Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R01 Clinical Trial Optional) is sponsored by National Institute of Mental Health (NIMH) and National Institute on Aging (NIA). Encourages the development and application of PET and SPECT imaging ligands as biomarkers to aid in drug discovery and the study of central nervous system disorders.

Expired PA-06-462: Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R33) This notice has expired. Check the NIH Guide for active opportunities and notices. Part I Overview Information Department of Health and Human Services Participating Organizations National Institutes of Health (NIH), ( http://www.

nih. gov ) Components of Participating Organizations National Institute of Mental Health (NIMH), ( http://www. nimh.

nih. gov ) National Institute of Neurological Disorders and Stroke (NINDS), ( http://www. ninds.

nih. gov/ ) National Institute on Aging (NIA), ( http://www. nia.

nih. gov ) National Institute of Alcohol Abuse and Alcoholism (NIAAA), ( http://www. niaaa.

nih. gov/ ) National Institute on Drug Abuse (NIDA), ( http://www. nida.

nih.

gov/ ) and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R33) This is a reissue and modification of PA-03-112 , which was previously released April 21, 2003, and now is divided into separate Funding Opportunity Announcements (FOAs) for R21/R33, R21, and R33 funding Update: The following update relating to this announcement has been issued: September 17, 2007 - Expiration Date adjusted to accommodate recent changes to standing submission deadlines, per NOT-OD-07-093.

NOTICE: Applications submitted in response to this FOA for Federal assistance must be submitted electronically through Grants. gov ( http://www. grants.

gov ) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT. This FOA must be read in conjunction with the application guidelines included with this announcement in Grants. gov/ApplyforGrants (hereafter called Grants.

gov/Apply). A registration process is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV .

Program Announcement (PA) Number: Catalog of Federal Domestic Assistance 93. 242, 93. 866, 93.

273, 93. 286, 93. 287, 93.

279, 93. 853 Release/Posted Date: August 7,, 2006 Opening Date: September 1, 2006 (Earliest date an application may be submitted Letters of Intent Receipt Date(s): Not NOTE: On time submission requires that applications be successfully submitted to Grants. gov no later than 5:00 p.

m. local time (of the applicant institution/organization). Application Submission/Receipt Date(s): Standard dates apply, please see http://grants1.

nih. gov/grants/funding/submissionschedule. htm Peer Review Date(s) : Standard dates apply, please see http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward Council Review Date(s): Standard dates apply, please see http://grants1.

nih. gov/grants/funding/submissionschedule. htm#reviewandaward Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1.

nih. gov/grants/funding/submissionschedule.

htm#reviewandaward Additional Information To Be Available Date (URL Activation Expiration Date: July 2, 2009 (now September 8, 2009 per NOT-OD-07-093 ) Additional Overview Content This Funding Opportunity Announcement (FOA) issued by the National Institute of Mental Health (NIMH), the National Institute on Aging (NIA), National Institute of Alcohol Abuse and Alcoholism (NIAAA), and the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH), invites Phase II Developmental (R33) grant applications from organizations/institutions that propose the development of novel radioligands for positron emission tomography (PET) or single photon emission computed tomography (SPECT) imaging in human brain, and that incorporate pilot or clinical feasibility evaluation in pre-clinical studies, model development, or clinical studies.

This FOA will use the NIH Exploratory/Developmental Grant Phase II (R33) award mechanism. T he proposed Phase II study should be designed to test whether application of PET and SPECT ligands will be useful as tools for pathophysiological studies of brain disorders or as biomarkers in pilot studies to quantify disease progression, adverse drug events, or treatment efficacy for brain disorders.

This funding opportunity runs in parallel with two FOAs of identical scientific scope, PA-06-461 that solicit applications using the NIH Exploratory/Developmental Grant (R21) and the NIH Exploratory/Developmental Grant and Exploratory/Developmental Grant Phase II Phased Innovation Grant (R21/R33) award mechanisms, respectively.

In addition, this funding opportunity runs in parallel with two FOAs of similar scientific intent, PA-06-017 that seek applications using the Small Business Innovation Resea rch (SBIR [ R43/R44]) grant mechanisms and the Small Business Technology Transfer ( STTR [ R41/R42]) grant mechanisms, Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each Phase II (R33) award will also vary.

