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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new imaging method to help doctors detect prostate cancer that may have spread to the lymph nodes. The study uses a special substance called 99mTc-PSMA-I&S (Technetium-99m PSMA Imaging and Surgery Agent), injected before surgery to highlight cancerous areas during the operation. The trial seeks men with prostate cancer who have undergone a specific scan (68Ga-PSMA-11 PET/CT) indicating potential cancer spread to the lymph nodes and are scheduled for pelvic lymph node removal surgery. As an Early Phase 1 trial, this research aims to understand how this new imaging method works in people, offering participants the chance to be among the first to benefit from this innovative approach.

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 prior data suggests that this imaging technique is safe for prostate cancer patients?

Research has shown that 99mTc-PSMA-I&S helps locate prostate cancer in lymph nodes during surgery. Previous patients found this method safe and manageable, with minimal radiation exposure. Studies have not identified any major side effects, suggesting it is a safe option for those considering trials with this imaging and surgery method. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about 99mTc-PSMA Imaging for prostate cancer because it offers a new way to precisely locate cancer cells. Unlike traditional imaging methods, this technique uses a special radioactive tracer, 99mTc-PSMA, which targets the PSMA protein found abundantly on prostate cancer cells. This targeted approach enables more accurate imaging of cancer spread, potentially leading to better surgical outcomes. Moreover, the integration of SPECT/CT scans provides detailed 3D images, which can help doctors plan more effective treatments.

What evidence suggests that this imaging technique is effective for detecting prostate cancer?

Research has shown that 99mTc-PSMA imaging, which participants in this trial will receive, is promising for detecting prostate cancer that has spread to the lymph nodes. This technique uses a special marker that attaches to prostate cancer cells, making them visible during surgery. Studies have demonstrated that it effectively highlights even small cancerous areas that are often difficult to detect. Initial patient data suggest this method is at least as effective, if not better, than some existing techniques for locating cancer. Additionally, it is considered a cost-effective and easily accessible option. ^{1 4 6 7 8}

Who Is on the Research Team?

Jeremie Calais

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10798073/

Diagnostic value of [99mTc]Tc-PSMA-I&S-SPECT/CT for ... The aim of this study was to evaluate the performance of [99mTc]Tc-PSMA-I&S (for imaging and surgery) in prostate cancer. Design and methods: We ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04857502

99mTc-PSMA-I&S Biodistribution in Patients With Prostate ... 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 ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/58/2/235

Preclinical Evaluation and First Patient Application of 99m Tc ... 99m Tc-PSMA-I&S represents a cost-effective, readily available alternative to 111 In-PSMA-I&T. Initial patient data indicate its comparable or even superior ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666168323002549

State of the Art in Prostate-specific Membrane Antigen– ... In this paper, we review recent advances in prostate–specific membrane antigen (PSMA)-targeted surgery, which is used to help identify and remove prostate ...

5. nature.com nature.com/articles/s41598-022-20280-x

Head-to-head comparison of 99m Tc-PSMA and ... - Nature 99m Tc-PSMA SPECT/CT was superior to 99m Tc-MDP SPECT/CT in the detection of bone metastases in PCa, especially for small lesions and in patients with low PSA ...

6. jnm.snmjournals.org jnm.snmjournals.org/content/62/8/1075

Radiation Dosimetry of 99m Tc-PSMA I&S: A Single-Center ... 99m Tc-PSMA I&S is a prostate-specific membrane antigen (PSMA) tracer that can be used for planar and SPECT/CT γ-imaging and radioguided surgery.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9099988/

A Review on the Current State and Future Perspectives of ... This review aims to give a concise overview of the specific features of the developed 99m Tc Tc-tagged PSMA agents.

8. pubs.acs.org pubs.acs.org/doi/10.1021/acsptsci.4c00637

Single-Photon Emission Computer Tomography Imaging of ... The results of the Phase I study showed that injections of [99mTc]Tc-BQ0413 were well tolerated, safe, and associated with low absorbed doses.