[Federal Register Volume 65, Number 180 (Friday, September 15, 2000)]
[Notices]
[Pages 55950-55951]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-23768]


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DEPARTMENT OF ENERGY


Office of Science; Office of Science Financial Assistance Program 
Notice 00-20; Medical Applications Program

AGENCY: U.S. Department of Energy (DOE).

ACTION: Notice inviting grant applications.

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SUMMARY: The Office of Biological and Environmental Research (OBER) of 
the Office of Science (SC), U.S. Department of Energy (DOE), hereby 
announces its interest in receiving grant applications to support one 
specific research area within the Medical Applications Program: 
Innovative approaches to cell-targeted ablation therapy for cancer with 
in vivo radiation techniques. The emphasis will be on the therapeutic 
use of ionizing radiation such as may be achieved with radionuclide 
therapy or dual step techniques such as boron neutron capture therapy. 
The specific goals include development of novel ligands and delivery 
techniques to target and treat cancer at the cellular level. Special 
consideration will be given to applications reflecting a well 
integrated, multidisciplinary team effort of scientists with skills to 
address such complex challenges as chemical ligand synthesis, tumor 
targeting, and dosimetry. Access to appropriate tumor models for pre-
clinical testing will impact funding considerations. Applications for 
clinical trials using already developed compounds and techniques will 
not be considered.

DATES: Before preparing a formal application, potential applicants are 
encouraged to submit a brief pre-application. All pre-applications 
referencing Program Notice 00-20, should be received by DOE by 4:30 
p.m., E.D.T., October 16, 2000. A response encouraging or discouraging 
the submission of a formal application will be communicated by 
electronic mail within approximately 2 weeks.
    Formal applications submitted in response to this Notice must be 
received by 4:30 p.m., E.S.T., January 5, 2001, to be accepted for 
merit review and consideration of an award in Fiscal Year 2001.

ADDRESSES: Pre-applications referencing Program Notice 00-20, are to be 
sent, if possible, by E-mail or Fax to Ms. Sharon Betson 
([email protected]; Fax: 301-903-0567). Pre-applications 
will also be accepted if mailed to the following address: Ms. Sharon 
Betson, Office of Biological and Environmental Research, SC-73, 19901 
Germantown Road, Germantown, MD 20874-1290.
    Formal applications referencing Program Notice 00-20, should be 
forwarded to: U.S. Department of Energy, Office of Science, Grants and 
Contracts Division, SC-64, 19901 Germantown Road, Germantown, MD 20874-
1290, Attn: Program Notice 00-20. This address must also be used when 
submitting applications by U.S. Postal Service Express Mail or any 
other commercial overnight delivery service, or hand-carried by the 
applicant. An original and seven copies of the application must be 
submitted.

FOR FURTHER INFORMATION CONTACT: Peter T. Kirchner, MD, or Prem C. 
Srivastava, Ph.D., Office of Biological and Environmental Research, 
Medical Sciences Division (SC-73), U.S. Department of Energy, 19901 
Germantown Road, Germantown, MD 20874-1290, telephone: (301) 903-3213, 
FAX: (301) 903-0567, E-mail: [email protected] or 
[email protected]. The full text of Program Notice 00-20 
is available via the Internet using the following web site address: 
http://www.sc.doe.gov/production/grants/grants.html.

SUPPLEMENTARY INFORMATION: The Medical Applications Program supports 
directed nuclear medicine research in the areas of radiopharmaceutical 
development, molecular nuclear medicine and medical imaging to promote 
the use of radioisotopes for non-invasive diagnosis and therapy. 
Selective molecular targeting with radioligands will facilitate the 
analysis of cellular and tissue function and may enable purposeful 
disruption of specific cellular functions in tissues requiring therapy. 
The in-vivo distribution of radiopharmaceuticals and other cell-
directed ligands may be defined and monitored with a variety of in-vivo 
imaging methods, such as the use of gamma cameras, positron emission 
tomographs (PET), fluorescent techniques and a variety of optical 
techniques. The development of in-vivo imaging techniques based on 
cell-targeting should assist reliable differentiation between normal 
and abnormal tissues at the molecular and/or metabolic levels, ideally 
leading to the development of more effective therapies and useful 
monitoring techniques for such therapies. Thus, highly selective 
substrate-binding molecules, when labeled with high energy-emitting 
radioisotopes or other noxious or pre-sensitizing agents, can become 
powerful tools for targeted molecular therapy of cancer.
    Basic research in molecular biology has provided new insights to 
the molecular basis of human disease and its potential molecular 
targets. DOE's current Molecular Nuclear Medicine Program encourages 
development of new technologies for molecular delivery of radioisotopes 
to disease target sites with a high degree of molecular precision, 
recognition, and target selectivity. The availability of new technology 
for high resolution imaging of small animals should facilitate the 
evaluation of new molecular ligands for their potential value and 
subsequent use in human trials of cancer therapy.
    This Notice is to solicit grant applications for developing 
innovative approaches to cell-targeted ablation therapy for tumors with 
in vivo radiation techniques. A well integrated team effort by 
scientists from overlapping disciplines of chemistry, 
radiopharmaceutical chemistry, cellular and molecular biology, and 
biological and nuclear medicine imaging will be judged important in the 
evaluation of submitted research applications. Methodological 
approaches that can be adapted to deliver more than one type

