[68Ga]CBP8 Imaging for Radiation-Induced Tissue Injury

Overseen By Shadi Esfahani, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Disqualifiers: Pacemaker, Ferromagnetic implants, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

72 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging agent, [68Ga]CBP8, to determine its effectiveness in detecting tissue damage from radiation therapy. The goal is to identify collagen buildup, which can occur after radiation treatment, particularly in patients with lung or pancreatic cancer. The trial includes two groups: lung cancer patients unsuitable for surgery and pancreatic cancer patients with a confirmed diagnosis undergoing standard treatments. This trial may suit those who have undergone or are about to undergo radiation therapy for these cancers. Participants must not have used tobacco recently and need to lie comfortably during imaging procedures. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that [68Ga]CBP8 is likely to be safe for humans?

Research has shown that the treatment, called \[68Ga\]CBP8, has been safely tested in people. In an earlier study, nine healthy volunteers received \[68Ga\]CBP8, and none experienced negative side effects, suggesting the treatment is well-tolerated. \[68Ga\]CBP8 serves as a special imaging tool, allowing doctors to examine the body without surgery. Based on the research so far, it appears safe for use in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for radiation-induced tissue injury focus on managing symptoms after the damage has occurred. But [68Ga]CBP8 is different because it aims to detect tissue injury early using PET imaging. This treatment uses a special imaging agent, [68Ga]CBP8, which helps visualize areas of injury caused by radiation therapy in lung and pancreatic cancer patients. Researchers are excited because this could lead to earlier intervention and potentially better outcomes by allowing doctors to see the damage before symptoms even appear.

What evidence suggests that [68Ga]CBP8 is effective for detecting radiation-induced tissue injury?

Research has shown that [68Ga]CBP8 effectively detects collagen buildup in damaged tissues following radiation therapy. This buildup, known as fibrosis, often occurs after such treatments. Studies have found that [68Ga]CBP8 specifically attaches to type I collagen, which plays a major role in fibrosis. Early tests on lung tissue damaged by radiation are promising, as the probe successfully identifies areas of collagen accumulation. This trial will involve lung or pancreatic cancer patients receiving [68Ga]CBP8 to visualize and measure tissue damage before and after radiation therapy. ^{1 2 6 7 8}

Who Is on the Research Team?

Michael Lanuti, MD

Principal Investigator

Massachusetts General Hospital

Shadi Esfahani, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults with a life expectancy over 3 months who have certain types of cancer (like lung or pancreatic) and are not using tobacco. They must be able to consent, fit within MRI weight limits, and not have metal implants or severe claustrophobia. Pregnant women can't participate.

Inclusion Criteria

I am receiving chemotherapy and radiotherapy as initial treatment based on my hospital's standards.

I have an appointment before starting my pre-surgery cancer treatment.

My lung cancer is at an advanced stage but cannot be removed by surgery.

Exclusion Criteria

I cannot lie comfortably on my back for scans due to my pancreatic cancer.

I have been exposed to more than the recommended amount of radiation for pancreatic cancer research.

I am claustrophobic and have pancreatic cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Radiation PET Imaging

Participants receive [68Ga]CBP8 and undergo PET imaging prior to radiation therapy

1 week

1 visit (in-person)

Radiation Therapy

Participants undergo radiation therapy as part of their standard cancer treatment

6-8 weeks

Post-Radiation PET Imaging

Participants receive [68Ga]CBP8 and undergo PET imaging 3-6 months after radiation therapy to detect collagen deposition

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3-6 months

What Are the Treatments Tested in This Trial?

Interventions

• [68Ga]CBP8

Trial Overview [68Ga]CBP8 is being tested to see if it's effective in detecting collagen in tissues damaged by radiation. Participants will undergo PET-MRI scans with this probe to assess its efficacy.

How Is the Trial Designed?

