The Cancer Imaging Program has been creating Investigational New Drug Applications (IND) for imaging agents in order to engage in multi-center clinical trials of these materials. A subset of the documents filed is being made available to the research community to implement routine synthesis of tracers at their own facilities and to assist investigators with the filing of their own INDs. Three document sets are currently available: F-18 fluorothymidine (FLT), [18F]Fluoromisonidazole, 1H-1-(3-[18F]-Fluoro-2-Hydroxy-Propyl)-2-Nitro-Imidazole, [18F]FMISO and 16-α-[18F]Fluoroestradiol.

Component Documents for an IND for 3'-deoxy-3'-[F-18]fluorothymidine: [F-18]FLT

These documents include a full set of manufacturing and QC documents and an Investigator Drug Brochure, all of which have been accepted by the FDA as part of the NCI IND. The synthetic method implemented in these documents was reported in an abstract by Blocher, A. et al., Procedure for Routine Synthesis of [18F] FLT in High Activities. J. Nucl. Med; 42 (5), 257P, 2001. An automated synthesis has been reported recently by the same group using the same precursor: Reischl, G., et al., Simplified, automated synthesis of 3'[18F]fluoro-3'-deoxy-thymidine ([18F]FLT) and simple method for metabolite analysis in plasma. Radiochim Acta, 2006. 94: p. 447-451. Investigators at each site can implement the synthesis and testing in their radiochemistry laboratory. There is a CMC template that may need to be modified to match the local procedures (e.g. specific brands of equipment). Investigators can then write and file their own IND with the FDA by modifying the CMC section to fit local conditions and adding the Investigator's proposed Clinical protocol, and NCI will provide a letter to cross-reference the NCI IND file at FDA for pharmacology, toxicology, dosimetry, and previous human experience. You may wish to consult these FLT Frequently Asked Questions before going forward.
FLT Transfer Agreement

Component documents for an IND for [18F]Fluoromisonidazole, 1H-1-(3-[18F]-Fluoro-2-Hydroxy-Propyl)-2-Nitro-Imidazole, [18F]FMISO

These documents include a full set of manufacturing and QC documents and an Investigator Drug Brochure, all of which have been accepted by the FDA as part of the NCI IND. The synthesis procedure follows that reported by Lim and Berridge (1993), An efficient radiosynthesis of [18F]fluoromisonidazole. Appl. Radiat. Isot. 44, 1085-1091. Investigators at each site can implement the synthesis and testing in their radiochemistry laboratory. There is a CMC template that will need to be modified to match the local procedures (e.g. specific brands of equipment). Investigators can then write and file their own IND with the FDA by modifying the CMC section to fit local conditions and adding the Investigator's proposed Clinical protocol, and NCI will provide a letter to cross-reference the NCI IND file at FDA for pharmacology, toxicology, dosimetry, and previous human experience. You may wish to consult these FMISO Frequently Asked Questions before going forward.
FMISO Transfer Agreement

Component documents for an IND for 16-α-[18F]Fluoroestradiol, [18F]FES

These documents include a full set of manufacturing and QC documents and an Investigator Drug Brochure, all of which have been accepted by the FDA as part of the NCI IND. The synthesis procedure follows that reported by Lim (Lim, JL, Zheng, L, et al: The use of 3-methoxymethyl-16 beta, 17 beta-epiestriol-O-cyclic sulfone as the precursor in the synthesis of F-18 16 alpha-fluoroestradiol. Nucl Med Biol 23:911-5, 1996). Investigators at each site can implement the synthesis and testing in their radiochemistry laboratory. There is a CMC template that will need to be modified to match the local procedures (e.g. specific brands of equipment). Investigators can then write and file their own IND with the FDA by modifying the CMC section to fit local conditions and adding the Investigator's proposed Clinical protocol, and NCI will provide a letter to cross-reference the NCI IND file at FDA for pharmacology, toxicology, dosimetry, and previous human experience. You may wish to consult these FES Frequently Asked Questions before going forward.
FES Transfer Agreement