INDs for PET Molecular Imaging Probes—Approach by an Academic Institution

Mosessian, Sherly; Duarte-Vogel, Sandra; Stout, David; Roos, Kenneth P.; Lawson, Gregory; Jordan, Maria C.; Ogden, Amanda; Matter, Cheryl; Sadeghi, Saman; Mills, George Q.; Schelbert, Heinrich R.; Radu, Caius G.; Czernin, Johannes; Couto, Marcelo; Phelps, Michael E.

doi:10.1007/s11307-014-0735-2

Cited by 23 publications

(24 citation statements)

References 8 publications

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“…In the US, clinical use of PET radiotracers is conducted under the umbrella of an FDA-approved New Drug Application (NDA) or, in the case of generic PET radiotracers, an Abbreviated New Drug Application (ANDA). Human research is also conducted under governance of the FDA, via three major pathways: i) the Investigational New Drug application (IND), ii) an exploratory IND (eIND), or iii) under the oversight of a Radioactive Drug Research Committee (RDRC) (Suleiman et al 2006 ; FDA Guidance for Industry and Researchers: The Radioactive Drug Research Committee: Human Research without an Investigational New Drug Application 2010 ; Carpenter Jr et al 2009 ; Mosessian et al 2014 ). The necessary path to approval is dictated by parameters outlined below, as well as the stated purpose of the research in question (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…While the IND and eIND represent the most common pathways to FDA approval for first-in-man studies, some of the requirements (e.g., costly toxicology in two species for an IND) represent significant hurdles to overcome in the application process. One notable solution, as described by Mosessian et al, is to divide labor and preparation for different components of the application between different cores and facilities at a given institution (Mosessian et al 2014 ). In contrast, conducting human PET research under RDRC oversight represents a relatively efficient and cost effective path to FDA approval.…”

Section: Introductionmentioning

confidence: 99%

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Use of 55 PET radiotracers under approval of a Radioactive Drug Research Committee (RDRC)

Jackson

Lee

Sowa

et al. 2020

EJNMMI radiopharm. chem.

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Background In the US, EU and elsewhere, basic clinical research studies with positron emission tomography (PET) radiotracers that are generally recognized as safe and effective (GRASE) can often be conducted under institutional approval. For example, in the United States, such research is conducted under the oversight of a Radioactive Drug Research Committee (RDRC) as long as certain requirements are met. Firstly, the research must be for basic science and cannot be intended for immediate therapeutic or diagnostic purposes, or to determine the safety and effectiveness of the PET radiotracer. Secondly, the PET radiotracer must be generally recognized as safe and effective. Specifically, the mass dose to be administered must not cause any clinically detectable pharmacological effect in humans, and the radiation dose to be administered must be the smallest dose practical to perform the study and not exceed regulatory dose limits within a 1-year period. In our experience, the main barrier to using a PET radiotracer under RDRC approval is accessing the required information about mass and radioactive dosing. Results The University of Michigan (UM) has a long history of using PET radiotracers in clinical research studies. Herein we provide dosing information for 55 radiotracers that will enable other PET Centers to use them under the approval of their own RDRC committees. Conclusions The data provided herein will streamline future RDRC approval, and facilitate further basic science investigation of 55 PET radiotracers that target functionally relevant biomarkers in high impact disease states.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Use of 55 PET radiotracers under approval of a Radioactive Drug Research Committee (RDRC)

Jackson

Lee

Sowa

et al. 2020

EJNMMI radiopharm. chem.

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“…While for PET agents, considered to be injected in “trace amounts”, an exploratory investigative new drug application (eIND) pathway is available in the USA which expedites early first-in-human phase 0 clinical trials with less requirements for preclinical animal testing and the opportunity to render go-no go decisions faster [42, 43], this pathway currently does not exist for other types of contrast agents such as contrast microbubbles. However, it is conceivable that regulatory agencies becoming more familiar with a certain contrast agent (e.g., a targeted microbubble with a certain chemical composition), may expedite clinical translation if only binding ligands for molecular targeting were exchanged.…”

