Multimodality imaging of naturally active melanin nanoparticles targeting somatostatin receptor subtype 2 in human small-cell lung cancer

Abstract

Somatostatin receptor subtype 2 (SSTR₂) is highly expressed in pulmonary neuroendocrine tumors, which account for approximately 25% of all lung cancers including small-cell lung cancer (SCLC). It is possible to establish SCLC-specific imaging agents for multimodal imaging to obtain tumor integrity information. Herein, we constructed novel multifunctional organic melanin nanoparticles (MNPs) as a carrier and surface-loaded somatostatin analog octreotide to produce a human small-cell lung cancer-targeted nanoprobe OCT-PEG-MNPs. MNPs have an excellent photoacoustic imaging (PAI) function and can be directly chelated with the magnetic resonance contrast agent Mn²⁺, and N-bromo succinimide (NBS) can be used as an oxidant to label the nanoparticles with the long half-life radionuclide ¹²⁴I by an electrophilic substitution reaction. Therefore, (¹²⁴I, Mn) OCT-PEG-MNPs can not only be used for PAI but also be used for positron emission tomography (PET) and magnetic resonance imaging (MRI). The NCI-H69 SCLC tumor xenograft model with high SSTR₂ expression was constructed to evaluate the multimodal imaging ability of (¹²⁴I, Mn) OCT-PEG-MNPs. This nanoprobe showed good imaging abilities in PAI, MRI and PET. The PA images showed that the photoacoustic signal in the NCI-H69 tumor site gradually increased with time, and the NCI-H69 xenograft showed a clear increase in the T₁-weighted signal intensity after injection of Mn-OCT-PEG-MNPs at 24 h compared to that in the prescan. MicroPET and biodistribution studies showed that the uptake of NCI-H69 tumors (8.03 ± 0.37% ID g⁻¹) was significantly higher than that in the control A549 model (3.35 ± 0.54% ID g⁻¹) after injection of (¹²⁴I, Mn) OCT-PEG-MNPs at 24 h. The (¹²⁴I, Mn) OCT-PEG-MNPs were successfully applied to multimodal imaging in a small-cell lung cancer model with high SSTR₂ expression. This nanoprobe may be considered for clinical trials since it combines the numerous advantages of organic nanoparticles.