99mTc-PSMA Imaging for Prostate Cancer
Recruiting in Palo Alto (17 mi)
Age: Any Age
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Jonsson Comprehensive Cancer Center
Disqualifiers: Pca treatment, Inaccessible nodal location
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
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.
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.12345
Is 99mTc-PSMA Imaging for Prostate Cancer safe for humans?
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.29101112
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.
See 3 more
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.
Trial 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 (Radioisotope)
Trial OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: Diagnostic (99mTc-PSMA-I&S, SPECT/CT)Experimental Treatment3 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UCLA / Jonsson Comprehensive Cancer CenterLos Angeles, CA
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Who Is Running the Clinical Trial?
Jonsson Comprehensive Cancer CenterLead Sponsor
References
The Value of 99mTc-PSMA SPECT/CT-Guided Surgery for Identifying and Locating Lymph Node Metastasis in Prostate Cancer Patients. [2019]Label="BACKGROUND" NlmCategory="BACKGROUND">This study evaluated the effect of technetium-99m (99mTc)-labeled prostate-specific membrane antigen (PSMA)-based image-guided surgery on the oncologic outcomes for patients with primary or recurrent prostate cancer (PCa).
[99cmTc]Tc-PSMA-I&S-SPECT/CT: experience in prostate cancer imaging in an outpatient center. [2023]Label="BACKGROUND" NlmCategory="BACKGROUND">Prostate-specific membrane antigen (PSMA) SPECT imaging in prostate cancer (PCa) could be a valuable alternative in regions where access to PSMA-PET imaging is restricted. [99mTc]Tc-PSMA-I&S is a new 99mTc-labeled PSMA-targeting SPECT agent, initially developed for radio-guided surgery. We report on the diagnostic use of [99mTc]Tc-PSMA-I&S-SPECT/CT in PCa.
Incorporating PSMA-Targeting Theranostics Into Personalized Prostate Cancer Treatment: a Multidisciplinary Perspective. [2022]Recent developments in prostate-specific membrane antigen (PSMA) targeted diagnostic imaging and therapeutics (theranostics) promise to advance the management of primary, biochemically recurrent, and metastatic prostate cancer. In order to maximize the clinical impact of PSMA-targeted theranostics, a coordinated approach between the clinical stakeholders involved in prostate cancer management is required. Here, we present a vision for multidisciplinary use of PSMA theranostics from the viewpoints of nuclear radiology, medical oncology, urology, and radiation oncology. We review the currently available and forthcoming PSMA-based imaging and therapeutics and examine current and potential impacts on prostate cancer management from early localized disease to advanced treatment-refractory disease. Finally, we highlight the clinical and research opportunities related to PSMA-targeted theranostics and describe the importance of multidisciplinary collaboration in this space.
Utility of PET to Appropriately Select Patients for PSMA-Targeted Theranostics. [2023]The majority of aggressive prostate cancers overexpress the transmembrane protein prostate-specific membrane antigen (PSMA). PSMA is, therefore, an attractive target for drug development. Over the last decade, numerous PSMA-targeted radiopharmaceuticals for imaging and therapy have been developed and investigated in theranostic combination. PSMA-targeted radiopharmaceuticals for imaging have been primarily developed for PET. PSMA PET provides whole-body evaluation of the degree of PSMA expression on tumors and potentially provides a method to better select patients for PSMA-targeted therapy. Numerous PSMA-targeted therapeutic agents using β- or α-particle emitters are under study in clinical trials. In particular, the β-particle-emitting radioisotope 177Lu bound to PSMA-targeted small molecules have ongoing and completed late-stage clinical trials in metastatic castration-resistant prostate cancer. To define the most appropriate patient group for PSMA-targeted therapeutics, multiple studies have investigated PSMA and FDG PET/CT to establish PET parameters as predictive and prognostic biomarkers. This article discusses recent clinical trials that examine the optimal use of PET for the selection of patients for PSMA-targeted therapeutics and provides an integrative overview of choice of PET tracer(s), targeting molecule, therapeutic radioisotope, nonradioactive therapy, and cancer type (prostate or nonprostate).
Image-Guided Surgery: Are We Getting the Most Out of Small-Molecule Prostate-Specific-Membrane-Antigen-Targeted Tracers? [2023]Expressed on virtually all prostate cancers and their metastases, the transmembrane protein prostate-specific membrane antigen (PSMA) provides a valuable target for the imaging of prostate cancer. Not only does PSMA provide a target for noninvasive diagnostic imaging, e.g., PSMA-positron emission tomography (PSMA-PET), it can also be used to guide surgical resections of PSMA-positive lesions. The latter characteristic has led to the development of a plethora of PSMA-targeted tracers, i.e., radiolabeled, fluorescent, or hybrid. With image-guided surgery applications in mind, this review discusses these compounds based on clinical need. Here, the focus is on the chemical aspects (e.g., imaging label, spacer moiety, and targeting vector) and their impact on in vitro and in vivo tracer characteristics (e.g., affinity, tumor uptake, and clearance pattern).
