Abstract
1144
Objectives To provide access to the somatostatin-receptor-targeting 68Ga-DOTA-NOC radiopharmaceutical for use in clinical PET/CT evaluation of neuroendocrine tumor patients being considered for multivisceral transplant.
Methods An Expanded Access IND was developed for 68Ga-DOTA-NOC, an agent that has had extensive world-wide use in neuroendocrine tumor imaging, but which is not available as an FDA-approved drug product in the United States. The 68Ga3+ was obtained in 1.5 mL 0.1M ultrapure HCL by fractionated elution of a TiO2-based 68Ge/68Ga generator system (Eckert & Ziegler); buffered by addition of ultrapure aqueous NaOAc; and reacted with commercial cGMP DOTA-NOC conjugate (60 µg) at 80°C for 10-minutes. The 68Ga-DOTA-NOC product was then isolated by C18 solid phase extraction; recovered in 0.6 mL 85% ethanol:15% saline; and diluted with additional sterile saline (12 mL) prior to terminal sterilizing filtration into a sterile evacuated vial. Quality control measures and release criteria followed the specifications of the published EANMMI Procedure Guidelines for such 68Ga-agents (Eur J Nucl Med Mol Imaging 37:2004-2010; 2010).
Results The 68Ga-DOTA-NOC radiopharmaceutical has been prepared for PET/CT imaging in 36 patients (administered dose: 4.7 ± 0.6 mCi; 174 ± 22 MBq). Total synthesis time, from generator elution to post-QC release of final sterile product, averaged 46 ± 5 minutes, with a product radiochemical purity of 98.1 ± 0.7%. 68Ge breakthrough in the final product has been at or near the background count rate, averaging 3.1 ± 3.8 x 10-7% at dose expiration.
Conclusions The manual synthesis approach has been effective for 68Ga-DOTA-NOC production, addressing a local clinical need in imaging assessment of the location and extent of disease in neuroendocrine cancer patients being considered for surgery.