New Clinical Indications for 18F/11C-choline, New Tracers for Positron Emission Tomography and a Promising Hybrid Device for Prostate Cancer Staging: A Systematic Review of the Literature☆
Radiolabelled choline positron emission tomography has changed the management of prostate cancer patients. However, new emerging radiopharmaceutical agents, like radiolabelled prostate specific membrane antigen, and new promising hybrid imaging will begin new challenges in the diagnostic field.
Objective
The continuous evolution in nuclear medicine has led to the improvement in the detection of recurrent prostate cancer (PCa), particularly distant metastases. New horizons have been opened for radiolabelled choline positron emission tomography (PET)/computed tomography (CT) as a guide for salvage therapy or for the assessment of systemic therapies. In addition, new tracers and imaging tools have been recently tested, providing important information for the management of PCa patients. Herein we discuss: (1) the available evidence in literature on radiolabelled choline PET and their recent indications, (2) the role of alternative radiopharmaceutical agents, and (3) the advantages of a recent hybrid imaging device (PET/magnetic resonance imaging) in PCa.
Evidence acquisition
Data from recently published (2010–2015), original articles concerning the role of choline PET/CT, new emerging radiotracers, and a new imaging device are analysed. This review is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
Evidence synthesis
In the restaging phase, the detection rate of choline PET varies between 4% and 97%, mainly depending on the site of recurrence and prostate-specific antigen levels. Both 68gallium (68Ga)-prostate specific membrane antigen and 18F-fluciclovine are shown to be more accurate in the detection of recurrent disease as compared with radiolabelled choline PET/CT. Particularly, Ga68-PSMA has a detection rate of 50% and 68%, respectively for prostate-specific antigen levels < 0.5 ng/ml and 0.5–2 ng/ml. Moreover, 68Ga- PSMA PET/magnetic resonance imaging demonstrated a particularly higher accuracy in detecting PCa than PET/CT. New tracers, such as radiolabelled bombesin or urokinase-type plasminogen activator receptor, are promising, but few data in clinical practice are available today.
Conclusions
Some limitations emerge from the published papers, both for radiolabelled choline PET/CT and also for new radiopharmaceutical agents. Efforts are still needed to enhance the impact of published data in the world of oncology, in particular when new radiopharmaceuticals are introduced into the clinical arena.
Patient summary
In the present review, the authors summarise the last evidences in clinical practice for the assessment of prostate cancer, by using nuclear medicine modalities, like positron emission tomography/computed tomography and positron emission tomography/magnetic resonance imaging.
Introduction
Prostate cancer (PCa) is the most common malignancy in elderly men and a common cause of death in Europe and USA [1]. Recent developments in imaging modalities have provided new useful information in the management of patients with PCa. For example, the early identification of local or distant recurrence of disease can be a useful guide for appropriate therapy.
Clinical indications for the use of imaging in PCa depend on the different phases of the disease and can be summarised as follows: initial assessment of disease (limited or extended cancer), re-assessment after primary treatment or in case of biochemical recurrence, progression of disease, and appearance of hormone-resistant phenotype. Each setting can be linked to different imaging modalities in accordance with the clinical question: the definition of widespread disease, guidance for salvage treatments, and the assessment of treatment efficacy. Magnetic resonance imaging (MRI) and positron emission tomography (PET) with radiopharmaceutical agents showing a tropism for PCa cells have been introduced into clinical guidelines [2], [3] and into current clinical routines [4], particularly for the restaging of patients with a suspicion of recurrent disease. The majority of reviews and original articles are mainly focused on radiolabelled choline PET/CT, which has known limitations related to physiological biodistribution and diagnostic performances in some settings of the disease. Innovative PET tracers have thus been proposed to overcome these limitations. With this vision, we reviewed the current clinical impact of radiolabelled choline PET in PCa management and its recent indications. Moreover, we considered the role of alternative radiopharmaceuticals as diagnostic agents, in particular radiolabelled prostate specific membrane antigen (PSMA) and 18F-fluciclovine (FACBC), and the advantages of the new hybrid imaging device, PET/MRI. Furthermore, we provide additional information on “new emerging” tracers, in particular, 18F-bombesin and radiolabelled urokinase-type plasminogen activator receptor (uPAR), which might improve the detection of PCa and guide clinicians in the use of targeted therapies.
