PET Imaging for Breast Cancer

Overseen By Ahmad Shariftabrizi, M.D.

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Ahmad Shariftabrizi

Disqualifiers: Other malignancy, Pregnancy, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment PSMA-based radionuclide therapy, Lutetium-177 PSMA-617, and 68Ga-PSMA-11 PET/CT for breast cancer?

While there is no direct data on the effectiveness of this treatment for breast cancer, PSMA-based radionuclide therapy with Lutetium-177 PSMA-617 has shown promising results in improving survival rates in patients with advanced prostate cancer. This suggests potential effectiveness in targeting cancer cells, which could be relevant for breast cancer treatment. ^{1 2 3 4 5}

Is Lutetium-177 PSMA-617 safe for humans?

Lutetium-177 PSMA-617 has been used safely in patients with prostate cancer, even in those with a single functioning kidney, although there is potential for kidney-related side effects due to its excretion through the kidneys. ^{6 7 8 9 10}

How is PSMA-based radionuclide therapy different from other breast cancer treatments?

PSMA-based radionuclide therapy is unique because it uses a radioactive substance, Lutetium-177, attached to a molecule that specifically targets the PSMA protein, which is more commonly associated with prostate cancer. This approach allows for precise delivery of radiation to cancer cells, potentially offering a new treatment option for breast cancer if PSMA is present. ^{1 2 11 12 13}

What is the purpose of this trial?

The purpose of this research is to determine the expression of Prostate Specific Membrane Antigen(PSMA) in metastatic Triple Negative Breast Cancer (TNBC) patients using Fludeoxyglucose F18 (FDG) PET/CT as the gold standard. The investigators hypothesize that most lesions in metastatic TNBC are PSMA-avid; and thus PSMA-based radionuclide therapy can be a valid treatment option for TNBC, and clinical trials can be designed for this purpose. Thirty metastatic TNBC patients will be enrolled and will be on the study for maximum of 4 weeks.

Eligibility Criteria

This trial is for women aged 18 or older with metastatic Triple Negative Breast Cancer (TNBC) confirmed by biopsy. Participants must have FDG-positive metastatic lesions visible on an initial PET/CT scan. It's not suitable for those with other active cancers, who can't tolerate a PET/CT procedure, or are pregnant/breastfeeding.

Inclusion Criteria

I am a woman aged 18 or older.

Patient should have FDG positive metastatic lesions on the initial PET/CT scan performed in this study to be further included

My initial biopsy shows that my triple-negative breast cancer has spread to distant areas.

Exclusion Criteria

Patients with any medical condition that might compromise the safety of subject during PET acquisitions

I have another active cancer besides the one being treated.

Unable to tolerate PET/CT procedure

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

PET Imaging

Participants undergo FDG PET/CT and 18F-DCFPyL-PET/CT imaging to evaluate PSMA expression

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

2 weeks

Treatment Details

Interventions

• PSMA-based radionuclide therapy

Trial Overview The study aims to assess the presence of Prostate Specific Membrane Antigen (PSMA) in metastatic TNBC using Fludeoxyglucose F18 (FDG) PET/CT scans as a reference. The goal is to explore PSMA-based treatments and design future trials based on these findings.

Participant Groups

Group I: PET Imaging Experimental Treatment 1 Intervention

Triple negative breast cancer patients will undergo FDG PET/CT and Pyl PET/Ct

PSMA-based radionuclide therapy is already approved in United States, European Union for the following indications:

Approved in United States as Lutetium-177 PSMA-617 for:

• Prostate cancer

Approved in United States as 68Ga-PSMA-11 PET/CT for:

• Prostate cancer

Approved in European Union as Lutetium-177 PSMA-617 for:

• Prostate cancer

Who Is Running the Clinical Trial?

Ahmad Shariftabrizi

Lead Sponsor

Trials

1

Recruited

30+

Progenics Pharmaceuticals, Inc.

Industry Sponsor

Trials

35

Recruited

4,400+

Findings from Research

PSMA-targeted imaging and therapy have significantly improved the management of prostate cancer, particularly in advanced stages like metastasized castration-resistant prostate cancer.