Group I: Lung Cancer or Pancreatic Cancer Subjects Undergoing Radiation Therapy Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Radiation can enhance the targeting of drugs to tumors by inducing the expression of specific molecules, particularly the beta(3) integrin, which allows for better site-specific binding of therapeutic peptides and antibodies.

In a clinical trial, the RGD peptidomimetic biapcitide labeled with 99mTc demonstrated the feasibility of using radiation-guided peptides to direct drug delivery to human tumors, indicating a promising approach for improving cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting drug delivery to radiation-induced neoantigens in tumor microvasculature. Hallahan, DE., Geng, L., Cmelak, AJ., et al.[2019]

The new PET tracer (64)Cu-NODAGA-c(RGDyK) shows strong potential for imaging tumor angiogenesis, with significant correlations between tracer uptake and gene expression of angiogenesis markers in human neuroendocrine tumor xenografts, indicating its efficacy in targeting tumors.

Estimated radiation doses for humans are low, at 0.038 mSv/MBq for females and 0.029 mSv/MBq for males, suggesting that (64)Cu-NODAGA-c(RGDyK) is safe for potential clinical use, with the highest dose absorbed by the bladder wall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(64)Cu-NODAGA-c(RGDyK) Is a Promising New Angiogenesis PET Tracer: Correlation between Tumor Uptake and Integrin α(V)β(3) Expression in Human Neuroendocrine Tumor Xenografts. Oxboel, J., Schjoeth-Eskesen, C., El-Ali, HH., et al.[2021]

The study developed a collagen-targeted PET probe, 64Cu-CBP7, which showed significantly higher uptake in the lungs of mice with bleomycin-induced pulmonary fibrosis compared to healthy controls, indicating its potential for early detection of lung fibrosis.

64Cu-CBP7 demonstrated superior metabolic stability and specificity for collagen, making it a promising candidate for noninvasive imaging of pulmonary fibrosis progression in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of a Collagen-Targeted PET Probe for Molecular Imaging of Pulmonary Fibrosis. Désogère, P., Tapias, LF., Rietz, TA., et al.[2020]

The peptide-based PET probe 68Ga-CBP8 specifically targets collagen type I and shows high specificity for pulmonary fibrosis in a mouse model, indicating its potential for noninvasive imaging of this condition.

In vivo and ex vivo studies demonstrated a strong correlation between 68Ga-CBP8 uptake and lung collagen levels, suggesting it could effectively monitor treatment responses in pulmonary fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. Désogère, P., Tapias, LF., Hariri, LP., et al.[2018]

The 68Ga-Collagen Binding Probe #8 (68Ga-CBP8) was safely administered to nine healthy volunteers, showing no adverse effects and demonstrating favorable biodistribution with rapid renal clearance.

This probe has potential for noninvasive imaging of tissue fibrosis, with pharmacokinetics indicating a quick initial distribution and a longer elimination phase, making it suitable for assessing fibrotic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8: A Type I Collagen-Targeted PET Probe. Izquierdo-Garcia, D., Désogère, P., Fur, ML., et al.[2023]

CBP1495 is a newly identified collagen-binding peptide that effectively targets collagen type I, showing strong binding affinity and potential for use in imaging fibrosis.

The 99mTc-labelled version of CBP1495 demonstrated significant accumulation in fibrotic tissues in rat models, indicating its potential as a non-invasive radiotracer for diagnosing and monitoring fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular imaging of fibrosis using a novel collagen-binding peptide labelled with 99mTc on SPECT/CT. Zheng, L., Ding, X., Liu, K., et al.[2018]

The study demonstrated that (18)F-RGD PET/CT imaging can effectively visualize glioblastoma multiforme (GBM) lesions and predict patient sensitivity to concurrent chemoradiotherapy (CCRT) within just 3 weeks of treatment initiation, based on a cohort of 25 patients.