The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the applications received. Budget and Project Period : The total project period for an R33 application submitted in response to this FOA may not exceed 3 years.

Direct costs are limited to less than Eligible Organizations: For profit organizations; non-profit organizations; public or private institutions, such as universities, colleges, hospitals and laboratories; units of State and local governments; eligible agencies of the Federal government; domestic or foreign institutions/organizations; faith-based or community-based organizations; Indian/Native American Tribal Government (Federally Recognized); Indian/Native American Tribal Government (Other than Federally Recognized); and Indian/Native American Tribally Designated Organization.

Eligible Project Directors/Principal Investigators (PDs/PIs): Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

Applicant organizations may submit more than one application, provided each application is scientifically distinct. application materials. The SF424 (R&R) Application Guide for this FOA is located at these Web sites: http://grants.

nih. gov/grants/funding/424/SF424_RR_Guide_General_Ver2. doc (MS Word) http://grants.

nih. gov/grants/funding/424/SF424_RR_Guide_General_Ver2. pdf For general information on SF424 (R&R) Application and Electronic Submission, see these Web sites: SF424 (R&R) Application and Electronic Submission Information: http://grants.

nih. gov/grants/funding/424/index. htm General information on Electronic Submission of Grant Applications: http://era.

nih. gov/ElectronicReceipt/ Telecommunications for the hearing impaired is available Part I Overview Information Part II Full Text of Announcement Section I. Funding Opportunity Section II.

Award Information 2. Cost Sharing or Matching 3. Other - Special Eligibility Criteria Section IV.

Application and 1. Request Application Information 2. Content and Form of Application Submission 3.

Submission Dates and Times A. Submission, Review, and Anticipated B. Submitting an Application Electronically to the NIH C.

Application Processing 4. Intergovernmental Review 6. Other Submission Requirements Section V.

Application Review 2. Review and Selection Process A. Additional Review Criteria B.

Additional Review Considerations D. Sharing Research Resources 3. Anticipated Announcement and Award Dates Section VI.

Award Administration 2. Administrative and National Policy Requirements Section VII. Agency Contact(s) 1.

Scientific/Research Contact(s) 2. Peer Review Contact(s) 3. Financial/Grants Management Contact(s) Section VIII.

Other Information - Required Federal Citations Part II - Full Text of Announcement Section I.

Funding Opportunity Description The purpose of this Funding Opportunity Announcement (FOA) issued by the National Institute of Mental Health (NIMH), the National Institute on Aging (NIA), National Institute of Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH) is to facilitate the development of agonist and antagonist PET and SPECT probes for molecular targets that are implicated in the pathophysiology of brain and behavioral disorders (e.g., receptors, intracellular messengers, disease-related proteins).

The use of radiotracers for imaging molecular events in preclinical and clinical studies is essential for understanding the circuitry that underlies normal brain function and the pathophysiology of brain disorders.

The long-term goal of this FOA is to facilitate the broad application of neuroimaging probes in pathophysiological studies, drug discovery/development research, and in biomarker development//qualification studies as quantifiable indicators of disease progression and treatment efficacy.

Tremendous opportunities exist for the application of PET and SPECT imaging in studies of the pathophysiology and treatment of brain disorders, but relatively few radioligands are currently available for functional imaging of target molecules implicated in normal brain function, aging, and in brain and behavioral disorders.

Increasing the availability of PET and SPECT radiotracers will aid in: a) understanding the abnormal biological processes which underlie mood disorders and other brain disorders; b) determining the interaction of a drug or drug candidate with a specified target; c) guiding initial dosing of new therapeutic agents; and d) as central biomarkers of the illness, with the potential to predict symptom onset, monitor the progression of the disease, for Mood Disorders Research is available at http://www.

nimh. nih. gov/strategic/stplan_mooddisorders.

cfm . This FOA is intended to stimulate the development of radioligands for molecular targets (e.g., receptors, cell adhesion molecules, intracellular messengers, and disease related proteins) that are of broad interest to the scientific community.

