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

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.

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.