99mTc-PSMA Imaging for Prostate Cancer

Overseen By Deepu Varughese

Age: Any Age

Sex: Male

Trial Phase: Phase < 1

Sponsor: Jonsson Comprehensive Cancer Center

Disqualifiers: Pca treatment, Inaccessible nodal location

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: 6

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you start any prostate cancer treatment between enrollment and surgery, you will be excluded from the trial.

What data supports the effectiveness of the treatment 99mTc-PSMA-I&S for prostate cancer?

Research shows that 99mTc-PSMA-I&S is effective in imaging prostate cancer, helping to identify and locate cancer spread to lymph nodes, which can guide surgery. This imaging agent targets a protein commonly found on prostate cancer cells, making it a valuable tool for diagnosing and managing the disease. ^{1 2 3 4 5}

Is 99mTc-PSMA Imaging for Prostate Cancer safe for humans?

In a study with healthy volunteers and prostate cancer patients, 99mTc-PSMA Imaging showed no adverse events related to its injection, suggesting it is generally safe for human use. ^{2 6 7 8 9}

How is the drug 99mTc-PSMA-I&S unique for prostate cancer treatment?

99mTc-PSMA-I&S is unique because it is a technetium-99m labeled tracer specifically designed for both imaging and guiding surgery in prostate cancer, offering an alternative to PET imaging in areas where PET is not available. It provides high tumor-to-background ratios, making it effective for detecting cancerous lesions with lower radiation doses compared to other tracers like 68Ga and 18F. ^{2 9 10 11 12}

What is the purpose of this trial?

This exploratory study conducted under the RDRC program studies the biodistribution of 99mTc-PSMA-I\&S in patients with prostate cancer who undergo pelvic lymph node dissection. Prostate specific membrane antigen (PSMA)-targeted radio-guided surgery uses the preoperative intravenous administration of a PSMA-ligand called PSMA-imaging and surgery (I\&S) labeled with the gamma-emitter radioisotope Technetium-99m (99mTc). Giving 99mTc-PSMA-I\&S may detect PSMA-expressing lymph nodes during surgery using a gamma probe and may help guide doctors to detect prostate cancer that has spread to the lymph nodes.

Research Team

Jeremie Calais

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Eligibility Criteria

This trial is for men with prostate cancer (new or recurring) who are set to have surgery to remove lymph nodes in the pelvis. They must show positive lymph node disease on a specific PET/CT scan and be able to follow study procedures. Men already treated for prostate cancer between enrollment and surgery, or with hard-to-reach nodal locations can't join.

Inclusion Criteria

I am a man with prostate cancer (either newly diagnosed or recurrent).

I am a man who can understand and agree to the study's terms.

I am a man scheduled for surgery to remove lymph nodes in my pelvis.

Exclusion Criteria

My cancer has spread to a place doctors can't easily reach.

I started prostate cancer treatment between joining the study and surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Imaging and Surgery Preparation

The first 5 patients receive an initial dose of 99mTc-PSMA-I&S intravenously followed by 5 SPECT/CT scans at specified intervals.

2 days

5 visits (in-person)

Surgery

Patients undergo standard of care surgery after receiving 99mTc-PSMA-I&S.

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after surgery.

4 weeks

Treatment Details

Interventions

• 99mTc-based PSMA Imaging and Surgery Agent

Trial Overview The study tests a new method using an imaging agent called 99mTc-PSMA-I&S during surgery to see if it helps find and guide the removal of cancerous lymph nodes by emitting a signal that doctors can detect with special equipment.

Participant Groups

Group I: Diagnostic (99mTc-PSMA-I&S, SPECT/CT) Experimental Treatment 3 Interventions

The first 5 patients receive an initial dose of undergo 99mTc-PSMA-I\&S IV followed by 5 SPECT/CT scans at 3-5, 5-20, 17-21, 25-29, and 40-46 hours later. These 5 patients then receive a second dose of 99mTc-PSMA-I\&S IV and then undergo standard of care surgery. All subsequent patients receive one dose of 99mTc-PSMA-I\&S IV before standard of care surgery.

