[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

Trial Summary

What is the purpose of this trial?

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

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.

What data supports the effectiveness of the drug [68Ga]CBP8 for imaging radiation-induced tissue injury?

Research on similar imaging agents, like those targeting integrin β(3), shows that they can effectively bind to areas of tissue injury caused by radiation, suggesting that [68Ga]CBP8 might also be effective in identifying such injuries. ^{1 2 3 4 5}

How does the [68Ga]CBP8 treatment differ from other treatments for radiation-induced tissue injury?

[68Ga]CBP8 is unique because it is a non-invasive imaging probe that targets type I collagen, allowing for the visualization of tissue fibrosis (scarring) through PET scans. Unlike traditional treatments that may focus on managing symptoms, this probe helps in detecting and monitoring the progression of fibrosis, which is crucial for understanding the extent of radiation-induced tissue injury. ^{6 7 8 9 10}

Research Team

Michael Lanuti, MD

Principal Investigator

Massachusetts General Hospital

Shadi Esfahani, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

References

1. United States 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. [2022]

2. United States 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? [2017]

3. Germany pubmed.ncbi.nlm.nih.gov

Direct Observation of Early-Stage High-Dose Radiotherapy-Induced Vascular Injury via Basement Membrane-Targeting Nanoparticles. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Targeting drug delivery to radiation-induced neoantigens in tumor microvasculature. [2019]

5. Egypt 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. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Optimization of a Collagen-Targeted PET Probe for Molecular Imaging of Pulmonary Fibrosis. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Biodistribution, Dosimetry, and Pharmacokinetics of 68Ga-CBP8: A Type I Collagen-Targeted PET Probe. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Type I collagen-targeted PET probe for pulmonary fibrosis detection and staging in preclinical models. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Improved Radiolytic Stability of a 68Ga-labelled Collagelin Analogue for the Imaging of Fibrosis. [2021]

10. Austria pubmed.ncbi.nlm.nih.gov

Molecular imaging of fibrosis using a novel collagen-binding peptide labelled with 99mTc on SPECT/CT. [2018]