The widespread availability and use of these radioligands are expected to: 1) accelerate research on identifying and characterizing the neural circuits and pathways implicated in the pathophysiology of brain disorders (especially mental and behavioral disorders, substance abuse, neurodegenerative disorders, and pediatric brain disorders) and brain changes with age, and 2) facilitate the identification of new therapeutic targets and the development of new compounds as potential therapeutic agents.

Research partnerships among investigators in both academia and pharmaceutical and biotechnology industries are encouraged to more rapidly develop PET and SPECT radiotracers and apply neuroimaging in drug discovery, biomarker development//qualification, and pathophysiological studies. Molecular targets for which radioligands (agonist and antagonist ) are needed include, but are not limited to, the following.

Please contact program staff listed in Section VII. 1 . , Scientific/Research to determine program priorities and molecular targets of interest to specific NIH Institutes or refer to the internet addresses listed above for each of the participating NIH Institutes .

Receptors: adenosine; adrenergic: alpha 1, alpha 2; cannabinoid: CB1, CB2; corticotropin releasing hormone: CRF R1, CRF R2; dopamine: D1, D3, D4, D5; estrogen; GABA A subunits; GABA ion channel; GABA B; glutamatergic, glycine site; metabotropic glutamate subtypes; muscarinic subunits; neurokinin receptors: NK1, NK2, NK3; neuronal nicotinic receptor subunits: alpha 7 & alpha 4 beta 2; NMDA subunits; opioid receptors: mu, delta, kappa; serotonin: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2C, 5-HT5, 5-HT6, 5-HT7; voltage gated ion channels: Ca, Na, K M current proteins.

Transporters: vesicular ACh; GABA; glutamate; glycine; glutamine; NET; VMAT, excitatory amino acid transporters. Markers for glia, glial activation, and glial cell death. Enzymes: choline acetyltransferase; dopamine beta-hydroxylase; GABA transaminase; glutamic acid decarboxylase; glutaminergic; phosphodiesterases; tyrosine hydroxylase.

Intracellular targets: abnormal proteins or protein aggregates including synuclein, prion protein, amyloid or tau deposition; diacylglycerol; gene expression/transcription markers; markers of neurogenesis or neuronal cell death; markers of mitochondrial function; lipid metabolism; neuroinflammatory markers: cytokines, COX inhibitors; peptidases; phosphatases; phospholipases; protein kinases; stem cells.

The following objectives would make appropriate topics for proposed R33 projects. This list is not meant to be all-inclusive. In vivo imaging including micro PET (rodent and/or primate); and studies of pharmacological specificity, biodistribution, and pharmacokinetics.

Determination of toxicology/pathology (FDA approved) for submission of a Radioactive Drug Research Committee (RDRC), exploratory Investigational New Drug (IND) application or IND application based on feedback from an FDA pre-IND Exploratory IND or IND application development and submission to the FDA prior to pilot human studies.

Pilot human imaging studies with normal controls, pharmacological challenges with analyses of radiometabolites under the auspices of IRB approval (i.e., RDRC, exploratory IND or IND development and submission).

Pilot studies of the PET or SPECT radiotracer in patient/disease populations to assess its utility for research in pathophysiology, drug discovery, or Use of the NIH R33 (Phase II Developmental) Grant Mechanism This FOA utilizes the separate R33 (Phase II DevelopmentaI) grant mechanism and applications for support must provide sufficient evidence of the proof-of-principle and feasibility of the proposed in vivo PET or SPECT imaging ligands for further preclinical development or for clinical Information - Required Federal Citations , for policies related to Section II.

Award Information This funding opportunity will use the NIH Exploratory/Developmental Grant Phase II (R33) award mechanism. Applicants are encouraged to contact NIH program staff with any questions about the appropriate mechanism. See Section VII.

1 . , Scientific/Research As an applicant, you will be solely responsible for planning, directing, and executing the proposed project. This funding opportunity uses just-in-time concepts.

Applicants must complete and submit detailed budget requests using the SF424 Research and Related (R&R) Budget component provided in the SF424 (R&R) Application Package and the SF424 (R&R) Application Guide (see specifically Section 4. 7, R&R Budget Component, of the Application Guide). Modular budgets are not permitted for this funding opportunity.

