Evaluation Of PET Probe [68Ga]CBP8 In The Detection Of Radiation Induced Tissue Injury

Study Overview

Evaluation of PET Probe [68Ga]CBP8 in the Detection of Radiation Induced Tissue Injury

The goal of this study is to investigate the efficacy of [68Ga]CBP8 to detect collagen deposition in radiation induced tissue injury.

Detailed Description: The investigators have developed [68Ga]CBP8, a gallium-68 labeled collagen binding PET imaging probe, which selectively binds collagen type I. Collagen deposition is a pivotal event in several human conditions including radiation induced lung injury and in response to radiation therapy in pancreatic cancer. The investigator's studies in murine models of lung injury including radiation induced lung injury showed that [68Ga]CBP8 binds collagen with high affinity and has excellent pharmacological and pharmacokinetic profiles with high target uptake and low retention in background tissues and organs. [68Ga]CBP8 was shown in a mouse model to be effective for detecting lung fibrosis. [68Ga]CBP8 showed high specificity for pulmonary fibrosis and high target:background ratios in diseased animals. In addition, [68Ga]CBP8 could be used to monitor response to treatment. Ex vivo analysis of lung tissue from patients with idiopathic pulmonary fibrosis (IPF) supported the animal findings. The investigators have conducted preliminary studies in humans with IPF and demonstrated a significant increase in [68Ga]CBP8 signal in subjects with IPF vs healthy controls. The investigators thus aim to evaluate [68Ga]CBP8 in human subjects with radiation induced lung injury and in patients undergoing radiation therapy for pancreatic cancer: To establish the ability of [68Ga]CBP8-PET to detect radiation-induced fibrosis in lung or pancreatic cancer patients through the course of disease development with repeated measures, and correlate signal with standard measures of radiation induced tissue injury such as HRCT or MRI.

Lung Cancer
Radiation Fibrosis
Radiation Induced Lung Injury
Pancreas Cancer

DRUG: [68Ga]CBP8

2020P001899
R44CA250771 (U.S. NIH Grant/Contract)
K08CA259626 (U.S. NIH Grant/Contract)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2020-07-21	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2023-04-30
First Submitted that Met QC Criteria 2020-07-21	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2023-05-03
First Posted (ACTUAL) 2020-07-24	Results First Posted N/A	Last Verified 2023-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Diagnostic

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Lung Cancer or Pancreatic Cancer Subjects Undergoing Radiation Therapy Lung cancer or pancreatic cancer patients will receive [68Ga]CBP8 and undergo PET imaging 1) prior to radiation therapy and 2) 3-6 months after radiation therapy	DRUG: [68Ga]CBP8 Up to 15 mCi of [68Ga]CBP8 will be administered to each subject. Each subject will undergo baseline imaging prior to radiation and again 3-6 months after radiation therapy.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Lung Cancer or Pancreatic Cancer Subjects Undergoing Radiation Therapy

Lung cancer or pancreatic cancer patients will receive [68Ga]CBP8 and undergo PET imaging 1) prior to radiation therapy and 2) 3-6 months after radiation therapy

DRUG: [68Ga]CBP8

Up to 15 mCi of [68Ga]CBP8 will be administered to each subject. Each subject will undergo baseline imaging prior to radiation and again 3-6 months after radiation therapy.

Primary Outcome Measures	Measure Description	Time Frame
Ability of [68Ga]CBP8 to detect collagen deposition in areas of radiation injury.	Probe uptake will be measured in lung cancer or pancreatic cancer patients 1) prior to radiation therapy and 2) 3-6 months after radiation therapy. We expect [68Ga]CBP8 signal to be increased in post radiation measurements over pre-radiation measurements in areas of irradiated tissue. Furthermore we expect that these areas will go on to develop radiation fibrosis.	3-6 Months

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Michael Lanuti, MD

Phone Number: 6176430193

Email: mlanuti@mgh.harvard.edu

Study Contact Backup

Name: Shadi Esfahani, MD

Phone Number:

Email: AbdarEsfahani.Shadi@mgh.harvard.edu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Eligible patients will be those harboring locally advanced clinical stage I-III NSCLC who are not eligible for surgical resection, or those with stage IIIa NSCLC who are deemed candidates for multi-modality therapy, i.e. concurrent chemotherapy and radiation followed by pulmonary resection.
Age greater than 18 years
Have the ability to give written informed consent.
No tobacco use within the prior 6 months.

