NMRC JA - UVA contract - FINAL.PDF

NMRC

JUSTIFICATION AND APPROVAL

OTHER THAN FULL AND OPEN COMPETITION

1. Identification of the agency and the contracting activity.

This justification is executed by the Naval Medical Research Center (NMRC), Silver Spring, MD, on behalf of the Navy to meet the Naval Medical Research and Development mission. The Wound Infections Department (WID), within the Infectious Diseases Directorate (IDD), is located at NMRC in Building 503. The WID lab is located in 3W20.

2. Nature and/or description of the action.

Bacterial cells have selective avidity toward D-amino acids that contribute to the peptidoglycan structure of bacterial cells and provide protection from peptidase and protease attacks. [11C] D- Alanine and [11C] D-Methionine are positron emitting amino acids developed in Dr. Neumann’s laboratory that are rapidly metabolized and accumulate in bacterial cells that enable the detection of active infection in a living system [1]. The proposed action for a contract will evaluate [11C] D-Alanine and [11C] D-Methionine as bacterial-specific imaging agents that can diagnose infection using computed tomography (CT)-positron emission tomography (PET). This work will address the following:

1) The sensitivity of [11C] D-Alanine and [11C] D-Methionine as bacterial-specific imaging agents with determination of their corresponding limit of detection (LOD) for CT-PET modalities. The D-amino acids will also be compared to [11C] para-aminobenzoic acid (PABA), an alternative imaging agent that relies on bacterial biosynthesis of folate [2].

The [11C] D-amino acids will also be compared to the commonly used oncology PET tracer 2-deoxy-2-[18F] fluoro-D-glucose (FDG).

2) The ability of [11C] D-amino acids to image a broad spectrum of bacteria (both gram-negative and gram-positive) using a diversity set of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogen isolates.

3) Assess [11C]D-amino acids as imaging agents that can monitor active infections (ie. deep-seated or foreign body infections).

The Government intends on awarding a two year contract to the proposed source. The proposed source is Dr. Kiel D. Neumann and his laboratory at the University of Virginia (UVA School of Medicine) Department of Radiology and Medical Imaging. Specifically, [11C] D-Alanine and [11C] D-Methionine will be used as bacterial-specific imaging agents to detect active infections caused by a broad spectrum of Acinetobacter baumannii, Staphylococcus aureus, and Pseudomonas aeruginosa isolates, which cause significant morbidity in injured military populations.

3. Description of Supplies or Services:

A two year contract will be awarded to University of Virginia School of Medicine, Department of Radiology and Medical Imaging of the amount of $270,773 to support Dr. Neumann's CT-PET imaging research. This contract will be funded for the first year in the amount of $136,598 and the remaining second year funds will be added when new FY20 funds are received.

4. Identification of the statutory exceptions permitting other than full and open competition.

The statutory exception permitting other than full and open competition for this acquisition is 10 U.S.C. 2304(c)(1) and FAR 13.106-1(b)(1) soliciting from a single source.

5. Demonstration that the proposed contractor’s unique qualifications or the nature of the acquisition requires use of the authority cited.

Dr. Neumann and his laboratory are leaders in the field of radiology and medical imaging, with expertise in developing specific and biologically validated imaging agents. Dr. Neumann's imaging agents rely on positron emitting organic molecules that are utilized in bacterial metabolism and can rapidly accumulate in pathogenic microbes [1-3]. Dr. Neumann recently published a Nature Scientific Reports paper entitled “Imaging Active Infection in vivo Using D- Amino Acid Derived PET Radiotracers”, demonstrating the feasibility of using [11C] D-amino acids for discriminating between active infection versus sterile inflammation (heat-killed bacteria) using both gram-negative (E. Coli) and gram-positive (S. aureus) bacteria in a mouse myositis infection model. Dr. Neumann’s novel imaging agents can improve the signal-to-noise ratio with improved sensitivity to better detect lower bacterial bioburdens than conventional [18F] FDG PET radiological imaging. Dr. Neumann's technologies have significant potential as a diagnostic tool for imaging deep-seated infections that are often challenging to detect and can be broadly applied to a majority of ESKAPE pathogens, which are responsible for 30-35% of wound infections experienced by injured military personnel [4]. Moreover, such imaging agents can accurately and quantitatively detect bacterial pathogens and be used to monitor treatment in real-time for conventional antibiotics or evaluate new therapeutics without the use of invasive tissue biopsies.