Exploratory/developmental grant support is for new projects only; competing renewal (formerly competing continuation ) applications will not be accepted. Up to two resubmissions (formerly revisions/amendments") of a previously reviewed exploratory/developmental grant application may be submitted.

See Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the Institutes and Centers (ICs) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

The total project period for an R33 application submitted in response to this funding opportunity may not exceed three years. Direct costs must be limited to less than $500,000 per year. Facilities and Administrative (F&A) costs requested by consortium participants are not included in the direct cost limitation.

The award of R33 funds will be based on scientific merit (as determined by NIH staff in the context of peer review recommendations), feasibility of the proposed studies, program priorities, and availability Section III. Eligibility Information 1. A.

Eligible Institutions You may submit an application(s) if your organization has any of the following characteristics: Public or private institutions, such as universities, colleges, hospitals, and laboratories Units of State government Units of Local government Eligible agencies of the Federal government Domestic institutions/organizations Foreign institutions/organizations Faith-based or community-based organizations Indian/Native American Tribal Government (Federally Indian/Native American Tribal Government (Other than Indian/Native American Tribally Designated Organizations 1.

B. Eligible Individuals Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with his/her institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

The development and strengthening of partnerships between scientists from academia and the pharmaceutical industry is a highly desirable outcome of this FOA and is strongly encouraged. Pharmaceutical scientists are encouraged to actively participate as Project Director/Principal Investigator (PD/PI) or key personnel/collaborator in the project.

Scientists from NIH Intramural laboratories may participate as key personnel/collaborators in the project. However, intramural scientists may not serve as principle investigators while being paid with intramural funds. As key personnel/collaborators, it may become necessary to convert the grant application to a cooperative agreement grant mechanism with corresponding Terms and Conditions related to such a cooperative agreement.

However, an Intramural scientist may not receive salary, equipment, supplies, or other remuneration from this FOA. A formal letter from the intramural scientist must be included as part of the grant application with a copy of this letter sent to the Scientific Director. The letter should be limited to a description of the intramural scientist's collaborative work under the grant.

The grant applicant is responsible for writing the section of the grant that describes the proposed collaboration within the grant, which the NIH investigator should see and approve. For applications that include NIH intramural components, the intramural resource level will not be included in the total cost of the overall application. The involvement of Intramural scientists needs to be consistent with NIH Policy ( http://www1.

od. nih. gov/oir/sourcebook/ethic-conduct/ethical-conduct-toc.

htm ). 2. Cost Sharing or Matching This program encourages, but does not require, cost sharing with biotechnology, pharmaceutical, or disease foundations, as defined the current NIH Grants Policy Statement .

3. Other-Special Eligibility Criteria Applicant organizations may submit more than one application, provided each application is scientifically distinct. Section IV.

Application and Submission To download an SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www. grants. gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both: Grants. gov ( http://www. grants.

gov/GetStarted ) eRA Commons ( http://era. nih. gov/ElectronicReceipt/preparing.

htm ) PDs/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons . Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows: 1) Organizational/Institutional Registration in Grants.

gov/Get Your organization will need to obtain a Data Universal Number System (DUNS) number and register with the Central Contractor Registration (CCR) as part of the Grants. gov If your organization does not have a Taxpayer Identification Number (TIN) or Employer Identification Number (EIN), allow for extra time. A valid TIN or EIN is necessary for CCR registration.

The CCR also validates the EIN against Internal Revenue Service records, a step that will take an additional one to two business Direct questions regarding Grants. gov registration to: Grants. gov Customer Support Business Hours: M-F 7:00 a.

m. - 9:00 p. m.

Eastern Time 2) Organizational/Institutional Registration in the eRA Commons To find out if an organization is already Commons-registered, see the " List of Grantee Organizations Registered in NIH eRA Commons. Direct questions regarding the Commons registration Phone: 301-402-7469 or 866-504-9552 (Toll Free) Business hours M-F 7:00 a. m.

8:00 p. m. Eastern Time 3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) The individual designated as the PD/PI on the application must also be registered in the NIH eRA Commons.

