Preliminary Evaluation of [68Ga]CBP8 in Healthy Individuals, Lung Cancer, and Idiopathic Pulmonary Fibrosis Patients

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 pulmonary fibrosis. The investigator's studies in
mice 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 IPF
supported the animal findings.

The investigators thus aim to perform the first in human studies of [68Ga]CBP8:

1. To evaluate the safety of [68Ga]CBP8 and its whole body distribution, metabolism,
pharmacokinetics, and radiation burden in healthy volunteers.

2. To establish the accuracy of [68Ga]CBP8-PET to detect radiation-induced fibrosis in lung
cancer patients and correlate collagen-targeted [68Ga]CBP8-PET imaging with HRCT and
histology in lung cancer patients.

3. To determine whether collagen deposition as assessed by [68Ga]CBP8-PET molecular imaging
can predict disease progression in IPF patients.

Inclusion Criteria:

- Group 1: Healthy subjects (n=5)

- Age greater than 18 years

- Be deemed healthy at screening visit as determined by the physician investigator or
nurse practitioner, based on the following assessments at Screening: physical
examination, medical history, and vital signs

- Have the ability to give written informed consent;

- No known history of pulmonary disease (excluding pulmonary nodules);

- No prior history of tobacco use.

Group 2: Lung cancer patient subjects (n=10)

- Eligible patients will be those harboring locally advanced clinical 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.

Group 3: Subjects with IPF (n=10)

- Definite IPF as defined by ATS/ERS/JRS/ALAT International Consensus Statement on IPF;

- Age: 50-80 years old;

- Have the ability to give written informed consent;

- No tobacco use within the prior 6 months

Exclusion Criteria:

- 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 for IPF in the study group), recent
pneumonia or respiratory tract infections within 6 weeks of enrollment, prior
radiation therapy to the thorax (except for the lung cancer patients in aim 2);

- Pneumonia or other acute respiratory illness within 6 weeks of study entry (except for
IPF), pneumonia defined with elevated WBC, fever, infiltrate on CXR and need for
antibiotics

Exclusion criteria specific to Group 2:

- Stage IIIA NSCLC patients who undergo definitive bimodality therapy, i.e. chemotherapy
and radiation without resection will be excluded.