[Federal Register Volume 69, Number 47 (Wednesday, March 10, 2004)]
[Notices]
[Pages 11409-11411]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-5359]


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DEPARTMENT OF ENERGY


Office of Science Financial Assistance Program Notice DE-FG01-
04ER04-17; Innovative Technologies for In Vivo Targeted 
Radiopharmaceutical Dose Delivery and Deposition

AGENCY: 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 
announce its interest in receiving grant applications to support one 
specific research area within the Medical Applications Program: 
Innovative Technologies for In Vivo Targeted Radiopharmaceutical Dose 
Delivery and Deposition. The emphasis will be on the therapeutic use of 
ionizing radiation. The specific goals include: (1) development of 
radiochemical methodologies for labeling the targeting molecules with 
and for site-specific delivery of therapeutic dose levels of 
radioactivity, and (2) development of radiobiology-based-microdosimetry 
techniques to accurately measure and predict the potential therapeutic 
use, dose and dose rate delivery of ionizing radiation. Applicants are 
encouraged to propose innovative methodologies and technologies to 
label biological ligands with therapeutic level radioactivity, ensure 
in vivo delivery of intact radioisotopically labeled molecules to 
specific tumor cell types, and develop novel microdosimetry paradigms. 
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 preapplication. All preapplications 
referencing Program Notice DE-FG01-04ER04-17, should be received by DOE 
by 4:30 p.m., eastern time, April 12, 2004. 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., eastern time, June 15, 2004, to be accepted for 
merit review and be considered for award in Fiscal Year 2004 or early 
2005.

ADDRESSES: Preapplications referencing Program Notice DE-FG01-04ER04-
17, are to be sent, if possible, by e-mail or fax to Ms. Sharon Betson 
([email protected]; fax: 301-903-0567). Preapplications 
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 DE-FG01-04ER04-17, 
must be sent electronically by an authorized institutional business 
official through DOE's Industry Interactive Procurement System (IIPS) 
at: http://e-center.doe.gov/. IIPS provides for the posting of 
solicitations and receipt of applications in a paperless environment 
via the Internet. In order to submit applications through IIPS, your 
business official will need to register at the IIPS website. IIPS 
offers the option of using multiple files, please limit submissions to 
one volume and one file if possible, with a maximum of no more than 
four PDF files. The Office of Science will include attachments as part 
of this notice that provide the appropriate forms in PDF fillable 
format that are to be submitted through IIPS. Color images should be 
submitted in IIPS as a separate file in PDF format and identified as 
such. These images should be kept to a minimum due to the limitations 
of reproducing them. They should be numbered and referred to in the 
body of the technical scientific grant application as Color image 1, 
Color image 2, etc. Questions regarding the operation of IIPS may be e-
mailed to the IIPS Help Desk at: [email protected], or you may call 
the help desk at: (800) 683-0751. Further information on the use of 
IIPS by the Office of Science is available at: http://www.sc.doe.gov/production/grants/grants.html.
    If you are unable to submit an application through IIPS, please 
contact the Grants and Contracts Division, Office of Science at: (301) 
903-5212 or (301) 903-3604, in order to gain assistance for submission 
through IIPS or to receive special approval and instructions on how to 
submit printed applications.

FOR FURTHER INFORMATION CONTACT: 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) 903-4071, fax: (301) 903-0567, e-mail: 
[email protected]. The full text of Program Notice DE-
FG01-04ER04-17 is available via the Internet using the following Web 
site address: http://www.sc.doe.gov/production/grants/grants.html.