Phase I/IIa trial of 18F-prostate specific membrane antigen (PSMA) 1007 PET/CT in healthy volunteers and prostate cancer patients. [2023]18F-PSMA 1007 is a promising PET tracer for prostate cancer. We aimed to examine the safety, biodistribution, radiation dosimetry, and clinical effectiveness in Japanese healthy volunteers and patients with prostate cancer.
An Improved 211At-Labeled Agent for PSMA-Targeted α-Therapy. [2022]α-Particle emitters targeting the prostate-specific membrane antigen (PSMA) proved effective in treating patients with prostate cancer who were unresponsive to the corresponding β-particle therapy. 211At is an α-emitter that may engender less toxicity than other α-emitting agents. We synthesized a new 211At-labeled radiotracer targeting PSMA that resulted from the search for a pharmacokinetically optimized agent. Methods: A small series of 125I-labeled compounds was synthesized from tin precursors to evaluate the effect of the location of the radiohalogen within the molecule and the presence of lutetium in the chelate on biodistribution. On that basis, 211At-3-Lu was selected and evaluated in cell uptake and internalization studies, and biodistribution and PSMA-expressing (PSMA+) PC3 PIP tumor growth control were evaluated in experimental flank and metastatic (PC3-ML-Luc) models. A long-term (13-mo) toxicity study was performed for 211At-3-Lu, including tissue chemistries and histopathology. Results: The radiochemical yield of 211At-3-Lu was 17.8% ± 8.2%. Lead compound 211At-3-Lu demonstrated total uptake within PSMA+ PC3 PIP cells of 13.4 ± 0.5% of the input dose after 4 h of incubation, with little uptake in control cells. In SCID mice, 211At-3-Lu provided uptake that was 30.6 ± 4.8 percentage injected dose per gram (%ID/g) in PSMA+ PC3 PIP tumor at 1 h after injection, and this uptake decreased to 9.46 ± 0.96 %ID/g by 24 h. Tumor-to-salivary gland and tumor-to-kidney ratios were 129 ± 99 at 4 h and 130 ± 113 at 24 h, respectively. Deastatination was not significant (stomach, 0.34 ± 0.20 %ID/g at 4 h). Dose-dependent survival was demonstrated at higher doses (>1.48 MBq) in both flank and metastatic models. There was little off-target toxicity, as demonstrated by hematopoietic stability, unchanged tissue chemistries, weight gain rather than loss throughout treatment, and favorable histopathologic findings. Conclusion: Compound 211At-3-Lu or close analogs may provide limited and acceptable toxicity while retaining efficacy in management of prostate cancer.
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]Objectives: To assess the safety and clinical impact of a novel, kit-based formulation of 68Ga-THP PSMA positron emission tomography/computed tomography (PET/CT) when used to guide the management of patients with prostate cancer (PCa). Methods: Patients were prospectively recruited in to one of: Group A: high-risk untreated prostate cancer; Gleason score >4+3, or PSA >20 ng/mL or clinical stage >T2c. Group B: biochemical recurrence (BCR) and eligible for salvage treatment after radical prostatectomy with two consecutive rises in prostate specific antigen (PSA) with a three month interval in between reads and final PSA >0.1 ng/mL or a PSA level >0.5 ng/mL. Group C: BCR with radical curative radiotherapy or brachytherapy at least three months prior to enrolment, and an increase in PSA level >2.0 ng/mL above the nadir level after radiotherapy or brachytherapy. Patients underwent evaluation with PET/CT 60 minutes following intravenous administration of 160±30 MBq of 68Ga-THP PSMA. Safety was assessed by means including vital signs, cardiovascular profile, serum haematology, biochemistry, urinalysis, PSA, and Adverse Events (AEs). A change in management was reported when the predefined clinical management of the patient altered as a result of 68Ga-THP PSMA PET/CT findings. Results: Forty-nine patients were evaluated with PET/CT; 20 in Group A, 21 in Group B and 8 in Group C. No patients experienced serious AEs discontinued the study due to AEs, or died during the study. Two patients had Treatment Emergent AEs attributed to 68Ga-THP-PSMA (pruritus in one patient and intravenous catheter site rash in another). Management change secondary to PET/CT occurred in 42.9% of all patients; 30% in Group A, 42.9% in Group B and 75% in Group C. Conclusion: 68Ga-THP PSMA was safe to use with no serious AE and no AE resulting in withdrawal from the study. 68Ga-THP PSMA PET/CT changed the management of patients in 42.9% of the study population, comparable to studies using other PSMA tracers. These data form the basis of a planned Phase III study of 68Ga-THP PSMA in patients with prostate cancer.
