Rice Samuel L, Muñoz Fernando Gómez, Benjamin Jamaal, Kim Seung, Park Auh Whan, Osborne Joseph R, Beets-Tan Regina
Department of Radiology, Netherlands Cancer Institute- Antoni van Leeuwenhoekziekenhuis, Plesmanlaan 121, Amsterdam, 1066 CX Netherlands.
Department of Radiology, Interventional Radiology Section, UT Southwestern Medical Center, 5959 Harry Hines Blvd., Professional Office Building I (HP6.600) Mail Code, Dallas, TX 75390-9061, 8834 USA.
Nucl Med Mol Imaging. 2025 Aug;59(4):217-228. doi: 10.1007/s13139-024-00892-z. Epub 2024 Nov 21.
Directed therapies employing small (SM) and large (LM) molecule drugs to target tumor antigens are used for treatment. Theranostics radiolabels them for imaging and radiation treatment. Poor radiopharmaceutical kinetics, prolonged circulating times, and high nontarget radiation to normal tissues after intravenous (i.v) injection limits translation. Intra-arterial (i.a.) procedures locally concentrate nonspecific chemotherapies or radiation to treat hepatic tumors (HT). Pseudovascular isolation (PVI), embolizes the HT arterioles, blocking efferent flow into capillaries isolating the HT from the systemic vasculature maximizing uptake to provide curative tumor specific absorbed radiation.
[¹⁸F]Fluorodeoxyglucose (FDG) SM and Tc-labeled macroaggregated albumin (MAA) LM surrogates were used to assess biodistribution in a porcine HT. Injected dose per gram (%ID/g) of the tracers obtained from 1 to 120 min after control (i.v) and experimental i.a. infusion with PVI.
SM drug delivered to HT was 290-366% greater for PVI vs. i.v (60 min %ID/g 31.26 ± 2.55 vs. 8.83 ± 0.55, = 0.033; 120 min 29.28 ± 1.44 vs. 8.94 ± 0.96, = 0.145). Mean HT uptake of LM with PVI was up to 760% greater than i.v. without washout (60 min %ID/g 80.01 ± 2.87 vs. 10.61 ± 0.96 = 0.001; 81.72 ± 3.0 vs. 11.98 ± 0.3 = 0.001 at 120 min).
PVI significantly increases the concentration of both SM and LM drugs within a HT compared to i.v. infusion. PVI with tumor specific drugs offers an opportunity to locally cure HT using a drug that specifically targets tumor antigens.
采用小分子（SM）和大分子（LM）药物靶向肿瘤抗原的定向疗法用于治疗。治疗诊断学用放射性标记物标记它们以进行成像和放射治疗。静脉内（i.v.）注射后放射性药物动力学不佳、循环时间延长以及对正常组织的高非靶向辐射限制了其转化应用。动脉内（i.a.）操作可将非特异性化疗药物或辐射局部集中用于治疗肝肿瘤（HT）。假血管隔离（PVI）可栓塞肝肿瘤小动脉，阻断流入毛细血管的传出血流，使肝肿瘤与全身血管系统隔离，从而使摄取最大化，以提供治愈性的肿瘤特异性吸收辐射。
使用[¹⁸F]氟脱氧葡萄糖（FDG）小分子替代物和锝标记的大颗粒白蛋白（MAA）大分子替代物评估猪肝肿瘤中的生物分布。在对照（i.v.）和采用PVI的实验性动脉内输注后1至120分钟获得示踪剂的每克注射剂量（%ID/g）。
与静脉内注射相比，PVI使输送到肝肿瘤的小分子药物增加290 - 366%（60分钟时%ID/g为31.26±2.55对8.83±0.55，P = 0.033；120分钟时为29.28±1.44对8.94±0.96，P = 0.145）。采用PVI时大分子在肝肿瘤中的平均摄取比静脉内注射且无洗脱时高出多达760%（60分钟时%ID/g为80.01±2.87对10.61±0.96，P = 0.001；120分钟时为81.72±3.0对11.98±0.3，P = 0.001）。
与静脉内输注相比，PVI可显著提高肝肿瘤内小分子和大分子药物的浓度。使用肿瘤特异性药物的PVI为使用特异性靶向肿瘤抗原的药物局部治愈肝肿瘤提供了机会。
