Dual-radiolabeled gold nanoparticle SPECT probes to target and image cancer in vivo

Objectives The efficacy of surface-functionalized gold nanoparticles as dual-radiolabeled single photon emission computed tomography (SPECT) imaging probes was explored in vivo using a tumor-bearing mouse model.

Methods 10 nm diameter gold nanoparticles were surface functionalized with polyethylene glycol and a peptide that could be radiolabeled with both radiometals and radiohalogens. Nanoparticle suspensions were labeled with both In-111 and I-125, and radiochemical purity was evaluated with thin lay chromatography (TLC). Nanoprobes were injected via the tail vein into tumor-bearing nude mice. SPECT/X-ray CT imaging was performed after injection and 4, 24, and 48 hours later. 2 SPECT channels were used to track In-111 and I-125 individually; 28 ± 3 keV was used for I-125 and 200 ± 60 keV was used for In-111. Tumor uptake was quantified from 3D SPECT image reconstructions. After imaging, mice were sacrificed, and biodistribution studies were performed.

Results Dual-radiolabeled gold nanoparticles were synthesized by chelating In-111 to DTPA and reacting I-125 to tyrosine, with 100% radiochemical purity observed by TLC. After injection, both isotopes were co-registered in the blood pool. At later time points, I-125 was localized to the thyroid and stomach. In-111 was detected in the blood pool at both 4 hours and 24 hours. Tumor accumulation was visualized using In-111 at both 24 and 48 hours. Biodistribution studies correlated quantitatively with imaging, where tumor to muscle ratios of 8:1 were observed.

Conclusions Dual-radiolabeled gold nanoparticles offer multifunctional properties that make them promising for both imaging and therapeutic applications. Gold nanoparticles can be easily surface-functionalized with peptides and other molecules, which can be labeled with radiometals and radiohalogens in order to track multiple SPECT spectroscopic signals in vivo. Due to their size, renal clearance was avoided, providing long blood circulation, and therefore significant tumor accumulation through the enhanced permeability and retention (EPR) effect over a 48 hour period.

Research Support This work was supported by grants from the National Heart, Lung, and Blood Institute (NHLBI) Program of Excellence in Nanotechnology (HHSN268201000046C) and the Department of Defense (DOD) Breast Cancer Research Program (W81XWH-09-1-0333)