SBIR-STTR Award

Worldwide, a person dies from cancer every 5 seconds. Positron emission tomography (PET) is an effective tool that is critical in diagnosing cancer and monitoring treatment efficacy. PET imaging relies on use of short-lived radioisotopes. Commercial distribution of the most commonly used radio tracer, [18F]FDG, has resulted in 80% patient population coverage in the U.S, Western Europe and Japan. However, the "emerging world" (~85% of the world's population) still does not have ready access to [18F]FDG. ABT Molecular Imaging, Inc. (ABT) is focused on increasing PET access in the U.S. and worldwide. The firm's proprietary "Dose on Demand(tm)" Biomarker Generator (BG) greatly simplifies production of [18F]FDG. It also reduces the investment required by healthcare institutions to introduce PET diagnostics into new regions. The need for PET- related advances remains, however. The [18F]FDG biomarker is not the only one required for successful diagnosis/treatment monitoring of cancers. [18F]FLT has been shown to provide complementary information [18F]FDG regarding tumor proliferation in a range of cancers constituting 72% of all existing cases (see Comm. Plan Section A), yet it costs $3000-$4000/dose where available. [18F]FLT has shown so much promise that the National Cancer Institute has an established IND (11/2004) for [18F]FLT to actively encourage investigators to cross-file on (there are more than 350 clinical trials). The Fast Track SBIR project proposed here will provide the funding needed to develop and validate ABT's ability to automatically synthesize and perform automatic QC testing on [18F]FLT simplifying site IND submissions with ABT support. The envisioned ABT system will generate [18F]FLT for ~$250/dose using disposable dose-synthesis cards that can be used in-between [18F]FDG doses. The challenges to integrating [18F]FLT are (1) producing enough F-18 to account for the synthesis yield of [18F]FLT, (2) automating synthesis, and (3) automating QC tests of [18F]FLT on the BG system. For this Fast Track, ABT's PI, Dr. Khachaturian, will lead an expert R&D team of 12 in pursuing 3 Phase I and 3 Phase II Aims: (Aim 1) Validate the feasibility of increasing the amount of [18F] produced by the cyclotron from 1 to 1.7 [mCi/min]; (Aim 2) produce one unit dose of [18F]FLT (2.0-3.6 [mL], 2.5-5 [mCi]) with both US and EU precursors; and (Aim 3) pass the US and EU pharmacopeia quality controls tests. Phase I verification will fully validate proof of concept, such that Phase II development ca focus on ensuring consistent [18F]FLT yield and quality for manufacturing. The Phase II Aims are: (Aim 4) F-18 yield shall be >1.7 [mCi/min] at 3s for n = 4 targets and 20 runs/target; (Aim 5) 24 consecutive unit doses of [18F]FLT can be synthesized with both labeling precursors; and (Aim 6) 24 consecutive unit [18F]FLT doses will pass the US and EU pharmacopeia requirements. Phase III support will come from ABT's current investors and will enable the distribution of [18F]FLT, contingent upon receiving the NIH Fast Track support and meeting the Phase I and II R&D goals.

Public Health Relevance Statement:


Public Health Relevance:
Even with the great recent advances we have made against cancer, a person still dies from the disease every 5 seconds-meaning that we still have much more yet to do in terms of diagnosing, monitoring, and treating cancer. Positron Emission Tomography (PET) is an effective tool that is critical in diagnosing cancer and monitoring treatment, and [18F]FLT is an important PET biomarker than can be used to image tumor proliferation, yet [18F]FLT availability is limited in the U.S. and worldwide by high costs ($3000-$4000/dose). This Fast Track SBIR project is focused on developing and commercializing a novel method of producing [18F]FLT that would reduce the cost to ~$250/dose via proprietary ABT technology-thereby making this enabling component of PET-based cancer monitoring much more available throughout the U.S. and internationally.

Project Terms:
Accounting; Aluminum Oxide; Anions; base; Biochemical; Biological Markers; cancer diagnosis; cancer imaging; cancer therapy; Capital; Cation Exchange Resins; Chemistry; Clinical Trials; commercialization; cost; Cyclotrons; Data; detector; Development; Diagnosis; Diagnostic; Disease; Dose; Endotoxins; Ensure; European; evaporation; Excision; FLT3 gene; Funding; Goals; Healthcare; Heating; High Pressure Liquid Chromatography; Hydrolysis; Image; in vivo; Institution; Investments; Japan; Label; Lead; Letters; Life; Malignant Neoplasms; Manuals; Marketing; Measures; meetings; Metabolic; Methods; molecular imaging; Monitor; National Cancer Institute; novel; patient population; Patients; Persons; Pharmacopoeias; Phase; Population; Positron-Emission Tomography; Production; prototype; public health relevance; Quality Control; Radiation; Radio; Radioisotopes; research and development; Research Personnel; Residual state; Risk; Running; Site; Small Business Innovation Research Grant; Solid; Solutions; Solvents; System; Technology; Testing; tool; Tracer; Treatment Efficacy; tumor; United States National Institutes of Health; uptake; Western Europe; Work