As the primary developer of novel imaging agents including [11C] D-Alanine, [11C] D-Methionine, [11C] PABA, and [2-13C] Pyruvate as well as executing proof-of-concept in vivo studies that have demonstrated the feasibility of this approach, Dr. Neumann is uniquely qualified to execute the goals of this project and no other potential contractor is suitable to meet the necessary objectives of this proposal.

6. Description of efforts made to ensure that offers are solicited from as many potential sources as practicable.

A literature search was performed on NCBI Pubmed for comparable bacterial imaging diagnostic studies and research lab capabilities. While this a growing research field, several studies relied on repurposing the oncology diagnostic agent [18F] FDG, which had poor signal-to-noise ratios that could not reliably distinguish between active infections from sterile inflammation in vivo. Alternative imaging agents such as radiolabeled antibodies, antimicrobial peptides, sugars, antibiotics, enzyme ligands and bacteriophages have also been investigated as potential targeting agents for detecting deep-seated tissue infections. These agents have not been adopted into clinical practice; however, because of their limited ability to detect active bacterial infections from sterile inflammation or distinguish from other types of infection (ie. fungal, viral), poor applicability towards a broad spectrum of gram-negative and gram-positive bacterial species and strains, limited tissue penetration of the imaging agent, rapid clearance from circulation, and short probe half-lives [5]. Dr. Neumann has developed novel positron emitting compounds such as [11C] D-Alanine, [11C] D-Methionine, [11C] PABA, and [2-13C] Pyruvate that are easy to produce, have extended half-lives, provides better signal-to-noise ratios than current clinical diagnostic agents (ie. [18F] FDG), can discriminate between sterile inflammation (heat-killed bacteria) and active infection in deep-seated tissues, are rapidly metabolized and accumulate in both gram-negative (E. coli) and gram-positive (S. aureus) bacteria [1-3]. Due to the broad spectrum of ESKAPE pathogens that Dr. Neumann’s compounds are metabolized by, no other potential contractor is suitable to complete the objectives of this project, which will involve the detection of diversity sets of Acinetobacter baumannii, Staphylococcus aureus, and Pseudomonas aeruginosa that often lead to complications and long-term morbidity of blast-injured military personnel. Additionally, this project will rely on the experience and expertise of Dr. Neumann and his laboratory for the technical execution of the proposed experiments, interpretation of results, and troubleshooting during the course of this investigation.

7. Determination by the Contracting Officer that the anticipated cost to the Government will be fair and reasonable.

The Contracting Officer shall determine the anticipated cost to the Government of the supplies/services covered by this Justification and Approval and will be fair and reasonable by conducting a price analysis before an award is made.

8. Description of the market survey conducted and the results, or a statement of the reasons a market survey was not conducted.

Market research was conducted by technical experts in the November 2019 when first developing the research idea and again in April 2020. This research consisted of reviews of potential collaborators/scientists conducting research on imaging agents that could be broadly applied to detect a diverse set of ESKAPE pathogens. During in-person discussions with Dr.