Section: Introductionmentioning

confidence: 99%

Ultrasound molecular imaging: Moving toward clinical translation

Abou‐Elkacem

Bachawal

Willmann

2015

European Journal of Radiology

180

167

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Ultrasound is a widely available, cost-effective, real-time, non-invasive and safe imaging modality widely used in the clinic for anatomical and functional imaging. With the introduction of novel molecularly-targeted ultrasound contrast agents, another dimension of ultrasound has become a reality: diagnosing and monitoring pathological processes at the molecular level. Most commonly used ultrasound molecular imaging contrast agents are micron sized, gas-containing microbubbles functionalized to recognize and attach to molecules expressed on inflamed or angiogenic vascular endothelial cells. There are several potential clinical applications currently being explored including earlier detection, molecular profiling, and monitoring of cancer, as well as visualization of ischemic memory in transient myocardial ischemia, monitoring of disease activity in inflammatory bowel disease, and assessment of arteriosclerosis. Recently, a first clinical grade ultrasound contrast agent (BR55), targeted at a molecule expressed in neoangiogenesis (vascular endothelial growth factor receptor type 2; VEGFR2) has been introduced and safety and feasibility of VEGFR2-targeted ultrasound imaging is being explored in first inhuman clinical trials in various cancer types. This review describes the design of ultrasound molecular imaging contrast agents, imaging techniques, and potential future clinical applications of ultrasound molecular imaging.

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“…18 F]FMAC)-were translated to the clinic (12,15). These second generation dCK probes had better sensitivity than [ 18 F]FAC in humans as reflected by improved accumulation in the bone marrow, a tissue with high dCK activity.…”

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confidence: 99%

[ ¹⁸ F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity

Kim

Liu

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and positron emission tomography (PET) imaging target in cancer. PET probes for dCK have been developed and are effective in mice but have suboptimal specificity and sensitivity in humans. To identify a more suitable probe for clinical dCK PET imaging, we compared the selectivity of two candidate compounds—[18F]Clofarabine; 2-chloro-2′-deoxy-2′-[18F]fluoro-9-β-d-arabinofuranosyl-adenine ([18F]CFA) and 2′-deoxy-2′-[18F]fluoro-9-β-d-arabinofuranosyl-guanine ([18F]F-AraG)—for dCK and deoxyguanosine kinase (dGK), a dCK-related mitochondrial enzyme. We demonstrate that, in the tracer concentration range used for PET imaging, [18F]CFA is primarily a substrate for dCK, with minimal cross-reactivity. In contrast, [18F]F-AraG is a better substrate for dGK than for dCK. [18F]CFA accumulation in leukemia cells correlated with dCK expression and was abrogated by treatment with a dCK inhibitor. Although [18F]CFA uptake was reduced by deoxycytidine (dC) competition, this inhibition required high dC concentrations present in murine, but not human, plasma. Expression of cytidine deaminase, a dC-catabolizing enzyme, in leukemia cells both in cell culture and in mice reduced the competition between dC and [18F]CFA, leading to increased dCK-dependent probe accumulation. First-in-human, to our knowledge, [18F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The selectivity of [18F]CFA for dCK and its favorable biodistribution in humans justify further studies to validate [18F]CFA PET as a new cancer biomarker for treatment stratification and monitoring.

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INDs for PET Molecular Imaging Probes—Approach by an Academic Institution

Cited by 23 publications

References 8 publications

Use of 55 PET radiotracers under approval of a Radioactive Drug Research Committee (RDRC)

Use of 55 PET radiotracers under approval of a Radioactive Drug Research Committee (RDRC)

Ultrasound molecular imaging: Moving toward clinical translation

[ ¹⁸ F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity

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INDs for PET Molecular Imaging Probes—Approach by an Academic Institution

Cited by 23 publications

References 8 publications

Use of 55 PET radiotracers under approval of a Radioactive Drug Research Committee (RDRC)

Use of 55 PET radiotracers under approval of a Radioactive Drug Research Committee (RDRC)

Ultrasound molecular imaging: Moving toward clinical translation

[ 18 F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity

Contact Info

Product

Resources

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[ ¹⁸ F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity