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Imaging zinc secretion from the exocrine pancreas for the early diagnosis of pancreatic adenocarcinoma with MRI

Award Number: K22CA241387
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 06/14/2021
PERIOD OF PERFORMANCE END DATE: 08/20/2024

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Imaging zinc secretion from the exocrine pancreas for the early diagnosis of pancreatic adenocarcinoma with MRI - PROJECT SUMMARY/ABSTRACT This proposal aims to use noninvasive molecular magnetic resonance (MR) imaging of pancreatic zinc content and secretion to detect pancreatic intraepithelial neoplasia (PanIN), as early pre-malignant pancreatic ductal adenocarcinoma (PDAC) lesions. It is estimated that 55,440 people in the US will be diagnosed with pancreatic cancer and 45,750 people will succumb to the disease in 2019. Current diagnostic techniques include the use of imaging to localize a lesion and invasive biopsy sampling to stage the cancer and obtain molecular and cellular information from the tumor. Once diagnosed, there are limited treatment options since symptomatic patients will likely already have advanced stage PDAC. Therefore, there is a need to detect PDAC lesions early and in a non-invasive manner. It is known that zinc is stored in zymogen granules in acinar cells at high levels and that zinc homeostasis is uniquely dysregulated in PDAC. We have successfully demonstrated that MR imaging with gadolinium (Gd)-based zinc sensors can report on zinc release from exocrine pancreatic tissue as a response to caerulein stimulation. In this proposal we will evaluate a panel of secretagogues, which are chemical compounds known to stimulate the secretion of zinc from ductal and/or acinar cells in the exocrine pancreas, to optimize their ability to generate zinc flux detectable with our molecular MR probe. I will then use this cell-specific metabolic zinc imaging technique to noninvasively quantify the zinc homeostatic dysregulation in pancreatic cancer mouse models by MRI. Elucidating the role of zinc homeostasis in the development of pancreatic adenocarcinoma by non-invasively measuring zinc release from acinar and ductal cells as a response to their natural secretagogues will allow us to identify biomarkers that report on molecular transformations early in the disease. This in turn could then enable patients to obtain a diagnosis at an early stage and thus have access to more effective therapies and curative surgical options. The short-term goal of this project is to optimize and characterize the stimulated zinc secretion in the exocrine pancreas and its detection in vivo with molecular MRI to identify early malignant transformations in PDAC, in doing so I will obtain the training from my advisory committee, who are experts in the field of pancreatic cancer molecular pathogenesis, histopathology, surgery, and radiology. Attaining my short-term goal will enable me to obtain expertise in the following areas: 1) Clinical pathology techniques for diagnosis of pancreatic adenocarcinoma. 2) Biomarker identification and validation. 3) Metabolic implications of zinc homeostasis in PDAC pathogenesis. This project will also allow me to generate data that will enhance my probability of success in obtaining independent NIH grant support. With the skills and knowledge obtained as a result of the research and training activities from this proposal, I will be able to reach my long-term goal of becoming an independent translational investigator using MRI to infer key metabolic, biological, and physiological characteristics of cancer pathogenesis based on metal homeostasis.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$1,673 )
2025	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Research Manpower	000	3	12/13/2024	NON-COMPETING CONTINUATION	-$1,673
														Subtotal = -$1,673

Issue Date FY: 2024 ( Subtotal = $70,000 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Research Manpower	001	3	6/11/2024	SUPPLEMENT FOR EXPANSION	$70,000
2024	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Research Manpower	000	3	3/20/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $70,000

Issue Date FY: 2023 ( Subtotal = $199,756 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Research Manpower	000	3	4/28/2023	NON-COMPETING CONTINUATION	$199,756
														Subtotal = $199,756

Issue Date FY: 2022 ( Subtotal = $253,283 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Research Manpower	001	2	9/6/2022	NON-COMPETING CONTINUATION	$53,496
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Research Manpower	000	2	5/9/2022	NON-COMPETING CONTINUATION	$199,787
														Subtotal = $253,283

Issue Date FY: 2021 ( Subtotal = $199,788 )
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Research Manpower	000	1	6/14/2021	NEW	$199,788
														Subtotal = $199,788

Grand Total All Awards = $721,154

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Imaging zinc secretion from the exocrine pancreas for the early diagnosis of pancreatic adenocarcinoma with MRI

Award Number: K22CA241387

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 06/14/2021

PERIOD OF PERFORMANCE END DATE: 08/20/2024

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