Centre for Advanced Biomedical Imaging (CABI), Department of Medicine, University College London, London WC1E 6DD, UK.
Healthcare Biomagnetics Laboratory, University College London, 21 Albemarle Street, London, W1S 4BS, UK.
Nanoscale. 2024 Oct 31;16(42):19715-19729. doi: 10.1039/d4nr00240g.
Magnetic field hyperthermia relies on the intra-tumoural delivery of magnetic nanoparticles by interstitial injection, followed by their heating on exposure to a remotely-applied alternating magnetic field (AMF). This offers a potential sole or adjuvant route to treating drug-resistant tumours for which no alternatives are currently available. However, two challenges in nanoparticle delivery currently hinder the effective clinical translation of this technology: obtaining enough magnetic material within the tumour to enable sufficient heating; and doing this accurately to limit or avoid damage to surrounding healthy tissue. A further complication is the lack of established methods to non-invasively quantify nanoparticle biodistribution, which is necessary to evaluate the performance of improved delivery strategies. Here we employ In radiolabelling and single-photon emission computed tomography (SPECT) to non-invasively quantify distribution of a clinical grade iron-oxide-based nanoparticle in a mouse model of melanoma. We show that compared to manual injection, ultrasound guided delivery together with syringe-pump-controlled infusion improves both the nanoparticle concentration within the tumour, and the accuracy of delivery - reducing off-target peri-tumoural delivery. Following AMF heating, injected melanomas shrank significantly compared to non-injected controls, validating therapeutic efficacy. Systemic off-target delivery was quantified and extrapolated to predict off-target energy absorbance within safe limits for the main sites of background accumulation. With many nanoparticle-based therapies currently in development for cancer, this image-guided delivery strategy has wide potential impact beyond the field of magnetic hyperthermia. Future use in representative patient cohorts would also be enabled by the high clinical availability of both SPECT and ultrasound imaging.
磁场热疗依赖于间质内注射将磁性纳米粒子递送至肿瘤内，然后在暴露于远程施加的交变磁场（AMF）时对其进行加热。这为治疗目前尚无替代方法的耐药肿瘤提供了一种潜在的单一或辅助治疗途径。然而，目前在纳米颗粒递送上有两个挑战阻碍了该技术的有效临床转化：在肿瘤内获得足够的磁性材料以实现足够的加热；并且要做到这一点的准确性，以限制或避免对周围健康组织的损伤。另一个复杂的问题是缺乏建立的方法来非侵入性地量化纳米颗粒的生物分布，这对于评估改进的递药策略的性能是必要的。在这里，我们使用放射性标记和单光子发射计算机断层扫描（SPECT）来非侵入性地量化铁氧化物基纳米颗粒在黑色素瘤小鼠模型中的分布。我们表明，与手动注射相比，超声引导输送结合注射器泵控制输注可提高肿瘤内的纳米颗粒浓度和输送的准确性，从而减少肿瘤周围的非靶向输送。在 AMF 加热后，与未注射对照相比，注射的黑色素瘤明显缩小，验证了治疗效果。量化了系统的非靶向输送，并外推预测了在主要背景积累部位的安全范围内的非靶向能量吸收。随着许多基于纳米颗粒的癌症治疗方法目前正在开发中，这种图像引导的输送策略除了在磁场热疗领域之外，具有广泛的潜在影响。通过 SPECT 和超声成像的高临床可用性，也将能够在代表性的患者队列中使用该策略。