Radiation Dosimetry of 99mTc-PSMA I&S: A Single-Center Prospective Study. [2022]99mTc-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. The primary aim of this study was to estimate the dosimetry of 99mTc-PSMA I&S using a hybrid method (sequential γ-planar imaging and 1 single SPECT/CT) in healthy volunteers. The secondary aim was to depict the tracer biodistribution and tumor-to-background ratios (TBRs) in patients with prostate cancer (PCa). Methods: Dosimetry of 99mTc-PSMA I&S was investigated in 4 healthy volunteers. Whole-body planar imaging was acquired at 1, 2, 3, 6, and 24 h and SPECT/CT at 6 h after tracer injection. Contours of organs were drawn on all acquisitions to determine organ activity at each time point. Absorbed dose was estimated using 2 methods: independent curve-fitting manual method (Levenberg-Marquardt-based algorithm using dose factors from RAdiation Dose Assessment Resource [RADAR] website) and OLINDA/EXM software (version 2.0; HERMES Medical Solutions). Biodistribution of 99mTc-PSMA I&S was assessed in 10 patients with PCa on SPECT/CT images at 6 h. Tumor uptake (SUVmax), and TBR (tumor SUVmax/background organ SUVmean) using muscle (T/M), bladder (T/B), and intestine (T/I) as background organs were determined. Results: The mean injected activity of 99mTc-PSMA I&S was 717 MBq (range: 562-828 MBq). No adverse events related to the injection of 99mTc-PSMA I&S were reported. The average radiation effective dose was 0.0055 mSv/MBq with the RADAR manual method and 0.0052 mSv/MBq with OLINDA/EXM. Total body effective dose ranged between 3.33-4.42 and 3.11-4.23 mSv, respectively. All PCa patients showed high tracer uptake in primary and metastatic lesions with T/M, T/B, and T/I ranging from 5.29-110, 0.11-7.02, and 0.96-16.30, respectively. Conclusion: Effective doses of 99mTc-PSMA I&S were comparable to those known for most of the 99mTc tracers and was lower than for the 68Ga-labeled and 18F-labeled agents. 99mTc-PSMA I&S SPECT/CT showed high TBR in PCa patients. This study can provide required data for translation and approval of 99mTc-PSMA I&S by regulatory agencies.
Dosimetry estimation and preliminary clinical application of [99mTc]Tc-HYNIC-PSMA-XL-2 in prostate cancer. [2023]Label="OBJECTIVE" NlmCategory="OBJECTIVE">Molecular imaging of prostate-specific membrane antigen (PSMA) inhibitors has become a favorite for prostate cancer (PCa). This study aimed to estimate the dosimetry and the preliminary clinical application of the [99mTc]Tc-HYNIC-PSMA-XL-2, which is a novel imaging tracer invented by our team that can specifically targets PSMA for PCa and its metastases.
Heterogeneity of prostate-specific membrane antigen (PSMA) and PSMA-ligand uptake detection combining autoradiography and postoperative pathology in primary prostate cancer. [2023]Label="BACKGROUND" NlmCategory="BACKGROUND">Targeting prostate-specific membrane antigen (PSMA) has been highly successful for imaging and treatment of prostate cancer. However, heterogeneity in immunohistochemistry indicates limitations in the effect of imaging and radionuclide therapy of multifocal disease. 99mTc-PSMA-I&S is a γ-emitting probe, which can be used for intraoperative lesion detection and postsurgical autoradiography (ARG). We aimed to study its intraprostatic distribution and compared it with (immuno)-histopathology.
Development of in-House Synthesis and Quality Control of [99mTc]Tc-PSMA-I&S. [2023]Many radioactive PSMA inhibitory substances have already been developed for PET diagnostics and therapy of prostate cancer. Because PET radionuclides and instrumentation may not be available, technetium-99 m labelled tracers can be considered as a diagnostic alternative. A suitable tracer is [99mTc]Tc-PSMA-I&S, primarily developed for radio-guided surgery, which has been identified for diagnostics of prostate cancer. However, there is no commercial kit approved for the preparation of [99mTc]Tc-PSMA-I&S on the market. This work presents an automated process for the synthesis of [99mTc]Tc-PSMA-I&S concerning good manufacturing practice (GMP). We used a Scintomics GRP 4 V module, with the SCC software package for programming sequences for this development. The optimum reaction conditions were evaluated in preliminary experiments. The pH of the reaction solution was found to be crucial for the radiochemical yield and radiochemical purity. The validation of [99mTc]Tc-PSMA-I&S (n = 3) achieved a stable radiochemical yield of 58.7 ± 1.5% and stable radiochemical purities of 93.0 ± 0.3%. The amount of free [99mTc]TcO4− in the solution and reduced hydrolysed [99mTc]TcO2 was