Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Wounds and Injuries

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Lung Injury

Lung Diseases

Respiratory Tract Diseases

Thoracic Injuries

Central Nervous System Depressants

All Drugs and Chemicals

Xenon

Anesthetics

Anesthetics, Inhalation

Anesthetics, General

The primary objective of this study is to determine an optimized set of scan parameters for HP 129Xe MR diffusion-weighted imaging, HP 129Xe MR ventilation imaging, HP 129Xe Chemical Shift Saturation Recovery (CSSR) and Xenon polarization Transfer Contrast (XTC) MRI that will produce clear, anatomically and clinically relevant images of the lungs in up to 10 healthy participants and up to 10 participants with NSCLC. The primary objective will be completed before moving onto the secondary objective.

The secondary objective of this study is to delineate functional versus non-functional lung tissue and the effects of radiotherapy. This objective will be explored by performing these five optimized techniques with up to 10 participants with NSCLC at three time points: before radiotherapy begins, at the end of radiotherapy, and at least 10-weeks post-radiation treatment. These results will be correlated with those from PFTs and CT scans performed at corresponding time points.

Participants will be asked to inhale the xenon-129 contrast agent according to procedure for gas administration. The success criterion of the drug is a obtained Xe MRI lung image with reasonable signal level. The clinical MRI scanner Philips Achieva 3.0T will be equipped with 129Xe Quadrature Transreceive Lung Coil (Large and Small) to acquire 129Xe lung images. The resonator length of the large coils is equal to 122 cm, whereas the same size of the small coil is equal to 106 cm. The success criterion of the device performance is the obtained reasonable Xe MRI lung image.

Hyperpolarized xenon-129 MRI

Mitchell Albert, PhD

Lung cancer is the leading cause of cancer death in the world; each year lung cancer claims over 20 000 lives in Canada and more than one million lives globally (1). Significant improvements have been made in treating many other types of cancer, but lung cancer care has not realized similar successes. Seventy percent of cancers are at an advanced stage at diagnosis, and radiation plays a standard role as a part of both radical and palliative therapy in these cases. Normal lung tissue is highly sensitive to radiation. This sensitivity poses a serious problem; it can cause radiation pneumonitis or fibrosis (RILI), which may result in serious disability and sometimes death. Thirty-seven percent of thoracic cancer patients treated with radiation develop RILI; in 20% of radiation therapy cases, injury to the lungs is moderate to severe (2). In addition, radiation-induced pneumonitis that produces symptoms occurs in 5-50% of individuals given radiotherapy for lung cancer (3, 4).

The chances of clinical radiation pneumonitis are directly related to the irradiated volume of lung (5). However, radiation planning currently assumes that all parts of the lung are equally functional. Identification of the areas of the lung that are more functional would be beneficial in order to prioritize those areas for sparing during radiation planning. In order to limit the amount of RILI to preserve lung function in patients, clinicians plan radiation treatment using conformal or intensity-modulated radiotherapy (IMRT). This makes use of computed tomography (CT) scans, which take into account anatomic locations of both disease and lung but cannot assess the functionality of the lung itself. An important component of the rationale of IMRT is that if doses of radiation entering functional tissue are constrained, radiation dose can be focused on tumours to spare functional tissues from injury to preserve existing lung function (6). Therefore, to optimally reduce toxicity, IMRT would depend on data of not only tumour location, but also regional lung function.

Pulmonary function tests (PFTs) can detect a decrease in pulmonary function due to the presence of tumours or RILI, but because the measurements are performed at the mouth, PFTs do not provide regional information on lung function. Positron emission tomography (PET) imaging may be used for radiation planning, but PET is limited in its ability to delineate functional tissue, it requires administration of a radiopharmaceutical agent, it is a slow modality, and, because it requires use of a cyclotron, it is expensive. Single-photon emission computed tomography (SPECT) imaging to measure pulmonary perfusion as a means for delineating functional tissue has been explored (7-11). Whereas SPECT can detect non-functional tissue, it offers spatial resolution that is only half that of CT or PET, and it does not possess the anatomical resolution necessary for optimal use with IMRT. Furthermore, like PET, SPECT is a slow modality. Given the limitations of existing imaging modalities, there is an urgent unmet medical need for an imaging modality that can provide complimentary data on regional lung function quickly and non-invasively, and that will limit tissue toxicity in radiotherapy for non-small cell lung cancer (NSCLC).