SUPPLEMENTARY INFORMATION: The BER Medical Applications Program 
supports directed nuclear medicine technology research in the areas of 
radiopharmaceutical development, molecular nuclear medicine and 
advanced biomedical imaging to promote the use of radioisotopes for 
non-invasive diagnosis and therapy.
    The early BER programs focused on understanding the physical, 
chemical and biologic consequences of radionuclide decay in the human 
body. Those studies led to much of the basic information that is still 
used today to describe the therapeutic effects of targeted 
radionuclides. DOE continued to fund projects and develop technologies 
for therapeutic effect and use of radiation that generated much of the 
current knowledge in radioisotope chemistry, identification of 
targeting agents, methods for chemical coupling of isotopes to 
targeting agents, scanning and imaging techniques, mathematical 
modeling and internal radiation dosimetry. This research has formed the 
basis for many current cancer targeted radionuclide therapy modalities 
in various stages of development.
    Current themes have developed about radiation's main molecular 
targets, absorbed energy doses and resultant radiation damage. This has 
led to the development of defined absorbed doses (Gy, Sv) that dominate 
our predictions about tumor destruction and normal tissue damage. Most 
radiobiology has been focused on radiation damage induced by high dose 
rate gamma and neutron exposures. Targeting with electrons, alpha and 
beta emitters employed at intermediate to low dose rate intensities 
requires a much better understanding of radiation damage to cells, and 
new paradigms need to be addressed to understand how best to use 
radioisotopes for selective destruction of solid tumors as compared to 
normal tissue. The recent emphasis on targeted radiopharmaceutical 
therapy agents against many forms of cancer has brought about an 
increase in the need for reliable and clinically meaningful, patient-
specific internal dose calculations. The ability to link radiation dose 
to observed biological effect of radiation is complicated by a number 
of factors, including the heterogeneity of the activity distribution 
within normal organ tissue or within tumors, the range of the particles 
delivering the therapeutic dose, the total dose received, the dose rate 
at which the dose is delivered, (which depends on

[[Page 11410]]

the radionuclide half-life), and the radiosensitivity of the tumor 
cells.
    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 precision, recognition, 
and target selectivity. The availability of new technology for high 
resolution imaging of small animals should facilitate the evaluation of 
the biological effects of ionizing radiation.
    This notice is to solicit grant applications for developing 
innovative technologies for in vivo targeted radiopharmaceutical dose 
delivery and improved radiotoxic dose deposition in the target as 
compared to normal tissue. A well integrated team effort by scientists 
from overlapping disciplines of radiochemistry, radiopharmaceutical 
chemistry, cellular and molecular radiobiology, radiation oncology, 
targeted radiation therapy, microdosimetry and modeling will be 
important. Methodological approaches and sensitive technologies that 
can be adapted to deliver, deposit, measure and predict therapeutic 
levels of radiation dose to the target sites are sought. It will be 
important for each application to address also the following 
objectives:

    1. Radiolabeling of targeting molecules at therapeutic dose levels 
of radioactivity.
    2. Considerations of radiochemical and in vivo biological viability 
(activity, stability, target specificity, and selectivity) of the 
molecule, against sensitivity to structural perturbations in the 
molecule as a result of radiolabeling.
    3. Radiopharmaceutical delivery of intact radioisotopically labeled 
molecules to tumor cells in therapeutic dose amounts.
    4. Innovative measurement techniques for evaluating biological 
effects of therapeutic radiation at low dose rates in vivo at the 
molecular, cellular and metabolic levels.
    5. Modeling and microdosimetry methods for understanding the 
biological effects of radiation at the cellular and subcellular level 
for guiding predictions about optimum radiation dose, radiation dose 
rate, and resultant tumor destruction and normal tissue damage.
    6. Measurement techniques for accurately assessing the success of 
tumor targeting in vivo.
    7. The research plan will support BER Medical Applications long 
term performance goals in scientific advancement by providing 
innovative radiopharmaceutical methodologies or technologies for use in 
solid tumor cell destruction. Applicants should note that only a 
methodology or a technology offering promise for intended use, and not 
the experimental data resulting from the proposed research will be 
considered an accomplishment and will contribute to the measures of 
performance.

Program Funding

    It is anticipated that up to $2 million will be available for 
multiple awards starting Fiscal Year 2004 to Fiscal Year 2005, 
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. Award sizes of approximately 
$400,000-$500,000 are anticipated for new, well integrated, 
multidisciplinary research 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.

Preapplications

    A brief preapplication should be submitted. The cover sheet of the 
preapplication should list the title of the project, the institution, 
and the principal investigator's name, address, telephone, fax, and e-
mail address. The preapplication 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. Preapplications 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 part 
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.


[[Page 11411]]


    Issued in Washington, DC, March 3, 2004.
Martin Rubinstein,
Acting Director, Grants and Contracts Division, Office of Science.
[FR Doc. 04-5359 Filed 3-9-04; 8:45 am]
BILLING CODE 6450-01-P