99mTc-based PSMA Imaging and Surgery Agent is already approved in European Union, United States for the following indications:

Approved in European Union as 99mTc-PSMA-I&S for:

• Primary staging of prostate cancer
• Biochemical recurrence of prostate cancer
• Detection of prostate cancer metastases

Approved in United States as 99mTc-PSMA-I&S for:

• Primary staging of prostate cancer
• Biochemical recurrence of prostate cancer
• Detection of prostate cancer metastases

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Findings from Research

The study of 54 prostate cancer patients demonstrated that 99mTc-labeled PSMA SPECT/CT imaging significantly improved the detection of lymph node metastases, identifying 52 suspicious nodes with high sensitivity and specificity, which conventional MRI missed in some cases.

Patients who underwent surgery guided by PSMA SPECT/CT had better biochemical responses in terms of prostate-specific antigen (PSA) levels compared to those who had standard lymph node dissection, indicating that this imaging technique can enhance surgical outcomes and potentially delay disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Value of 99mTc-PSMA SPECT/CT-Guided Surgery for Identifying and Locating Lymph Node Metastasis in Prostate Cancer Patients. Su, HC., Zhu, Y., Hu, SL., et al.[2019]

In a study involving 210 prostate cancer patients, [99mTc]Tc-PSMA-I&S-SPECT/CT demonstrated a 65.2% detection rate for PSMA-positive lesions, particularly effective at higher PSA levels, with detection rates reaching 100% at PSA levels above 10 ng/ml.

While [99mTc]Tc-PSMA-I&S-SPECT/CT is useful for imaging at various stages of prostate cancer, its effectiveness is significantly lower at PSA levels below 4 ng/ml compared to PET imaging, suggesting it should be used when PET is not available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[99cmTc]Tc-PSMA-I&amp;S-SPECT/CT: experience in prostate cancer imaging in an outpatient center. Werner, P., Neumann, C., Eiber, M., et al.[2023]

PSMA-targeted imaging and therapeutics are emerging as promising tools for improving the management of various stages of prostate cancer, including primary, recurrent, and metastatic cases.

A multidisciplinary approach involving nuclear radiology, medical oncology, urology, and radiation oncology is essential to fully realize the potential benefits of PSMA theranostics in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incorporating PSMA-Targeting Theranostics Into Personalized Prostate Cancer Treatment: a Multidisciplinary Perspective. Ng, TSC., Gao, X., Salari, K., et al.[2022]

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]

Prostate-specific membrane antigen (PSMA) is a key target for imaging prostate cancer, enabling noninvasive diagnostic techniques like PSMA-PET and assisting in the surgical removal of cancerous lesions.

The review highlights various PSMA-targeted tracers, discussing how their chemical properties influence their effectiveness in imaging and guiding surgery, which is crucial for improving treatment outcomes in prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-Guided Surgery: Are We Getting the Most Out of Small-Molecule Prostate-Specific-Membrane-Antigen-Targeted Tracers? Hensbergen, AW., van Willigen, DM., van Beurden, F., et al.[2023]

The PET tracer 18F-PSMA 1007 was found to be safe and well tolerated in both healthy volunteers and prostate cancer patients, with no serious adverse events reported during the study.

In terms of diagnostic effectiveness, 18F-PSMA 1007 demonstrated high accuracy in detecting prostate cancer, achieving a sensitivity of 80% and a positive predictive value of 100% in patients with untreated preoperative prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/IIa trial of 18F-prostate specific membrane antigen (PSMA) 1007 PET/CT in healthy volunteers and prostate cancer patients. Tateishi, U., Kimura, K., Tsuchiya, J., et al.[2023]

The new 211At-labeled radiotracer, 211At-3-Lu, effectively targets prostate-specific membrane antigen (PSMA) in prostate cancer cells, showing significant uptake in PSMA+ tumors with minimal uptake in non-target cells, indicating its potential for targeted therapy.

In a long-term toxicity study, 211At-3-Lu demonstrated low off-target toxicity and favorable safety profiles, including stable hematopoietic function and positive histopathological outcomes, suggesting it could be a safe and effective treatment option for patients with prostate cancer resistant to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Improved 211At-Labeled Agent for PSMA-Targeted &#945;-Therapy. Mease, RC., Kang, CM., Kumar, V., et al.[2022]

The novel 68Ga-THP PSMA PET/CT imaging technique was found to be safe for use in prostate cancer patients, with no serious adverse events reported and only minor side effects observed in two patients.