Hyperpolarized (HP) gas magnetic resonance imaging (MRI) has the potential to fill this unmet need. HP gas MRI, uses HP xenon-129 (129Xe) to provide non-invasive, high resolution imaging without the need for ionizing radiation, paramagnetic, or iodinated chemical contrast agents. HP gas MRI offers the tremendous advantages of quickly providing high-resolution information on the lungs that is noninvasive, direct, functional, and regional. Conventional MRI typically detects the hydrogen (1H) nucleus, which presents limitations for lung imaging due to lack of water molecules in the lungs. HP gas MRI detects 129Xe nuclei, which are polarized using spin-exchange optical pumping (SEOP) technique to increase their effective MR signal intensity by approximately 100,000 times. HP gas MRI has already been widely successful for pulmonary imaging, providing high-resolution imaging information on lung structure, ventilation function, and air-exchange function. The technology has proven useful for imaging asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis, and for assessing the efficacy of therapeutics for these diseases (12 -21). In this project, the investigators propose to develop an imaging technology for delineating regions of the lung in humans that are non-functional versus those that are viable; using hyperpolarized (HP) xenon-129 (129Xe) magnetic resonance imaging (MRI), will better inform beam-planning strategies, in an attempt to reduce RILI in lung cancer patients.

Hyperpolarized Noble Gas MRI Detection of Radiation-Induced Lung Injury

Performing HP 129Xe MR diffusion-weighted imaging, HP 129Xe MR ventilation imaging, HP 129Xe CSSR and XTC MRI the location of functional and non-functional lung tissue will be determined, and the radiotherapy will be planned based on the obtained tissue distributions. MRI results will be correlated with PFTs and CT scans.

Performing HP 129Xe MR diffusion-weighted imaging, HP 129Xe MR ventilation imaging, HP 129Xe CSSR and XTC MRI results will be correlated with those from PFTs and CT scans performed at corresponding time points to determine the effects of radiotherapy.

NOAMA

Thunder Bay Regional Health Research Institute

Symptoms and General Pathology

Neoplasm Metastasis

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Radiopharmaceuticals

All patients included for treatment with stereotactic radiotherapy for non-small cell lung cancer or lung metastasis will benefit from a pre-therapeutic functional assessment including:

* The standard functional assessment recommended before performing an SBRT.
* A perfusion PET/CT scan

The treatment planning will be carried out in 2 stages:

* First, an anatomical planning will be carried out, blinded to the PET results.
* Then, a functional planning, respecting the standard constraints applied during anatomical planning, but also incorporating a new "functional lung volume" constraint defined by pulmonary PET, will then be carried out.

A follow-up will be carried out for 12 months, including repeated perfusion PET/CT imaging at 3 and 12 months

The radiopharmaceutical used for lung perfusion PET consists in human albumin macroaggregates labeled with Ga-68 (68Ga-MAA). 68Ga- MAA are administrated intravenously.

Pre-therapeutic imaging test

This is a prospective study evaluating the feasibility of treatment planning integrating lung perfusion PET/CT using Ga68-MAA to preserve functional lung areas during stereotactic body radiation therapy (SBRT).

Lung perfusion PET / CT is a new imaging modality based on the use of the same cold molecules as those used for a conventional perfusion lung scan. Similartly, perfusion images are obtained after intravenous administration of human albumin macroaggregates, which are embolized in pulmonary capillaries according to pulmonary blood flow. However, these cold molecules are radiolabeled, not with Technetium99m, but with Gallium68, a ß + isotope, allowing image acquisition with PET technology. The same physiological processes are therefore observed with conventional scintigraphy PET imaging, but PET is an intrinsically superior technique for image acquisition, with greater sensitivity, better spatial and temporal resolutions and the possibility to perform respiratory-gated acquisition, allowing a better definition of the pulmonary functional volumes.

The aim is to evaluate the feasability of functional lung avoidance planification using lung perfusion PET/CT imaging during SBRT.

Patients will benefit from a pre-treatment functional assessment including PET/CT imaging.

The treatment planning will be carried out in 2 stages:

* First, an anatomical planning will be carried out, blinded to the PET results.
* Then, a functional planning, respecting the standard constraints applied during anatomical planning, but also incorporating a new "functional lung volume" constraint defined by PET/CT images, will be carried out.

A follow-up will be carried out for 12 months, including repeated perfusion PET/CT imaging at 3 and 12 months.

