Effects of Direct Artery Injection on Prostate Cancer Drug Delivery and Tumor Uptake: Imaging-Based Prediction of Treatment Effectiveness

Official title

Impact of Intra-Arterial PSMA Injection on Distribution and Tumor Uptake: Texture Analysis and Dose Radicality Prediction in Prostate Cancer

Overview

The goal of this clinical trial is to learn whether intra-arterial (IA) administration of 68Ga-PSMA improves tumor uptake and distribution compared with standard intravenous (IV) administration in patients with localized high-risk prostate cancer. The study will also evaluate the safety of the IA procedure and investigate whether advanced PET/CT imaging features can help predict the radiation dose needed for future personalized 177Lu-PSMA radioligand therapy. The main questions it aims to answer are: * Does intra-arterial 68Ga-PSMA administration result in higher and more homogeneous tumor uptake than standard intravenous administration? * Can PET/CT texture analysis and dosimetric modeling predict the radiation dose required to achieve a curative effect with 177Lu-PSMA therapy? * What radiation exposure and procedure-related risks are associated with intra-arterial administration for patients and medical staff? Researchers will compare PSMA uptake and distribution after intravenous and intra-arterial administration of 68Ga-PSMA using PET/CT imaging. Participants will: * Undergo a standard intravenous 68Ga-PSMA PET/CT scan. * Undergo a second 68Ga-PSMA PET/CT scan following selective intra-arterial administration through the prostatic artery. * Have imaging data analyzed using advanced texture analysis and voxel-based dosimetry methods. * Undergo radical prostatectomy according to standard clinical care, with pathological analysis of surgical specimens. * Be monitored for adverse events, radiation exposure, and procedural safety throughout the study.

Detailed description

PSMA-targeted radioligands have become an important tool for imaging and treatment of prostate cancer. Intravenous (IV) administration is the current standard route of administration; however, intra-arterial (IA) delivery through the prostatic artery may increase local radioligand concentration within the tumor while reducing systemic distribution.

This prospective, single-center, interventional study aims to evaluate the effect of IA administration of 68Ga-PSMA on tracer distribution and tumor uptake in patients with localized high-risk prostate cancer undergoing radical prostatectomy.

Participants will undergo standard-of-care 68Ga-PSMA PET/CT imaging following intravenous administration and a second PET/CT examination following selective intra-arterial administration of 68Ga-PSMA through the prostatic artery. Quantitative PET/CT analysis will be used to compare tumor uptake, tumor-to-background ratios, and intratumoral distribution between the two administration routes.

The study will also establish and evaluate a standardized technique for selective prostatic artery catheterization and IA radioligand administration. Procedural feasibility, technical success, adverse events, and radiation exposure to patients and medical personnel will be assessed.

Advanced radiomic texture analysis and voxel-based dosimetry will be performed on PET/CT datasets to characterize intratumoral heterogeneity and investigate imaging biomarkers associated with radiotracer distribution. These data will be used to develop predictive models estimating the radiation dose required to achieve a curative ("radical") effect with future 177Lu-PSMA radioligand therapy.

Following imaging, participants will undergo radical prostatectomy according to standard clinical practice. Histopathological findings will be correlated with imaging-derived uptake and texture parameters.

The study is designed to determine whether IA administration improves PSMA uptake and distribution compared with IV administration and to explore imaging-based approaches for personalized radioligand therapy planning in localized prostate cancer.

Interventions

• Procedure Intraarterial injection of 68Ga-PSMA
  Additional intervention to the standard of care for prostate cancer treatment - prostate artery catheterization and intra-arterial injection of 68Ga-PSMA with subsequent PET/CT scan.

Primary outcome measures

• Relative increase in intratumoral PSMA uptake after intra-arterial versus intravenous ⁶⁸Ga-PSMA administration [Time frame: Up to 6 weeks from enrollment.]

Secondary outcome measures (5)

• Technical success rate of selective intra-arterial prostate artery catheterization [Time frame: Up to 6 weeks from enrollment.]
• Procedural safety of intra-arterial PSMA administration [Time frame: From IA administration until radical prostatectomy at up to 3 months from enrollment.]
• Patient and operator radiation exposure during intra-arterial versus intravenous procedures [Time frame: Up to 6 weeks from enrollment.]
• Identification of PET texture biomarkers associated with optimal tumor saturation [Time frame: Up to 1 year from enrollment.]
• Predicted absorbed tumor dose achievable with ¹⁷⁷Lu-PSMA therapy [Time frame: Up to 1 year from enrollment.]

Eligibility criteria

Inclusion criteria

• Adult male patients with biopsy-proven prostate adenocarcinoma up to stages ≤T3bN1 by initial preoperative examination, with no distant metastases (M0) on ⁶⁸Ga-PSMA PET/CT.
• Systemic therapy-naive patients scheduled for radical prostatectomy with/without pelvic lymph node dissection with curative intent.
• High-risk localized or locally-advanced prostate cancer according to European Association of Urology criteria, including one of the following:

• Prostate-specific antigen > 20ng/mL2 or ISUP grade 4/5.
• Clinical T stage cT3-4\* and/or N1 disease (involvement of lymph nodes at or below the bifurcation of the common iliac arteries), any ISUP grade, and any
• High PSMA avidity on ⁶⁸Ga-PSMA PET/CT, defined as SUVmax ≥20.
• Normal baseline hematological function.
• Normal serum biochemistry.
• Signed informed consent form.

Exclusion criteria

• Patients with other (non-adenocarcinoma) biopsy-proven histology of prostate cancer.
• Patients with low-risk prostate cancer according to European Association of Urology criteria, including any of the following:

• Prostate-specific antigen <10 ng/ml.
• International Society of Urological Pathology grade group 1.
• Clinical T stage T1-T2a digital rectal examination.
• Prior radiotherapy or systemic therapy for prostate cancer.
• Prostate cancer with low PSMA avidity (SUVmax <20) on ⁶⁸Ga-PSMA PET/CT.
• Evidence of distant metastatic spread (M1) on ⁶⁸Ga-PSMA PET/CT.
• Contraindications for radical prostatectomy.
• Major comorbidities and laboratory abnormalities that might confound the results of the trial or interfere with the patient's ability to participate.
• Refusal to participate in the trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

Lithuania · 1 center

• Lithuanian University of Health Sciences Kaunas Clinics — Kaunas

Identifiers

NCT: NCT07656337 · PSMA 1.0

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