Neumann, he shared his previous work developing novel positron emitting [11C] D-amino acids that are rapidly metabolized and incorporated into the peptidoglycan structure of the bacterial cells via the penicillin-binding protein (PBP) transpeptidase system, which was tested using a mouse myositis model using both gram-negative and gram-positive bacteria. Additional literature searches were conducted on current imaging modalities that could be used to detect active infection; however, other positron emitting molecules were ruled out because they could not discriminate between sterile inflammation and active inflammation or otherwise lacked broad applicability to a diverse set of bacterial species and strains. Consequently, the technical experts concluded that Dr. Neumann’s laboratory is the most appropriate source that can meet the Government’s requirements as proposed in the research plan and within the timeframe of the period of performance (2 year contract). The results of the market research memo are attached, along with a detailed statement of work that was provided to the funding source as part of the proposal. Through Dr. Neumann’s assistant professor appointment at the University of Virginia, School of Medicine, Department of Radiology and Medical Imaging he is also afforded the necessary resources, equipment, and collaborative environment needed to successfully perform the aims of this project. An extensive listing of Dr. Neumann’s relevant resources and equipment to achieve the goals of this project is included in the submission package.

9. Other facts supporting the use of other than full and open competition.

The requirement for this research contract is based on the statement of work proposed by Dr.

Neumann’s laboratory that was developed in collaboration with investigators in the Wound Infection Department, Infectious Disease Directorate at the Naval Medical Research Center. The proposal and ideas were first discussed at the end of 2019 for a future project. A statement of work was written and a proposed budget was developed that addressed the scope of the project. The funds and contract need to be executed as soon as possible so that the work can be completed in a timely fashion. Status reports with accompanying data and then a final report will be submitted to the sponsor (ie. NMRC/IDD/WID). Preliminary data generated from this project may be used to secure additional DoD funding for future work using Dr. Neumann’s experimentally validated imaging agents and significant experimental findings will be published in a peer-reviewed journal jointly selected by Dr. Neumann and NMRC. If other suitable vendor(s) became available, a full and open competition may be considered.

10. Listing of Sources, if any, which expressed, in writing, an interest in the acquisition.

To date, no other sources have written to express an interest. Any sources expressing interest in response to the synopsis will receive consideration.

11. Statement of actions, if any, the agency may take to remove or overcome any barriers to competition before any subsequent acquisition for the supplies or services required.

For the reasons set forth in Paragraph 5, NMRC has no plans at this time to compete future contacts for the types of supplies/services covered by this document. If another potential source emerges, NMRC will assess whether competition for future requirements is feasible.

12. Point of Contact.

The point of contact at the Naval Medical Research Center, Silver Spring, MD, regarding the contents of the sole source justification is Deborah M. Sharpe, who may be reached at (301) 319- 6471.

References:

1) Neumann KD, et al. Imaging active infection in vivo using d-amino acids derived PET radiotracers. Nature Scientific Reports 2017; 7: 7903: DOI:10.1038/s41598-017-08415-x

2) Mutch C, et al. [11C] Para-Aminobenzoic Acid: A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism. American Chemical Society Infectious Diseases 2018; 4(7): 1067-1072.

3) Sriram R, et al. Detection of Bacteria-Specific Metabolism Using Hyerpolarized [2-13C] Pyruvate. American Chemical Society Infectious Diseases 2018; 4(5): 797-805.

4) Boucher HW, et al. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 2009; 48: 1-12.

5) Oosten MV, et al. Targeted imaging of bacterial infections: advances, hurdles and hopes.

Federation of European Microbiological Societies Microbiology Reviews, 2015;

fuv029(39): 892-916.

TECHNICAL AND REQUIREMENTS CERTIFICATION REQUIRED

BY NAVSUP 4200.83 series I certify that the facts and representations under my cognizance which are included in this justification and approval and which form a basis for this justification are complete and accurate.

Technical Cognizance

301-319-7428 Name: CDR Mark Simons Phone Date Title: Department Head Department/Command: Wound Infections Department, Naval Medical Research Center

Requirements Cognizance

301-319-7428 Name: CDR Mark Simons Phone Date Title: Department Head Department/Command: Wound Infections Department, Naval Medical Research Center

CONTRACTING OFFICER CERTIFICATION

I certify that this justification is accurate and complete to the best of my knowledge.

Deborah M. Sharpe Phone Date Contracting Officer

12 May 2020

12 May 2020

Technical Cognizance