Lung Perfusion PET / CT Using Ga68-MAA for Preservation of Lung Function During Stereotactic Pulmonary Radiation Therapy

Lung Perfusion PET / CT Using Gallium68-MMA for Preservation of Lung Function During Stereotactic Pulmonary Radiation Therapy

All collected data that underlie results in a publication

Percentage of patients for whom it is possible to reduce the dose to the functional lung (estimated during the functional planning).

A reduction in the dose to the functional lung will be defined by:

* A decrease of at least 5% in functional lung volume included in V20Gy. or
* A decrease of at least 5% in total relative lung function included in the V20G.

Percentage of activity included in the V20Gy with the anatomical planning and the functional planning.

Percentage of functional lung volume included in the V20Gy with anatomical planning and during functional planning

Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-C30 : European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Cancer module 30) at 3 months

Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-LC13 :European Organisation for Research and Treatment of Cancer- Quality of Life Questionnaire - Lung Cancer module 13) at 3 months

Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-C30 : European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire -Cancer module 30) at 6 months

Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-LC13 : European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Lung Cancer module 13) at 6 months

Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-C30 : European Organisation for Research and Treatment of Cancer -Quality of Life Questionnaire - Cancer module 30) at 9 months

Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-LC13 : European Organisation for Research and Treatment of Cancer -Quality of Life Questionnaire - Lung Cancer module 13) at 9 months

Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-C30 : European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Cancer module 30) at 12 months

Pulmonary toxicity defined according to EORTC (European Organisation for Research and Treatment of Cancer) criteria (Common Terminology Criteria for Adverse Events 5.0, EORTC QLQ-LC13 : European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire - Lung Cancer module 13) at 12 months

Results of EuroQol (EQ-5D-5L) questionnaire

Results of Pulmonary Function testing (PFT) : FEV1

Results of Pulmonary Function testing (PFT) : FEV1/FVC

University Hospital, Brest

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Pancreatic Neoplasms

Fibrosis

Radiation Fibrosis Syndrome

Syndrome

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Radiation Injuries

Pancreatic Cancer

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

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.

[68Ga]CBP8

Michael Lanuti, MD

Shadi Esfahani, MD

Eric Abston, MD

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.

Eligible subjects planning on receiving radiation for lung cancer or pancreatic cancer will be enrolled to undergo imaging with the PET Probe \[68Ga\]CBP8.

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Hyperpolarized Noble Gas MRI Detection of Radiation-Induced Lung Injury	NCT03632369	Radiation Induc... Non Small Cell ...	Hyperpolarized ...	18 Years -	Thunder Bay Regional Health Research Institute
Hyperpolarized Noble Gas MRI Detection of Radiation-Induced Lung Injury	NCT03632369	Radiation Induc... Non Small Cell ...	Hyperpolarized ...	18 Years -	Thunder Bay Regional Health Research Institute
Lung Perfusion PET / CT Using Ga68-MAA for Preservation of Lung Function During Stereotactic Pulmonary Radiation Therapy	NCT04942275	SBRT Non-small Cell ... Lung Metastasis	Pre-therapeutic...	18 Years -	University Hospital, Brest
Lung Perfusion PET / CT Using Ga68-MAA for Preservation of Lung Function During Stereotactic Pulmonary Radiation Therapy	NCT04942275	SBRT Non-small Cell ... Lung Metastasis	Pre-therapeutic...	18 Years -	University Hospital, Brest
Lung Perfusion PET / CT Using Ga68-MAA for Preservation of Lung Function During Stereotactic Pulmonary Radiation Therapy	NCT04942275	SBRT Non-small Cell ... Lung Metastasis	Pre-therapeutic...	18 Years -	University Hospital, Brest
Evaluation of PET Probe [68Ga]CBP8 in the Detection of Radiation Induced Tissue Injury	NCT04485286	Lung Cancer Radiation Fibro... Radiation Induc... Pancreas Cancer	[68Ga]CBP8	18 Years - 80 Years	Massachusetts General Hospital
Evaluation of PET Probe [68Ga]CBP8 in the Detection of Radiation Induced Tissue Injury	NCT04485286	Lung Cancer Radiation Fibro... Radiation Induc... Pancreas Cancer	[68Ga]CBP8	18 Years - 80 Years	Massachusetts General Hospital

Spots Global Cancer Trial Database for radiation induced lung injury