[[Page 55951]]

of radiation or more than one radioisotope to the target sites are 
encouraged. It will be important for each application to consider also 
the following objectives:
    (1) Techniques to ensure highly selective tumor targeting by the 
proposed ligands;
    (2) Efficient screening techniques for selecting candidate ligands 
for in-vivo testing;
    (3) Preliminary data indicating reasonable likelihood of success 
for in-vivo targeting of primary tumors and their metastases in pre-
clinical animal trials;
    (4) Reliable approaches for dosimetry calculations to normal 
tissues and to tumor sites based on 3-dimensional modeling;
    (5) Measurement techniques for accurately assessing the success of 
tumor targeting in vivo;
    (6) Measurement techniques for assessing therapy effects in vivo at 
the molecular, cellular and metabolic levels.

Program Funding

    It is anticipated that up to $2 million will be available for 
multiple awards in Fiscal Year 2001 contingent upon the availability of 
appropriated funds and the scientific merit of the submitted 
applications. Previous awards have ranged from $200,000 to $400,000 per 
year (direct plus indirect costs) with terms lasting up to three years. 
Similar award sizes are anticipated for new grants. Applications may 
request project support up to three years, with out-year support 
contingent on the availability of appropriated funds, satisfactory 
progress in the research proposed, and programmatic needs.

Pre-Applications

    A brief pre-application should be submitted. The cover sheet of the 
pre-application should list the title of the project, the institution, 
and the principal investigator's name, address, telephone, fax, and E-
mail address. The pre-application should not exceed two pages (in 
addition to the cover sheet). It should identify and describe the 
research objectives, the methods proposed for accomplishment of the 
research, and the key members of the scientific team responsible for 
this effort. Pre-applications will be evaluated relative to the scope 
and objectives of this solicitation.

Merit Review

    Applications will be subjected to scientific merit review (peer 
review) and will be evaluated against the following evaluation criteria 
listed in descending order of importance as codified at 10 CFR 
605.10(d):

1. Scientific and/or Technical Merit of the Project
2. Appropriateness of the Proposed Approach and Methods
3. Competency of the Research Team and Adequacy of Available
Resources
4. Justification of the Proposed Budget

    The evaluation will include program policy factors such as the 
relevance of the proposed research to the terms of the announcement and 
the agency's programmatic needs. It should be noted that external peer 
reviewers are selected on the basis of their scientific expertise and 
the absence of conflict-of-interest issues. Non-federal reviewers may 
be used, and submission of an application constitutes agreement that 
this review process is acceptable to the investigator(s) and the 
submitting institution.

Submission Information

    Information about the development, submission of applications, 
eligibility, limitations, evaluation, the selection process, and other 
policies and procedures may be found in 10 CFR Part 605, and in the 
Application Guide for the Office of Science Financial Assistance 
Program.
    Electronic access to the Guide and required forms is made available 
via the World Wide Web at: http://www.sc.doe.gov/production/grants/grants.html. DOE is under no obligation to pay for any costs associated 
with the preparation or submission of applications if an award is not 
made. In addition, in response to this Notice, the Project Description 
must be 25 pages or less, exclusive of attachments, and the application 
must contain a table of contents, an abstract or project summary, 
letters of intent from collaborators (if any), and short curriculum 
vitae, consistent with National Institutes of Health guidelines. Block 
15 of the SC grant face page (form DOE F4650.2) should list the PI's 
phone number, fax number, and E-mail address.
    DOE policy requires that potential applicants adhere to 10 CFR 745 
``Protection of Human Subjects'' or such later revision of those 
guidelines as may be published in the Federal Register.
    The Office of Science as part of its grant regulations requires at 
10 CFR 605.11(b) that a recipient receiving a grant and performing 
research involving recombinant DNA molecules and/or organisms and 
viruses containing recombinant DNA molecules shall comply with NIH 
``Guidelines for Research Involving Recombinant DNA Molecules,'' which 
is available via the world wide web at: http://www.niehs.nih.gov/odhsb/biosafe/nih/rdna-apr98.pdf, (59 FR 34496, July 5, 1994,) or such later 
revision of those guidelines as may be published in the Federal 
Register.
    The Catalog of Federal Domestic Assistance Number for this program 
is 81.049, and the solicitation control number is ERFAP 10 CFR Part 
605.

    Issued in Washington, DC, on September 1, 2000
John Rodney Clark,
Associate Director of Science for Resource Management.
[FR Doc. 00-23768 Filed 9-14-00; 8:45 am]
BILLING CODE 6450-01-P