Worldwide, a person dies from cancer every 5 seconds. Positron emission tomography (PET) is an effective tool that is critical in diagnosing cancer and monitoring treatment efficacy. PET imaging relies on use of short-lived radioisotopes. Commercial distribution of the most commonly used radio tracer, [18F]FDG, has resulted in 80% patient population coverage in the U.S, Western Europe and Japan. However, the "emerging world" (~85% of the world's population) still does not have ready access to [18F]FDG. ABT Molecular Imaging, Inc. (ABT) is focused on increasing PET access in the U.S. and worldwide. The firm's proprietary "Dose on Demand(tm)" Biomarker Generator (BG) greatly simplifies production of [18F]FDG. It also reduces the investment required by healthcare institutions to introduce PET diagnostics into new regions. The need for PET- related advances remains, however. The [18F]FDG biomarker is not the only one required for successful diagnosis/treatment monitoring of cancers. [18F]FLT has been shown to provide complementary information [18F]FDG regarding tumor proliferation in a range of cancers constituting 72% of all existing cases (see Comm. Plan Section A), yet it costs $3000-$4000/dose where available. [18F]FLT has shown so much promise that the National Cancer Institute has an established IND (11/2004) for [18F]FLT to actively encourage investigators to cross-file on (there are more than 350 clinical trials). The Fast Track SBIR project proposed here will provide the funding needed to develop and validate ABT's ability to automatically synthesize and perform automatic QC testing on [18F]FLT simplifying site IND submissions with ABT support. The envisioned ABT system will generate [18F]FLT for ~$250/dose using disposable dose-synthesis cards that can be used in-between [18F]FDG doses. The challenges to integrating [18F]FLT are (1) producing enough F-18 to account for the synthesis yield of [18F]FLT, (2) automating synthesis, and (3) automating QC tests of [18F]FLT on the BG system. For this Fast Track, ABT's PI, Dr. Khachaturian, will lead an expert R&D team of 12 in pursuing 3 Phase I and 3 Phase II Aims: (Aim 1) Validate the feasibility of increasing the amount of [18F] produced by the cyclotron from 1 to 1.7 [mCi/min]; (Aim 2) produce one unit dose of [18F]FLT (2.0-3.6 [mL], 2.5-5 [mCi]) with both US and EU precursors; and (Aim 3) pass the US and EU pharmacopeia quality controls tests. Phase I verification will fully validate proof of concept, such that Phase II development ca focus on ensuring consistent [18F]FLT yield and quality for manufacturing. The Phase II Aims are: (Aim 4) F-18 yield shall be >1.7 [mCi/min] at 3s for n = 4 targets and 20 runs/target; (Aim 5) 24 consecutive unit doses of [18F]FLT can be synthesized with both labeling precursors; and (Aim 6) 24 consecutive unit [18F]FLT doses will pass the US and EU pharmacopeia requirements. Phase III support will come from ABT's current investors and will enable the distribution of [18F]FLT, contingent upon receiving the NIH Fast Track support and meeting the Phase I and II R&D goals.

Public Health Relevance Statement:


Public Health Relevance:
Even with the great recent advances we have made against cancer, a person still dies from the disease every 5 seconds-meaning that we still have much more yet to do in terms of diagnosing, monitoring, and treating cancer. Positron Emission Tomography (PET) is an effective tool that is critical in diagnosing cancer and monitoring treatment, and [18F]FLT is an important PET biomarker than can be used to image tumor proliferation, yet [18F]FLT availability is limited in the U.S. and worldwide by high costs ($3000-$4000/dose). This Fast Track SBIR project is focused on developing and commercializing a novel method of producing [18F]FLT that would reduce the cost to ~$250/dose via proprietary ABT technology-thereby making this enabling component of PET-based cancer monitoring much more available throughout the U.S. and internationally.

NIH Spending Category:
Bioengineering; Cancer; Diagnostic Radiology

Project Terms:
Accounting; Aluminum Oxide; animal imaging; Anions; base; Biochemical; Biological Markers; cancer diagnosis; cancer imaging; cancer therapy; Capital; Cation Exchange Resins; Chemistry; Clinical Trials; commercialization; cost; Cyclotrons; Data; detector; Development; Diagnosis; Diagnostic; Disease; Dose; Endotoxins; Ensure; European; evaporation; Excision; FLT3 gene; Funding; Goals; Health; Healthcare; Heating; High Pressure Liquid Chromatography; Hydrolysis; Image; in vivo; Institution; Investments; Japan; Label; Lead; Letters; Life; Malignant Neoplasms; Manuals; Marketing; Measures; meetings; Metabolic; Methods; molecular imaging; Monitor; National Cancer Institute; novel; patient population; Patients; Persons; Pharmacopoeias; Phase; Population; Positron-Emission Tomography; Production; prototype; Quality Control; Radiation; Radio; Radioisotopes; research and development; Research Personnel; Residual state; Risk; Running; Site; Small Business Innovation Research Grant; Solid; Solvents; System; Technology; Testing; tool; Tracer; Treatment Efficacy; tumor; United States National Institutes of Health; uptake; Western Europe; Work