PSA-stratified detection rates for [68Ga]THP-PSMA, a novel probe for rapid kit-based 68Ga-labeling and PET imaging, in patients with biochemical recurrence after primary therapy for prostate cancer.

PURPOSE: [68Ga]Tris(hydroxypyridinone)(THP)-PSMA is a novel radiopharmaceutical for one-step kit-based radiolabelling, based on direct chelation of 68Ga3+ at low concentration, room temperature and over a wide pH range, using direct elution from a 68Ge/68Ga-generator. We evaluated the clinical detection rates of [68Ga]THP-PSMA PET/CT in patients with biochemically recurrent prostate cancer after prostatectomy. METHODS: Consecutive patients (n=99) referred for evaluation of biochemical relapse of prostate cancer by [68Ga]THP-PSMA PET/CT were analyzed retrospectively. Patients underwent a standard whole-body PET/CT (1 h p.i.), followed by delayed (3 h p.i.) imaging of the abdomen. PSA-stratified cohorts of positive PET/CT results, standardized uptake values (SUVs) and target-to-background ratios (TBRs) were analyzed, and compared between standard and delayed imaging. RESULTS: At least one lesion suggestive of recurrent or metastatic prostate cancer was identified on PET images in 52 patients (52.5%). Detection rates of [68Ga]THP-PSMA PET/CT increased with increasing PSA level: 94.1% for a PSA value of ≥10 ng/mL, 77.3% for a PSA value of 2 to <10 ng/mL, 54.5% for a PSA value of 1 to <2 ng/mL, 14.3% for a PSA value of 0.5 to <1 ng/mL, 20.0% for a PSA value of >0.2 to <0.5, and 22.2% for a PSA value of 0.01 to 0.2 ng/mL. [68Ga]THP-PSMA uptake (SUVs) in metastases decreased over time, whereas TBRs improved. Delayed imaging at 3 h p.i. exclusively identified pathologic findings in 2% of [68Ga]THP-PSMA PET/CT scans. Detection rate was higher in patients with a Gleason score ≥8 (P=0.02) and in patients receiving androgen deprivation therapy (P=0.003). CONCLUSIONS: In this study, [68Ga]THP-PSMA PET/CT showed suitable detection rates in patients with biochemical recurrence of prostate cancer and PSA levels ≥ 2 ng /mL. Detections rates were lower than in previous studies evaluating other PSMA ligands, though prospective direct radiotracer comparison studies are mandatory particularly in patients with low PSA levels to evaluate the relative performance of different PSMA ligands.

Imaging Characteristics and First Experience of [68Ga]THP-PSMA, a Novel Probe for Rapid Kit-Based Ga-68 Labeling and PET Imaging: Comparative Analysis with [68Ga]PSMA I&T.

PURPOSE: [68Ga]Trishydroxypyridinone (THP)-prostate-specific membrane antigen (PSMA) is a novel tracer that can be labeled in one step by cold reconstitution of a kit with unprocessed generator eluate, targeting PSMA via the lysine-urea-glutamate (KuE) motif. The aim of this study was to evaluate the human imaging characteristics of [68Ga]THP-PSMA. PROCEDURES: [68Ga]THP-PSMA positron emission tomography (PET)/x-ray computed tomography (CT) was performed in 25 patients with biochemical recurrence after radical prostatectomy for prostate cancer. Urinary and biliary excretion and tumor lesion uptake were quantified using standardized uptake values (SUVs). Imaging characteristics were assessed in terms of non-target organ uptake, background activity, target-to-background ratios (TBRs) of tumor lesions, and frequency of bladder halo artifacts. Findings were compared to a matched cohort of 25 patients undergoing PET/CT with the established agent [68Ga]PSMA I&T. RESULTS: Physiologic uptake of [68Ga]THP-PSMA was significantly lower in salivary glands (P < 0.0001), liver (P < 0.0001), spleen (P < 0.0001), and kidneys (P < 0.0001) than with [68Ga]PSMA I&T. While biliary tracer excretion of [68Ga]THP-PSMA was negligible, urinary tracer excretion of [68Ga]THP-PSMA was fast, and significantly higher than for [68Ga]PSMA I&T, contributing to a higher frequency of bladder artifacts. Malignant lesion uptake of [68Ga]THP-PSMA assessed as either SUV or TBR was significantly lower than with [68Ga]PSMA I&T. CONCLUSION: [68Ga]THP-PSMA yields suitable in vivo uptake characteristics. The simplified synthesis method for [68Ga]THP-PSMA may facilitate wider application and higher patient throughput with PSMA imaging. However, direct intraindividual comparison studies are needed to assess the relative performance of [68Ga]THP-PSMA vs other PSMA ligands in terms of clinical detection rate and image quality.

Multimodality imaging of blood-brain barrier impairment during epileptogenesis.

Insult-associated blood-brain barrier leakage is strongly suggested to be a key step during epileptogenesis. In this study, we used three non-invasive translational imaging modalities, i.e. positron emission tomography, single photon emission computed tomography, and magnetic resonance imaging, to evaluate BBB leakage after an epileptogenic brain insult. Sprague-Dawley rats were scanned during early epileptogenesis initiated by status epilepticus. Positron emission tomography and single photon emission computed tomography scans were performed using the novel tracer [68Ga]DTPA or [99mTc]DTPA, respectively. Magnetic resonance imaging included T2 and post-contrast T1 sequence after infusion of Gd-DTPA, gadobutrol, or Gd-albumin. All modalities revealed increased blood-brain barrier permeability 48 h post status epilepticus, mainly in epileptogenesis-associated brain regions like hippocampus, piriform cortex, thalamus, or amygdala. In hippocampus, Gd-DTPA-enhanced T1 magnetic resonance imaging signal was increased by 199%, [68Ga]DTPA positron emission tomography by 37%, and [99mTc]DTPA single photon emission computed tomography by 56%. Imaging results were substantiated by histological detection of albumin extravasation. Comparison with quantitative positron emission tomography and single photon emission computed tomography shows that magnetic resonance imaging sequences successfully amplify the signal from a moderate amount of extravasated DTPA molecules, enabling sensitive detection of blood-brain barrier disturbance in epileptogenesis. Imaging of the disturbed blood-brain barrier will give further pathophysiologic insights, will help to stratify anti-epileptogenic treatment targeting blood-brain barrier integrity, and may serve as a prognostic biomarker.