PET/MR Pre- and Post Radiotherapy for Cardiopulmonary Dysfunction Evaluation

Exploratory Evaluation of Simultaneous Cardiac PET/MR, Metabolomic Markers and Circulating DNA as Possible Prognostic Markers in Identifying Patients Developing Transient or Permanent Cardiopulmonary Dysfunctions After Radiotherapy

Radiotherapy (RT) is a well-known and established therapy or adjuvant therapy for the treatment of thoracic cancer It uses a high energy radiation from x-rays, gamma rays and other charged particles that assist in damaging the cancer DNA. PET/MR as imaging biomarkers for cardiopulmonary dysfunction with a focus on Pulmonary hypertension (PH). Despite the measures taken to reduce the total radiation dose and to limit the radiation to normal tissues, there is evidence of transient or permanent radiotherapy induced myocardial and pulmonary dysfunction leading to PH in patients who receive radiotherapy above a certain threshold of received dose. To be able to Demonstrate correlation of combined PET/MR and plasma metabolomics markers in patients at risk of developing cardiopulmonary disfunction after RT.

RT is a well-known and established therapy or adjuvant therapy for the treatment of thoracic malignancies (breast cancer, lung cancer, lymphoma and others). It usually uses high energy radiation from x-rays, gamma rays or other charged particles to induce DNA damage in malignant cells. Despite the measures taken to reduce the total radiation dose and to limit the radiation to normal tissues, the signs and symptoms of radiation induced cardiopulmonary dysfunction (RICPD) still persist. However, in the majority of cases, it remains unclear which cardiopulmonary damage is the main /leading cause for the clinical symptoms the patients are experiencing. Hybrid PET/MRI is a promising technique that allows for truly simultaneous molecular, anatomic and functional imaging of the cardiopulmonary system. The simultaneity is an important aspect in this proposed study since only parameters measured at the same time in PET and MR can be used for an integrated, multimodality parameter for possible detection and prognostication of the different underlying processes of cardiopulmonary dysfunction after RT. Furthermore, certain PET-uptake of the RV have to be corrected for RV mass which is only possible with concomitant anatomical imaging. MR imaging and PET at different time point are not accurately reflective of the underlying pathophysiological pathways and metabolic state at the specific time points pre- and post radiotherapy. To our knowledge, there are no online publications of its use in the diagnosis and prognostication of cardiopulmonary dysfunction after RT and specifically PH.

Biopsy or otherwise clinically proven thoracic malignant mass which is intended to be treated with radio(chemo)therapy

(18F) Fluorodeoxyglucose (FDG) will be administered by intravenous injection at a dose of 4-5 MBq/kg.

Percentage of the perfused/ventilated lung segments will be evaluated and compared pre and post therapy by SPECT scans

Inclusion Criteria: Age ≥18 years Biopsy or otherwise clinically proven thoracic malignant mass which is intended to be treated with radio(chemo)therapy Intention to treat with radio(chemo)therapy with incidental cardiac irradiation of at least 25Gy. A negative urine or serum pregnancy test within the two week interval immediately prior to imaging, in women of child-bearing age. Ability to provide written informed consent to participate in the study (for all components of the trial: imaging with cardiac PET/MR, blood sampling for plasma metabolomics and circulating DNA). Exclusion Criteria: Contraindication for MR as per current institutional guidelines. Contraindication for Gadolinium injection as per current institutional guidelines. Inability to lie supine for at least 45 minutes. Any patient who is pregnant or breastfeeding. Any patient with known hypersensitivity to 18F-FDG.