During treatment recurrent cancers build up multidrug resistance to conventional and novel chemotherapeutic agents representing a formidable challenge in clinical cancer therapy, especially for the effective treatment of gynecological malignancies. This R01 proposal describes a targeted-, combination imaging agent and therapeutic nanoemulsion, designated NMI-500, designed to provide timely diagnostic information on where the co-deliver treatment is accumulating and provide clinicians the quantitative insight to adjust treatment schedules in light of this new information. A team of investigators from two commercial and two academic organizations will collaborate to develop this clinically translatable strategy, initially addressing recurrent multidrug resistant phenotype. NMI-500 uses folate to specifically target docetaxel (DTX), and gadolinium (Gd) an MR imaging agent to localized disease as well as distal metastases. NMI-500's targeting moiety folate is known to improve uptake by tumors expressing folate receptor alpha (FR-a). FR- a, largely absent from normal tissue, has been shown to be over expressed on >80% of recurring ovarian tumors. In breast cancer high FR-an expression has been linked to poor clinical outcomes. The imaging component of NMI-500 will be achieved with the MRI contrast agent Gd, which has been shown to enhance contrast efficiency when conjugated to a nanoemulsion.
1 Specific aims will assess and validate the imaging, targeting, efficacy and pharmacokinetics of the combination imaging/chemotherapeutic product, NMI-500.

Public Health Relevance

As stated in the PAR ".nano-carriers developed for one or more imaging systems for the purposes that include transport of therapeutic agents, adds complexity to their design, optimization and validation". Our proposal challenges the paradigm that such complexity cannot be overcome to complete the cycle of innovation by translating basic science into clinical strategies to detect in real-time the accumulation of therapy at the primary and distal metastasises. We strongly believe complex combination modalities like NMI-500 will be part of the personalized medicine revolution that is only now beginning and its first target should be the dismal mortality rates associated with ovarian cancer. During treatment recurrent cancers build up multidrug resistance to conventional and novel chemotherapeutic agents representing a formidable challenge in clinical cancer therapy, especially for the effective treatment of gynecological malignancies. This R01 proposal describes a targeted-, combination imaging agent and therapeutic nanoemulsion, designated NMI-500, designed to provide timely diagnostic information on where the co-deliver treatment is accumulating and provide clinicians the quantitative insight to adjust treatment schedules in light of this new information. A team of investigators from two academic and two commercial organizations will collaborate to develop this clinically translatable strategy, initially addressing recurrent multidrug resistant phenotype. NMI-500 uses folate to specifically target docetaxel (DTX), and gadolinium (Gd) an MR imaging agent to localized disease as well as distal metastases. NMI-500's targeting moiety folate is known to improve uptake by tumors expressing folate receptor alpha (FR-a). FR- a, largely absent from normal tissue, has been shown to be over expressed on >80% of recurring ovarian tumors. In breast cancer high FR-an expression has been linked to poor clinical outcomes. The imaging component of NMI-500 will be achieved with the MRI contrast agent Gd, which has been shown to enhance contrast efficiency when conjugated to a nanoemulsion.
1 Specific aims will assess and validate the imaging, targeting, efficacy and pharmacokinetics of the combination imaging/chemotherapeutic product, NMI-500.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA158881-02
Application #
8248798
Study Section
Special Emphasis Panel (ZRG1-SBIB-U (55))
Program Officer
Baker, Houston
Project Start
2011-04-01
Project End
2016-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
2
Fiscal Year
2012
Total Cost
$540,181
Indirect Cost
$179,936
Name
Nemucore Medical Innovations, Inc.
Department
Type
DUNS #
828287222
City
Wellesley
State
MA
Country
United States
Zip Code
02481
Shah, Nina R; Tancioni, Isabelle; Ward, Kristy K et al. (2014) Analyses of merlin/NF2 connection to FAK inhibitor responsiveness in serous ovarian cancer. Gynecol Oncol 134:104-11