Age ≥ 18 years.
Life expectancy of greater than 3 months.
Ability to understand and the willingness to sign a written informed consent document.
Histologically or cytologically confirmed diagnosis of PDAC.
Tumor should be confirmed with imaging based on the standard-of-care baseline abdominal CT performed within 1 month before study visit 1.
Core samples for initial diagnosis must be available at the Department of Pathology at Massachusetts General Hospital.
Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational imaging and standard treatment regimen are eligible for this trial.
Scheduled study visit 1 within 1 month prior to starting neoadjuvant chemoradiotherapy (CRT)
Subjects undergo neoadjuvant chemotherapy followed by radiotherapy (CRT) as part of their standard clinical care and based on institutional standards.
Scheduled surgical pancreas resection within 1 month after post-CRT study visit.
Subjects are required to undergo pre-surgical CT of abdomen within 1 month after completion of standard neoadjuvant CRT as part of routine clinical work-up.

Electrical implants such as cardiac pacemaker or perfusion pump
Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, metallic tattoos anywhere on the body, tattoos near the eye, or steel implants ferromagnetic objects such as jewelry or metal clips in clothing;
Pregnant or breastfeeding (a negative quantitative serum hCG pregnancy test is required for females having child-bearing potential before the subject can participate);
Claustrophobic reactions;
Research-related radiation exposure exceeds current Radiology Department guidelines (i.e. 50 mSv in the prior 12 months);
Unable to lie comfortably on a bed inside the MR-PET;
Body weight of > 300 lbs (weight limit of the MRI table);
Determined by the investigator(s) to be clinically unsuitable for the study (e.g. based on screening visit and/or during study procedures);
Known history of pulmonary disease (Except lung cancer or smoking related lung disease,)
Pneumonia or other acute respiratory illness within 6 weeks of study entry, pneumonia defined with elevated WBC, fever, infiltrate on CXR and need for antibiotics

History of radiotherapy to the upper abdomen in the past.
History of reaction to MRI contrast (Gadoterate meglumine)
Clinical or imaging diagnosis of acute pancreatitis within 6 weeks prior to study visit
Participants with uncontrolled intercurrent illness or if determined by the investigator(s) to be clinically unsuitable for the study (e.g. based on screening and/or during study).
Participants with psychiatric illness/social situations that would limit compliance with study requirements.
Electrical implants such as cardiac pacemaker or perfusion pump;
Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, metallic tattoos anywhere on the body, tattoos near the eye, or steel implants ferromagnetic objects such as jewelry or metal clips in clothing;
eGFR of less than 30 mL/min/1.73 m2 within the past 90 days;
Pregnant or breastfeeding (a negative quantitative serum hCG pregnancy test is required for females having child-bearing potential at each PET/MRI study visit;
Claustrophobic reactions;
Research-related radiation exposure exceeds current Radiology Department guidelines (i.e. 50 mSv in the prior 12 months);
Unable to lie comfortably on a bed inside the MR-PET;
BMI > 33 (limit of the PET-MRI table)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Michael Lanuti, MD, Massachusetts General Hospital

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Montesi SB, Izquierdo-Garcia D, Desogere P, Abston E, Liang LL, Digumarthy S, Seethamraju R, Lanuti M, Caravan P, Catana C. Type I Collagen-targeted Positron Emission Tomography Imaging in Idiopathic Pulmonary Fibrosis: First-in-Human Studies. Am J Respir Crit Care Med. 2019 Jul 15;200(2):258-261. doi: 10.1164/rccm.201903-0503LE. No abstract available.
Desogere P, Tapias LF, Rietz TA, Rotile N, Blasi F, Day H, Elliott J, Fuchs BC, Lanuti M, Caravan P. Optimization of a Collagen-Targeted PET Probe for Molecular Imaging of Pulmonary Fibrosis. J Nucl Med. 2017 Dec;58(12):1991-1996. doi: 10.2967/jnumed.117.193532. Epub 2017 Jun 13.
Desogere P, Tapias LF, Hariri LP, Rotile NJ, Rietz TA, Probst CK, Blasi F, Day H, Mino-Kenudson M, Weinreb P, Violette SM, Fuchs BC, Tager AM, Lanuti M, Caravan P. Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. Sci Transl Med. 2017 Apr 5;9(384):eaaf4696. doi: 10.1126/scitranslmed.aaf4696.
Abston E, Zhou IY, Saenger JA, Shuvaev S, Akam E, Esfahani SA, Hariri LP, Rotile NJ, Crowley E, Montesi SB, Humblet V, Arabasz G, Catana C, Fintelmann FJ, Caravan P, Lanuti M. Noninvasive Quantification of Radiation-Induced Lung Injury using a Targeted Molecular Imaging Probe. medRxiv [Preprint]. 2023 Sep 26:2023.09.25.23295897. doi: 10.1101/2023.09.25.23295897.

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