It is not necessary for PDs/PIs to register with Grants. gov. The PD/PI must hold a PD/PI account in the Commons and must be affiliated with the applicant organization. This account cannot have any other role attached to it other than the PD/PI.

This registration/affiliation must be done by the Authorized Organization Representative/Signing Official (AOR/SO) or their designee who is already registered in the Commons. Both the PD/PI and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization.

Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their institution is already registered in both Grants. gov and the Commons .

The NIH will accept electronic applications only from organizations that have completed all necessary registrations. 1. Request Application Information Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.

gov/Apply . Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one For further assistance contact GrantsInfo, Telephone 301-710-0267, Email: [email protected] .

Telecommunications for the hearing impaired: TTY 301-451-5936. 2. Content and Form of Application Submission Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide ( MS The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH.

There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH ( e.g., the Credential log-in field of the Research & Related Senior/Key Person Profile component must contain the PD/PI’s assigned eRA Commons User ID ). Agency-specific instructions for such fields are clearly identified in the Application Guide.

For additional information, see Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications . The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional.

The forms package associated with this FOA in Grants. gov/APPLY will include all applicable components, required and optional.

A completed application in response to this FOA will include the following components: SF424 (R&R) (Cover component) Research & Related Project/Performance Site Locations Research & Related Other Project Information Research & Related Senior/Key Person Research & Related Budget PHS398 Cover Page Supplement Research & Related Subaward Budget Attachment(s) Several special provisions apply to applications submitted by foreign organizations: Charge back of customs and import fees is not allowed.

Format: Every effort should be made to comply with the format specifications, which are based upon a standard U.S. paper size of 8. 5 x 11 within each Funds for up to 8% administrative costs (excluding equipment) may be requested. Organizations must comply with Federal/NIH policies on human subjects, animals, Organizations must comply with Federal/NIH biosafety and biosecurity regulations.

See Section VI. 2 . , Administrative and National Policy Requirements.

Additional information regarding foreign grants is available in the NIH Grants Policy Statement . Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources. 3.

Submission Dates and Times Review and Anticipated Start Dates Opening Date: September 1, 2006 (Earliest date an application may be submitted Letters of Intent Receipt Date(s): Not Applicable Application Submission/Receipt Date(s): Standard dates apply, please see http://grants1. nih. gov/grants/funding/submissionschedule.

htm Peer Review Date(s) : Standard dates apply, please see http://grants1. nih. gov/grants/funding/submissionschedule.

htm#reviewandaward Council Review Date(s): Standard dates apply, please see http://grants1. nih. gov/grants/funding/submissionschedule.

htm#reviewandaward Earliest Anticipated Start Date(s): Standard dates apply, please see http://grants1. nih. gov/grants/funding/submissionschedule.

htm#reviewandaward A letter of intent is not required for this funding 3. B. Submitting an Application Electronically To submit an application in response to this FOA, applicants should access this FOA via http://www.

grants. gov/Apply and follow steps 1-4. Note: Applications must only be submitted electronically.

PAPER APPLICATIONS WILL NOT BE ACCEPTED. 3. C.

Application Processing Applications may be submitted on or after the opening date and must be successfully received by Grants. gov no later than 5:00 p. m.

local time (of the applicant institution/organization) on the application submission/receipt date(s). (See Section IV. 3.

A. for all dates.) If an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants. gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image. If everything is acceptable, no further action is necessary.

The application will automatically move forward for processing by the Division of Receipt and Referral, Center for Scientific Review, NIH, after two business days. Prior to the submission deadline, the AOR/SO can Reject the assembled application and submit a changed/corrected application within the two day viewing window. This option should be used if the AOR/SO determines that warnings should be addressed.

Reminder: warnings do not stop further application processing. If an application submission results in warnings (but no errors) it will automatically move forward after two business days if no action is taken. Please remember that some warnings may not be applicable or may need to be addressed after application submission.

If the two day window falls after the submission deadline, the AOR/SO will have the option to Reject the application if, due to an eRA Commons or Grants. gov system issue, the application does not correctly reflect the submitted application package (e.g., some part of the application was lost or didn t transfer correctly during the submission process).