This imaging method led to a change in clinical management for 42.9% of the patients evaluated, indicating its potential effectiveness in guiding treatment decisions for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II, Open-label study to assess safety and management change using 68Ga-THP PSMA PET/CT in patients with high risk primary prostate cancer or biochemical recurrence after radical treatment: The PRONOUNCED study. Afaq, A., Payne, H., Davda, R., et al.[2022]

The study found that 99mTc-PSMA I&S has a low effective radiation dose, comparable to other 99mTc tracers, making it a safe option for imaging in prostate cancer patients, with no reported adverse events in healthy volunteers.

In patients with prostate cancer, 99mTc-PSMA I&S demonstrated high tumor-to-background ratios, indicating effective localization of the tracer in both primary and metastatic lesions, which supports its potential for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Dosimetry of 99mTc-PSMA I&amp;S: A Single-Center Prospective Study. Urbán, S., Meyer, C., Dahlbom, M., et al.[2022]

The novel imaging tracer [99mTc]Tc-HYNIC-PSMA-XL-2 is safe and effectively targets prostate cancer lesions, including primary tumors and metastases in lymph nodes and bones, as demonstrated in preliminary clinical applications with multiple patients.

The tracer is primarily cleared through the hepatobiliary and intestinal systems, with a half-life of about 3.90 hours, and shows high absorbed doses in salivary glands, kidneys, and spleen, indicating its specific localization and potential for effective imaging without bladder interference.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetry estimation and preliminary clinical application of [99mTc]Tc-HYNIC-PSMA-XL-2 in prostate cancer. Yang, H., Gao, Z., Xu, X., et al.[2023]

In a study of 17 patients undergoing robotic-assisted surgery for prostate cancer, significant heterogeneity in prostate-specific membrane antigen (PSMA) expression was found, with PSMA-negative areas present in all samples, indicating potential limitations for imaging and treatment.

Higher PSMA-ligand uptake was associated with higher Gleason scores (GS ≥ 8), particularly with Gleason Pattern 4, suggesting that PSMA-ligand imaging could be a useful noninvasive biomarker for identifying high-grade prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterogeneity of prostate-specific membrane antigen (PSMA) and PSMA-ligand uptake detection combining autoradiography and postoperative pathology in primary prostate cancer. Wang, H., Remke, M., Horn, T., et al.[2023]

The automated synthesis of [99mTc]Tc-PSMA-I&S for prostate cancer diagnostics achieved a stable radiochemical yield of 58.7% and high purity of 93%, indicating its potential effectiveness as a diagnostic tool.

This process adheres to good manufacturing practice (GMP) standards, demonstrating reliability and applicability for clinical use, which is important given the lack of commercially approved kits for this tracer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of in-House Synthesis and Quality Control of [99mTc]Tc-PSMA-I&amp;S. Plhak, E., Pichler, C., Gößnitzer, E., et al.[2023]

References

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

The Value of 99mTc-PSMA SPECT/CT-Guided Surgery for Identifying and Locating Lymph Node Metastasis in Prostate Cancer Patients. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

[99cmTc]Tc-PSMA-I&amp;S-SPECT/CT: experience in prostate cancer imaging in an outpatient center. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Incorporating PSMA-Targeting Theranostics Into Personalized Prostate Cancer Treatment: a Multidisciplinary Perspective. [2022]

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

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

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

Image-Guided Surgery: Are We Getting the Most Out of Small-Molecule Prostate-Specific-Membrane-Antigen-Targeted Tracers? [2023]

6. England pubmed.ncbi.nlm.nih.gov

Phase I/IIa trial of 18F-prostate specific membrane antigen (PSMA) 1007 PET/CT in healthy volunteers and prostate cancer patients. [2023]

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

An Improved 211At-Labeled Agent for PSMA-Targeted &#945;-Therapy. [2022]

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

A Phase II, Open-label study to assess safety and management change using 68Ga-THP PSMA PET/CT in patients with high risk primary prostate cancer or biochemical recurrence after radical treatment: The PRONOUNCED study. [2022]

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

Radiation Dosimetry of 99mTc-PSMA I&amp;S: A Single-Center Prospective Study. [2022]

10. Japan pubmed.ncbi.nlm.nih.gov

Dosimetry estimation and preliminary clinical application of [99mTc]Tc-HYNIC-PSMA-XL-2 in prostate cancer. [2023]

11. Germany pubmed.ncbi.nlm.nih.gov

Heterogeneity of prostate-specific membrane antigen (PSMA) and PSMA-ligand uptake detection combining autoradiography and postoperative pathology in primary prostate cancer. [2023]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Development of in-House Synthesis and Quality Control of [99mTc]Tc-PSMA-I&amp;S. [2023]