Key parameters from (18)F-RGD PET/CT, particularly the intratreatment SUVmax at 3 weeks, were found to be strong predictors of treatment response, with a sensitivity of 84.6% and specificity of 90.0%, indicating its potential as a valuable tool in assessing treatment efficacy early in the therapy process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can an ¹⁸F-ALF-NOTA-PRGD2 PET/CT Scan Predict Treatment Sensitivity to Concurrent Chemoradiotherapy in Patients with Newly Diagnosed Glioblastoma? Zhang, H., Liu, N., Gao, S., et al.[2017]

An improved collagelin analogue labeled with gallium-68 for PET imaging shows promise for non-invasive and sensitive assessment of fibrosis, achieving a high radiochemical purity of 98% and stable performance for at least 3 hours.

In studies with mice, the new imaging agent demonstrated specific binding to fibrotic liver tissue, correlating well with fibrosis severity, and exhibited a safe dosimetry profile allowing for multiple PET scans per year.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Radiolytic Stability of a 68Ga-labelled Collagelin Analogue for the Imaging of Fibrosis. Velikyan, I., Rosenström, U., Rosestedt, M., et al.[2021]

Both (68)Ga-NODAGA-E[c(RGDyK)](2) and (64)Cu-NODAGA-E[c(RGDyK)](2) are effective PET tracers for imaging tumor angiogenesis, showing similar uptake in human xenograft tumors in mice, which suggests their potential for clinical use.

(68)Ga-NODAGA-E[c(RGDyK)](2) demonstrated slightly better tumor retention and can be synthesized using in-house generators, making it a more practical option for future clinical PET imaging in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of two new angiogenesis PET tracers 68Ga-NODAGA-E[c(RGDyK)]2 and (64)Cu-NODAGA-E[c(RGDyK)]2; in vivo imaging studies in human xenograft tumors. Oxboel, J., Brandt-Larsen, M., Schjoeth-Eskesen, C., et al.[2022]

Engineered nanoparticles that target collagen IV can effectively identify early-stage blood vessel injuries caused by high-dose radiotherapy, highlighting their potential for monitoring radiation-induced damage.

These nanoparticles are designed to specifically bind to the basement membrane, which may enhance their ability to detect vascular injuries early in the treatment process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct Observation of Early-Stage High-Dose Radiotherapy-Induced Vascular Injury via Basement Membrane-Targeting Nanoparticles. Au, KM., Hyder, SN., Wagner, K., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04485286

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

2. jnm.snmjournals.org jnm.snmjournals.org/content/64/5/775

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8 The aim of this study was to determine the biodistribution, dosimetry, and pharmacokinetics of 68 Ga-CBP8 in healthy human subjects.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03535545

Preliminary Evaluation of [68Ga]CBP8 in Healthy ... The goal of this study is to investigate the safety of [68Ga]CBP8 and its efficacy to detect collagen deposition in pulmonary fibrosis. Detailed Description.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37116909/

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8 The 68 Ga-Collagen Binding Probe #8, 68 Ga-CBP8, is a peptide-based, type I collagen-targeted probe developed for imaging of tissue fibrosis.

5. medrxiv.org medrxiv.org/content/medrxiv/early/2023/09/26/2023.09.25.23295897.full.pdf

Noninvasive Quantification of Radiation-Induced Lung ... The human analog probe targeted against type 1 collagen, 68Ga-CBP8, was tested on excised human lung tissue containing RILI and quantified via ...

6. withpower.com withpower.com/trial/phase-3-pancreatic-neoplasms-1-2021-ce8c4

[68Ga]CBP8 Imaging for Radiation-Induced Tissue Injury The 68Ga-Collagen Binding Probe #8 (68Ga-CBP8) was safely administered to nine healthy volunteers, showing no adverse effects and demonstrating favorable ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10152126/

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga ... The 68Ga-Collagen Binding Probe #8, 68Ga-CBP8, is a peptide-based, type I collagen–targeted probe developed for imaging of tissue fibrosis.

8. ctv.veeva.com ctv.veeva.com/study/evaluation-of-pet-probe-68ga-cbp8-in-the-detection-of-radiation-induced-tissue-injury

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