Head-to-head Comparison of 68Ga-PSMA-11 and 18F-PSMA-1007

Head-to-head Comparison of 68Ga-PSMA-11 and 18F-PSMA-1007 for the Detection of Recurrent Prostate Cancer in PSMA-ligand PET/CT

The aim of this study is to provide robust data on the head-to-head comparison of the two ligands of the prostate specific membrane antigen (PSMA) available in Switzerland for positron emission tomography (PET)-imaging, i.e. 68Ga-PSMA-11 und 18F-PSMA-1007.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Diagnostic test: 18F-PSMA-1007; Diagnostic test: 68Ga-PSMA-11

Detailed Description

Prostate Cancer (PC) is the most common malignancy in men and the second leading cause of cancer-related death in men. Despite initial therapy at early stage disease, biochemical recurrence remains a commonly encountered entity and presents a challenge for conventional imaging modalities given their limited abilities to detect disease at early stages of recurrence.

PET/CT with ligands of the prostate specific membrane antigen has been shown to have a significant impact on treatment and is now the sine qua non for staging of recurrent PC. For example, accurate identification of PC lesions allows for more accurate radiotherapy planning, allowing for an individualised treatment strategy. There is therefore a substantial clinical requirement for the accurate identification and stratification of individuals in whom prostate cancer is diagnosed and at earlier stages of recurrent disease when the chance of a curative treatment is at its highest.

It is in this context that PSMA has become the focus of much attention owing to its high levels of expression on PC cells and has rapidly established itself as the investigation of choice in recurrent PC. Furthermore, PSMA-directed radioligand therapy is a rapidly evolving treatment modality for metastatic disease, creating an additional therapeutic role for PSMA-ligand molecular imaging, for which the term "theragnostics" has been coined. The challenge for nuclear medicine is therefore to develop tracers and examination protocols that provide optimal detection and characterisation of disease, thus improving upon this promising technique.

There are currently no published prospective head-to-head studies comparing these two tracers in recurrent PC. Because of this lack of data, there are no clear recommendations about which tracer to use and in which situation.

This study aims to fill this gap and provide comprehensive data with the potential to improve the diagnosis of PC. By providing robust data comparing the two tracers, such data will also provide guidance to clinicians faced with the scenario of an initially negative 68Ga-PSMA-11 PET as to the diagnostic utility of an additional 18F-PSMA-1007 PET, or vice-versa, and in which scenarios repeated scanning may be justified.

Finally, the application of the radiotracer into the same patient allows for a comparison of tracer kinetics. Although radiotracer kinetics are well known from the original pioneering dosimetric publications, they have never been compared in a head to head fashion and not in biochemical recurrence. Obtaining dynamic scans over the first hour post injection will allow intra-individual dosimetry and a head-to-head comparison of parametric imaging parameters, allowing a direct comparison of the radiotracer's affinity using standard parametric imaging techniques.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital, Universitätsspital Bern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with known biochemical recurrence of a histologically confirmed prostate cancer post radical prostatectomy, defined as two consecutive prostate specific antigen (PSA) values > 0.2 ng/ml:
• Post prostatectomy: Patients > 18 y/o
• PSA measured within ± 4 weeks of the first PSMA-PET/CT
• Patients providing written informed consent
• No change in PC treatment in the period between the first and second scans

Exclusion Criteria:

• Patients receiving androgen deprivation therapy (ADT) within 6 months prior to the PSMA-PET/CT
• Patients with contraindication to diuresis with 20mg Furosemide
• Patients with renal dialysis or relevant renal impairment (eGFR < 35 ml/min)
• Inability to provide written informed consent
• Inability to schedule and attend two consecutive PET examinations
• Patients undergoing active treatment for a second non-prostatic malignancy at the time of the first scan.
• Known sensitivity or allergy to PSMA-ligands or one of the components of the radiotracer solutions used.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1; Patients receive first a PET/CT with 68Ga-PSMA-11 and a second PET/CT with 18F-PSMA-1007	Diagnostic test: 18F-PSMA-1007; PET/CT scan using 18F-PSMA-1007; Diagnostic test: 68Ga-PSMA-11; PET/CT scan using 68Ga-PSMA-11
Active Comparator: Arm 2; Patients receive first a PET/CT with 18F-PSMA-1007 and a second with 68Ga-PSMA-11	Diagnostic test: 18F-PSMA-1007; PET/CT scan using 18F-PSMA-1007; Diagnostic test: 68Ga-PSMA-11; PET/CT scan using 68Ga-PSMA-11