Lutetium-177-conjugated PSMA-617 or PSMA-I&T (Lu-PSMA) has shown promising results in both multicenter retrospective and monocenter prospective trials, indicating its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate Cancer Theranostics: PSMA Targeted Therapy. Seifert, R., Alberts, IL., Afshar-Oromieh, A., et al.[2021]

PSMA-targeted PET/CT imaging has shown superior detection rates for prostate cancer compared to older imaging methods, making it valuable for initial staging and restaging during biochemical recurrence.

Radioligand therapy (RLT) using Lutetium-177 (177Lu) linked to PSMA antibodies has been associated with improved overall survival rates in patients with metastatic castration-resistant prostate cancer, indicating its efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting PSMA Revolutionizes the Role of Nuclear Medicine in Diagnosis and Treatment of Prostate Cancer. Luining, WI., Cysouw, MCF., Meijer, D., et al.[2022]

In a study of seven patients with progressive prostate cancer, (177)Lu-PSMA-617 therapy was found to be safe, with the highest radiation doses absorbed by the parotid glands (1.17 mGy/MBq) and kidneys (0.88 mGy/MBq), while the bone marrow received a significantly lower dose (0.03 mGy/MBq).

The findings suggest that the parotid glands are the dose-limiting organs in this therapy, indicating that individual patient dosimetry is essential due to substantial variations in radiation absorption among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-therapeutic dosimetry of normal organs and tissues of (177)Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer. Kabasakal, L., AbuQbeitah, M., Aygün, A., et al.[2021]

In a study of 135 prostate cancer patients, those with high tumor loads showed significantly reduced uptake of Ga-68-PSMA-11 in critical organs like the lacrimal and salivary glands, which could impact treatment planning for radioligand therapy (RLT).

The findings suggest that individualizing therapy protocols based on diagnostic PSMA PET imaging could enhance the efficacy and safety of Lu-177-labeled PSMA-ligand therapy, as reduced tracer uptake in dose-limiting organs may affect treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uptake of PSMA-ligands in normal tissues is dependent on tumor load in patients with prostate cancer. Gaertner, FC., Halabi, K., Ahmadzadehfar, H., et al.[2018]

In a study of 71 patients with metastatic castration-resistant prostate cancer, 56% experienced a significant PSA decline of 50% or more after receiving three cycles of Lutetium-177 labeled PSMA-617 radioligand therapy, indicating its efficacy as a treatment option.

The therapy demonstrated delayed responses, as 28 out of 30 patients who responded after the first cycle continued to show positive results, and 12 out of 41 initial non-responders responded to subsequent cycles, highlighting the potential for ongoing therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed response after repeated 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration resistant prostate cancer. Rahbar, K., Bögeman, M., Yordanova, A., et al.[2021]

Lutetium-177 PSMA-617 (Lu-177-PSMA-617) has been approved by the FDA for treating patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have already undergone other treatments, indicating its efficacy in a specific patient population.

The paper outlines essential logistical and safety considerations for implementing a radiopharmaceutical therapy program, emphasizing the importance of developing proper operating procedures for administering Lu-177-PSMA-617 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Logistical, technical, and radiation safety aspects of establishing a radiopharmaceutical therapy program: A case in Lutetium-177 prostate-specific membrane antigen (PSMA) therapy. Zoberi, JE., Garcia-Ramirez, J., Luechtefeld, D., et al.[2023]

In a study of 75 patients with metastatic prostate cancer, 6 were excluded from Lutetium-177 [177Lu]-PSMA-617 treatment due to PSMA-negative/FDG-positive discordance, but 89 suitable targets for biology-guided radiotherapy (BgRT) were identified.

The research suggests that combining BgRT with Lutetium-177 [177Lu]-PSMA-617 is feasible for treating patients with discordant metastases, particularly highlighting that bone and lung metastases are the most suitable candidates for this combined therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer. Gaudreault, M., Chang, D., Hardcastle, N., et al.[2023]

Pre-clinical studies indicate that the specific activity of lutetium-177 does not significantly affect the overall tumor uptake of the PSMA-targeted radiopharmaceutical 177Lu-PSMA-617, suggesting consistent efficacy in targeting cancer cells.

However, the tumor-to-non-target organ ratios were improved with carrier added lutetium-177, indicating that while specific activity may not influence uptake, it can enhance the safety profile by reducing radiation exposure to healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo response of PSMA-617 radiolabeled with CA and NCA lutetium-177. Wieczorek Villas Boas, CA., de Jesus Silva, J., Pereira Dias, LA., et al.[2022]

In a study involving 145 patients with metastatic castration-resistant prostate cancer (mCRPC), treatment with 177Lu-PSMA-617 showed a biochemical response rate of 45%, indicating high efficacy, especially with 40% of patients responding after just one treatment cycle.

