PET and MR imaging with 64Cu/68Ga-labeled AGuIX ultra-small nanoparticles in tumor-bearing mice

1181 Objectives To determine tumor targeting by MRI and PET imaging with ultra-small gadolinium-based nanoparticles, AGuIX, AGuIX-68Ga and AGuIX-NODA-64Cu, in a 4T1 murine breast cancer model. These particles have capabilities to radiosensitive tumors prior to external beam irradiation, and therefore imaging will assist in guiding radiation therapy. Methods Radiolabeling conditions for ultra-small nanoparticles with either 68Ga or 64Cu were optimized for small animal PET imaging. Ten female BALB/c mice were injected subcutaneously above the right shoulder with 1 x 105 4T1 cells and allowed to grow to ~100-500 mm3. Two mice were imaged by MRI immediately after tail vein injection of unlabeled AGuIX nanoparticles. Four mice were imaged by PET/CT at 1, 2, 4, 24 h after injection with AGuIX-NODA-64Cu. And four mice were imaged by PET/CT at 1, 2, 4 h after injection with AGuIX-68Ga. Biodistribution studies were done at the 24 h and 4 h time point for mice injected with AGuIX-NODA-64Cu and AGuIX-68Ga, respectively. Results The radiolabeling yields of these ultra-small nanoparticles were 81-85%. T1-weighted MRI of tumors following i.v. injection showed fast accumulation (within 10 min p.i.) and slow diffusion out of the tumor (over 30 min p.i.). The PET images showed significant accumulation in the tumor, 3.00 ± 0.53% ID/g for AGuIX-NODA-64Cu 24 h p.i. and for 4.59 ± 1.02% ID/g AGuIX-68Ga 4 h p.i. Measurement of radioactivity in major organs ex vivo of AGuIX-NODA-64Cu 24h p.i. gave tumor:muscle ratios of 10.42, and the SUVmax was 2.56. For AGuIX-NODA-64Cu, the kidney had the highest non-target tissue uptake (55.9%ID/gmax at 24 h), with relatively low liver and muscle uptake (4.17 and 0.71%ID/gmax at 24 h, respectively). Conclusions Radiolabeling conditions are being optimized to increase radiochemical yield. The MR images with AGuIX and PET with AGuIX-NODA-64Cu and AGuIX-68Ga nanoparticles showed accumulation in tumors with renal clearance. Optimal nanoparticle uptake into the tumors was from 1 to 4 h post injection as determined by PET/CT imaging. SUPPORT: DOE DE SC0008833, NCI P30CA047904, and S10 RR025098.