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-level detection rate	The primary endpoint is the proportion of patients with a pathological PSMA-positive finding (= patient-based sensitivity) at one time-point (2h) with the existing standard-of-care (68Ga-PSMA-11) compared to the new tracer (18F-PSMA-1007).	3-6 months following final scan

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of tracer kinetics	Intra-individual comparison of the parametric imaging parameter KD (measure of tracer affinity) for the two radiotracers.	For the first n=10 individuals, expected to be after 3 months
Per region-based detection rate	- The number of pathological, benign and uncertain lesions for each tracer in five regions (prostate bed, pelvic lymph nodes, extra-pelvic lymph nodes, bone, or other organs) classified by six blinded readers (three for each tracer) using previously published interpretation guidelines (PSMA-Rads 1.0)	Confirmed by 12 months' follow up from date of scan to a composite standard
Interreader reliability	Readers shall independently classify all PSMA-avid lesions according to previously published diagnostic criteria. The frequency of benign, equivocal and pathological lesions will be noted. Lesions will additionally be classified by region (prostate bed (T), pelvic lymph nodes (N), extrapelvic lymph nodes (M1a), bone (M1b) or other organs (M1c)). The interreader reliability for these classifications will be compared between all readers.	Within 3-6 months of last scan
Region based PPV	- The positive predictive value (PPV) stratified by region (local recurrence, lymph node, solid organ, bone) i.e. the percentage of pathological lesions that are confirmed pathological at the twelve months follow-up (based on the subset of patients and lesions with follow-up data at twelve months).	12 months from the last scan
Lesion semiquantitative radiotracer uptake	- semiquantitative radiotracer uptake will be assessed by standardised uptake values (SUV) as well as tumour to background contrast in a lesion based analysis. The tumour to background ratio (TBR) is defined as lesion SUV ÷ SUV of reference background region, where the background uptake is defined by convention as the left gluteal musculature	Within 6 months of scan date
Number of patients with adverse events and their severity	- Number and severity of adverse events per tracer (up to 48 hours follow up).	48 hours
Lesion based PPV	In a second round of tumour classification, two readers (in consensus) will classify each lesion as pathological, benign or uncertain in a lesion-specific approach and perform a lesion based follow-up to assess PPV on the lesion level.	12 months from the last scan

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Study Chair: Axel Rominger, MD, Inselspital

Publications and helpful links

General Publications

• Alberts I, Butikofer L, Rominger A, Afshar-Oromieh A. A randomised, prospective and head-to-head comparison of [68Ga]Ga-PSMA-11 and [18F]PSMA-1007 for the detection of recurrent prostate cancer in PSMA-ligand PET/CT-Protocol design and rationale. PLoS One. 2022 Jul 19;17(7):e0270269. doi: 10.1371/journal.pone.0270269. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2022
• Primary Completion (Actual): May 1, 2024
• Study Completion (Actual): October 30, 2024

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: October 14, 2021
• First Posted (Actual): October 15, 2021

Study Record Updates

• Last Update Posted (Estimated): December 10, 2024
• Last Update Submitted That Met QC Criteria: December 9, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: recurrent prostate cancer; PET/CT; PSMA; 68Ga-PSMA-11; 18F-PSMA-1007
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Gallium 68 PSMA-11
• Other Study ID Numbers: 2020-02903

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data available upon reasonable request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No