9):1919-1930.
[7] Lu Q, Long Y, Gai Y, et la. [177Lu]Lu-PSMA-617 theranostic probe for hepatocellular carcinoma imaging and therapy. Eur J Nucl Med Mol Imaging. 2023 Jul;50(8):2342-2352.
[8] Kristiansson A, Vilhelmsson Timmermand O, Altai M, et al. Hematological Toxicity in Mice after High Activity Injections of 177Lu-PSMA-617. Pharmaceutics. 2022 Mar 28;14(4):731.
Vipivotide tetraxetan (PSMA-617)是一种靶向前列腺特异性膜抗原（PSMA；Ki=0.37nM）的合成配体分子[1-2]。Vipivotide tetraxetan可与68Gu或177Lu螯合，用于PSMA阳性转移性去势抵抗性前列腺癌（mCRPC）的诊断与靶向治疗研究[3-4]。
在体外，5-aza-2‘-deoxycytidine （5-aza-dC）和valproic acid（VPA）预处理PC3-PSMA和LNCaP前列腺癌细胞系5天，随后与177Lu螯合的Vipivotide tetraxetan（50kBq/1mL）共孵育1-24小时，5-aza-dC和VPA显著增加了Vipivotide tetraxetan的细胞摄取[5]。¹⁶¹Tb或¹⁷⁷Lu标记的Vipivotide tetraxetan（0.1-10MBq/mL）处理PSMA阳性的PC-3 PIP肿瘤细胞4小时。¹⁶¹Tb或¹⁷⁷Lu标记的Vipivotide tetraxetan显著降低细胞活力与存活[6]。
在体内，¹⁷⁷Lu标记的Vipivotide tetraxetan（37MBq/只）通过尾静脉单次注射处理携带HepG2肝细胞癌异种移植瘤的BALB/c裸鼠。¹⁷⁷Lu标记的Vipivotide tetraxetan能显著抑制肿瘤生长并延长荷瘤小鼠的生存期[7]。¹⁷⁷Lu标记的Vipivotide tetraxetan（120，160，200MBq/只）通过尾静脉单次注射处理BALB/cAnNRj小鼠。¹⁷⁷Lu标记的Vipivotide tetraxetan能引起小时暂时性的血液毒性（包括白细胞、红细胞和血小板计数的下降），但不会引起死亡[8]。