The therapy demonstrated a favorable safety profile, with only 10% of patients experiencing severe hematotoxicity and 8% reporting dry mouth, suggesting it may be a safer option compared to other third-line treatments for mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. Rahbar, K., Ahmadzadehfar, H., Kratochwil, C., et al.[2022]

177Lu PSMA-617 Radio-ligand Therapy is a promising treatment for metastatic castration-resistant prostate carcinoma, but it poses potential renal toxicity due to its excretion through the kidneys.

This case report highlights the renal safety of administering multiple doses of 177Lu PSMA-617 in a patient with a solitary-functioning kidney, suggesting that it can be safely used even in patients with compromised renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium-177 Prostate Specific Membrane Antigen Therapy in a Patient With Double Malignancy and Single Functioning Kidney: A Case Report. Naeem, Z., Zahra, UB., Numair Younis, M., et al.[2023]

The study successfully converted a gallium-68 imaging agent into a lutetium-177 therapeutic agent for prostate cancer, demonstrating strong PSMA binding affinity comparable to the FDA-approved [177Lu]Lu-PSMA-617.

Biodistribution studies in mice showed that the new agent [177Lu]Lu-7 had a longer blood half-life and higher tumor uptake than both [177Lu]Lu-4 and [177Lu]Lu-PSMA-617, indicating its potential for improved therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177). Zha, Z., Choi, SR., Li, L., et al.[2022]

A 76-year-old man with advanced prostate cancer showed significant improvement after treatment with lutetium 177 PSMA-617, indicating its potential efficacy in patients resistant to standard therapies.

The treatment led to marked biochemical and imaging responses, as well as improvements in clinical status and pain relief, highlighting the therapeutic benefits of PSMA-targeted nuclear medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-Prostate-specific Membrane Antigen Radioligand Therapy in Patients with Metastatic Castration-resistant Prostate Cancer. Parihar, AS., Hofman, MS., Iravani, A.[2023]

Prostate-specific membrane antigen (PSMA) is a promising target for developing radiopharmaceuticals in treating aggressive prostate cancers, with ongoing clinical trials focusing on PSMA-targeted therapies, particularly using the β-particle-emitting radioisotope 177Lu.

PSMA PET imaging is crucial for evaluating tumor PSMA expression, helping to select the right patients for PSMA-targeted therapies, and studies are exploring PET parameters as predictive and prognostic biomarkers for treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of PET to Appropriately Select Patients for PSMA-Targeted Theranostics. Eshghi, A., Covington, MF., Eshghi, N., et al.[2023]

References

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

Prostate Cancer Theranostics: PSMA Targeted Therapy. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting PSMA Revolutionizes the Role of Nuclear Medicine in Diagnosis and Treatment of Prostate Cancer. [2022]

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

Pre-therapeutic dosimetry of normal organs and tissues of (177)Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer. [2021]

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

Uptake of PSMA-ligands in normal tissues is dependent on tumor load in patients with prostate cancer. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

Delayed response after repeated 177Lu-PSMA-617 radioligand therapy in patients with metastatic castration resistant prostate cancer. [2021]

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

Logistical, technical, and radiation safety aspects of establishing a radiopharmaceutical therapy program: A case in Lutetium-177 prostate-specific membrane antigen (PSMA) therapy. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Combined biology-guided radiotherapy and Lutetium PSMA theranostics treatment in metastatic castrate-resistant prostate cancer. [2023]

8. England pubmed.ncbi.nlm.nih.gov

In vitro and in vivo response of PSMA-617 radiolabeled with CA and NCA lutetium-177. [2022]

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

German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. [2022]

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

Lutetium-177 Prostate Specific Membrane Antigen Therapy in a Patient With Double Malignancy and Single Functioning Kidney: A Case Report. [2023]

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

New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177). [2022]

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

177Lu-Prostate-specific Membrane Antigen Radioligand Therapy in Patients with Metastatic Castration-resistant Prostate Cancer. [2023]

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

Utility of PET to Appropriately Select Patients for PSMA-Targeted Theranostics. [2023]