The AOR/SO should first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course of action. NIH will not penalize the applicant for an eRA Commons or Grants. gov system issue.

to Reject the image after the submission deadline for a reason other than an eRA Commons or Grants. gov system failure, a changed/corrected application still can be submitted but it will be subject to the NIH late policy guidelines and may not be accepted. The reason for this delay should be explained in the cover letter attachment.

Both the AOR/SO and PD/PI will receive e-mail notifications when the application is rejected or the application automatically moves forward in the process after two days. Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants. gov and the Commons . Information related to the assignment of an application to a Scientific Review Group is also in the Commons.

The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed.

This does not preclude the submission of an application already reviewed with substantial changes, but such application must include an Introduction (maximum three pages) addressing the previous critique. Note such an application is considered a "resubmission" for the 4.

Intergovernmental Review This initiative is not subject to intergovernmental All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Pre-Award Costs are allowable.

A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: are necessary to conduct the project and would be allowable under the grant, if awarded, without NIH prior approval.

If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred.

NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See the NIH Grants Policy Statement . 6.

Other Submission Requirements The NIH requires the PD/PI to fill in his/her Commons User ID in the PROFILE Project Director/Principal Investigator section, Credential log-in field of the Research & Related Senior/Key Person Profile component. The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.

gov. For additional information, see Frequently Asked Questions Application Guide, Electronic Submission Renewal (formerly competing continuation or Type 2 ) applications are All application instructions outlined in the SF424 (R&R) Application Guide ( MS are to be followed, with the following requirements for R33 applications: R33 applications will use "Just-in-Time" concepts.

The detailed Research & Related Budget component must be used for all years. D irect costs are limited to less than $500,000 per year and the project period cannot exceed three years. Items 2-5 of the Research Plan of the R33 application may not exceed 25 pages, including tables, graphs, figures, diagrams, Introduction (required for a resubmission application): The introduction is limited to 3 pages.

Background and Significance: The applicant should identify concisely the fundamental research and/or technology or tool to be developed, its innovative nature, its relationship to presently available capabilities, and its expected impact on biomedical research.

Specific Aims: Because the goal of the R33 is to evaluate and/or validate the utility of novel radioligands for PET and SPECT imaging in preclinical or clinical studies or innovative technologies for radioligand development, hypothesis testing, per se, may not be the driving force in developing such a proposal, and therefore, may not be Preliminary Data: The project must be based on a strong rationale, and the applicant should provide evidence that the initial clinical evaluation of the proposed radiotracer is promising.

The R33 application must contain a clear description of how the project is ready to progress to an expanded development stage. The applicant should clearly state how feasibility for the project has already been demonstrated. This demonstration should include significant data.

Applications may contain results obtained during a previous R21 or equivalent grant award to support a proposal in response Annual Meeting: An annual meeting of all investigators funded through this program will be held to share progress and research insights that may further progress in the program.

For this purpose, applicants should request travel funds for the PD/PI and one additional senior investigator to attend a one-day meeting each year, the location of which will be announced. Applicants should also include a statement in their applications indicating their willingness to participate in such meetings and to cooperate with other researchers.

Plan for Sharing Research Data It is the NIH policy that the research resources developed through this FOA become readily available to the research community for further research, development, and application, in the expectation that this will lead to knowledge of benefit to the public. Applications must include a plan to share data that may be gathered in the course of the project with the scientific community.

It is expected that the principal investigator's data sharing plan will include the following elements: (1) mechanisms by which all protocols, procedures, methodologies, toxicology information, unlabeled PET or SPECT precursors, IND filing info are widely distributed to qualified investigators in the scientific community; (2) a protocol and criteria for wide dissemination of these data, information, and materials and (3) a timetable for distribution.

Applicants are invited to utilize NIH supported repositories such as the NIMH Chemical Synthesis and Drug Supply Program ( http://nimh-repository. rti. org /) or the NIDA Drug Supply Program to make unlabeled PET and SPECT ligands widely available to the scientific community.

Applicants are invited to utilize NIH supported databases such as the NIMH/Society for Non-Invasive Imaging in Drug Development (SNIDD)