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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. Four document sets are currently available: F-18 fluorothymidine (FLT), [18F]Fluoromisonidazole, 1H-1-(3-[18F]-Fluoro-2-Hydroxy-Propyl)-2-Nitro-Imidazole, [18F]FMISO, 16-α-[18F]Fluoroestradiol and Sodium [F-18]fluoride.

PET drug information from the U.S. Food and Drug Administration (FDA) can be found here: FDA PET Page.

New Drug Application Approved for Sodium Fluoride F18

The NCI announced (press release) on February 1, 2011 that the FDA has approved a New Drug Application (NDA) from the National Cancer Institute (NCI), part of the National Institutes of Health, for a new strength of a previously discontinued drug, Sodium Fluoride F18, for use in bone scans. Unlike Technetium-99m (Tc-99m), which was previously the only approved radioactive tracer for bone scans. Sodium Fluoride F18 is easier to produce and isn't subject to the recent nationwide risk of shortages.
See a history and rationale behind NCI's filing an NDA for Sodium Fluoride F18,
Questions/Answers Regarding the NDA Filing for Sodium Fluoride F18,
and Prescribing Information for Sodium Fluoride F18.

Component documents for an IND for [18F] sodium fluoride

This posting includes an Investigator Drug Brochure, which has been accepted by the FDA as part of the NCI IND. The sodium fluoride can be prepared on-site or purchased from any vendor which has filed a Drug Master File (DMF) for it. There is a USP monograph for Sodium Fluoride F 18 Injection which establishes appropriate quality standards. Investigators then write and file their own IND with the FDA by supplying the CMC section if locally prepared and adding the Investigator's proposed Clinical protocol. NCI will provide a letter to cross-reference the NCI IND file at FDA for pharmacology, toxicology, dosimetry, previous human experience and reference to commercial drug master files. You may wish to consult these NaF Frequently Asked Questions before going forward. The Investigator's Drug Brochure Template is given on the next page.

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.
The FLT Transfer Agreement describes conditions of use of the FLT Production Documents.  See the FLT Investigator's Brochure as a Adobe Acrobat file or a Word document.  

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. Please see documentation for FMISO 14-day toxicology and Ames test information.
The FMISO Transfer Agreement describes conditions of use of the FMISO Production Documents.

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.
The FES Transfer Agreement describes conditions of use of the FES Production Documents. See the FES Investigator's Brochure as a Adobe Acrobat file or a Word document.

For additional information, contact:

G. Craig Hill, Ph.D.
Email: hillgc@mail.nih.gov
Phone: 301-435-9184