Clinical trial NCT05305937: Implantation of CEST and CESL MRI Methods for Detection of Breast Tumors
Official title: Implantation of CEST and CESL MRI Methods for Detection of Breast Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Malignant Tumor of Breast
Benign Breast Lumps
High-Risk Breast Cancer
Lead sponsor: Meir Medical Center
Sponsor class: OTHER
Collaborators: name: Tel Aviv University
First posted: 2022-03-31
Enrollment: 70
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: MRI is a well-established method in breast imaging. It gives excellent morphological information but does not reflect the metabolic activity leading to high proportion of false positive results. PET-CT fulfills this gap but suffers from low resolution and the risk of radiation damage. Lately, chemical exchange saturation transfer (CEST) MRI of glucose has been proposed as a new molecular imaging approach for diagnosing tumors given its high sensitivity at the molecular level and the known enhanced glucose uptake by tumors. Several glucose analogs were examined as possible candidates for imaging of breast tumors. One of the most promising agent for CEST-MRI is glucosamine (GlcN); owing to its phosphorylated products that accumulate in breast tumors, it enables to reflect their metabolic profile. In preclinical experiments glucosamine exhibits enhanced CEST signals in 4T1 and MCF7 implanted breast cancer cells in mice. Its potential for the human clinical application is strengthened by its lack of toxicity. Here the investigators propose to test the method for human subjects on a clinical MRI setup. The goal of this study is to develop innovative molecular imaging modality based on CEST-MRI of GlcN for the detection of breast tumors. The investigators will use the newly developed CEST-MRI modality for the detection of benign and malignant breast cancer in a clinical MRI scanner.

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Detailed description: The primary aim of this study is to develop innovative molecular imaging modality based on the chemical exchange saturation transfer MRI (CEST-MRI) of glucosamine (GlcN) to visualize and measure breast tumors. GlcN has been shown to have good breast tumor targeting properties allowing its detection in laboratory animals under CEST MRI technique. The investigators will use the newly developed CEST-MRI modality for the detection of benign and malignant breast cancer in a clinical MRI scanner

STUDY AIMS

1. Investigate the possibility of obtaining a new contrast image of breast cancer tumors using glucosamine as a new contrast agent using the CEST imaging method (Chemical Exchange Saturation Transfer chemical exchange during saturation transition) and/or the CESL (Spin Lock chemical exchange method).
2. A comparison of the contrast image obtained by the novel GlcN CEST-MRI and/or CESL-MRI methods to that obtained by traditional MRI methods like T1, T2.
3. Using the GlcN- CEST-MRI / or CESL-MRI approaches, compare the signal obtained by malignant and benign tumors, examination if these methods can distinguish between the two types of tumors.

Patients bearing solid breast tumors will be scanned at the clinical MRI setup. The scans will include short anatomical scans (of T1 and T2 images) and CEST imaging. Patients will be required to fast for at least 4 hours before the scan (can drink water during fasting). The participants will be asked to drink glucosamine solution (184 mg/kg). Patients will be scanned twice during the same MRI session, before and 2 hours after taking glucosamine orally. In addition to the CEST scans with GlcN, patients will undergo MRI scans with the standard contrast agent of gadolinium. This procedure will be done following the CEST scan. The CEST scan takes a few minutes (up to 10 minutes).

Eligibility criteria: Inclusion Criteria:

1. Women with suspicious finding/process in the breast that requires MRI examination
2. Age: Over 18 years.
3. For 10 patients of control group - patients without breast tumor, carriers of mutations in P53, BRCA2, BRCA1 or PTEN genes or women after genetic counseling who have been defined as having a 20% risk of developing breast cancer and are undergoing routine MRI.

Exclusion Criteria:

1. Pregnancy or breastfeeding
2. Sensitivity to glucosamine and / or gadolinium.
3. Renal failure with creatinine clearance less than 30 cc per minute.
4. Weight over 130 kg.
5. Patients who have undergone breast surgery in the past year.
6. Claustrophobia.
7. Cardiovascular instability, symptomatic heart disease, pacemaker, artificial heart valve.
8. Intra-body injection device.
9. A generalized (idiopathic) epileptic seizure that is pharmacologically unbalanced.
10. Metabolic instability (water economy, electrolytes, sugar).
11. Suffers from a gastrointestinal disorder that affects absorption.
12. Fever or evidence of a microbiological contaminant.
13. Women using drugs that are related to derivatives of warfarin-coumadin.
14. Women with phenylketonuria
15. Inability to sign informed consent.
16. COVID-19

In addition, all examinees will be subject to the accepted criteria for inclusion and exclusion of the MRI unit at Meir Medical Center.

Primary outcomes:
measure: Detection and diagnosis of malignant tumors in the breast
timeFrame: up to three years (MRI scans and data collection and interpretation will last up to 2 years; post processing, reports and publications will last about one more year)
Secondary outcomes:
measure: Tumor classification: benign or malignant
timeFrame: 3 years (data collection and post processing)
measure: Glucosamine CEST scale bar
timeFrame: Three years (data collection and post processing)
measure: Finding correlation between research results and selected pathological parameters to better identify breast cancer
timeFrame: 3 years (data collection and statistical evaluation)
measure: Using Mathematical model
timeFrame: up to 3 years (post processing-1 year)
Other outcomes:
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