Section snippets
Literature search and inclusion criteria
We performed a comprehensive literature search in the electronic databases Pubmed, Web of Science, and Cochrane Library; we found approximately 1000 articles published in the 5-yr period 2010–2015 containing the keywords “PET” and “choline” or “PET” and “prostate cancer”. All available abstracts were reviewed by the authors, and the most pertinent full articles were examined in detail. Inclusion criteria were: (1) English language, (2) more than 10 enrolled patients, (3) clearly presented and
Radiotherapy planning and salvage RP
Salvage RT to the prostatic fossa is the only treatment option with curative intent for patients who experience a biochemical relapse after RP. If evidence of local recurrence is present, the salvage radiation dose applied to the prostate bed is increased and when evidence of pelvic lymph node metastases is present, irradiation of pelvic lymph nodes with a boost to the suspicious lymph nodes can be considered. The additive information expected from a diagnostic modality in order to increase the
Alternative PET tracers
In accordance with the abovementioned limitations, new alternative tracers have been proposed for the assessment of PCa, for both the initial staging of disease and the detection of disease recurrences. Below, we discuss new experimental radiopharmaceutical agents that have shown different advantages, particularly in terms of detection rate.
PET/MRI
Simultaneous PET/MRI is a recently developed technology that is expected to be a better diagnostic imaging modality than the two modalities separately, because it combines functional, molecular, and morphological information. Moreover, the advantages of PET/MRI include less exposure to radiation for the patient and a better soft tissue contrast resolution. Recently, Kim et al [70] demonstrated that simultaneous PET/MRI is better for the detection of PCa than the individual modalities separately
Discussion and conclusion
The recent introduction of radiolabelled PSMA agents has raised some questions on the utility of radiolabelled choline compounds. However, some common limitations emerged from the published papers for both tracers. In most cases, no objective evaluation of true positive or true negative results is possible. Moreover, a clear standardisation for patient preparation or image acquisition is currently not available. Unfortunately, to date, it is impossible to find a balance between “old” and “new”
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2023, Journal of the American College of Radiology
Prostate cancer has a wide spectrum ranging between low-grade localized disease and castrate-resistant metastatic disease. Although whole gland and systematic therapies result in cure in the majority of patients, recurrent and metastatic prostate cancer can still occur. Imaging approaches including anatomic, functional, and molecular modalities are continuously expanding. Currently, recurrent and metastatic prostate cancer is grouped in three major categories: 1) Clinical concern for residual or recurrent disease after radical prostatectomy, 2) Clinical concern for residual or recurrent disease after nonsurgical local and pelvic treatments, and 3) Metastatic prostate cancer treated by systemic therapy (androgen deprivation therapy, chemotherapy, immunotherapy). This document is a review of the current literature regarding imaging in these settings and the resulting recommendations for imaging. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
18F-fluorocholine positron emission tomography/CT (FCH PET/CT) and, more recently, 68Ga prostate-specific membrane antigen ligand PET/CT (PSMA PET/CT) are increasingly being performed to stage patients with BF after curative treatment for localized prostate cancer. They have better sensitivity and specificity than conventional imaging and make it possible to identify recurrence sites with accuracy at an earlier stage.9-12 The earlier detection of nodal and metastatic relapses, potentially making patients eligible for local salvage treatment, has led to a growing interest to treat these patients with curative intent.
The optimal salvage pelvic treatment for nodal recurrences in prostate cancer is not yet clearly defined. We aimed to compare outcomes of salvage involved-field radiation therapy (s-IFRT) and salvage extended-field radiation therapy (s-EFRT) for positron emission tomography/computed tomography–positive nodal-recurrent prostate cancer and to analyze patterns of progressions after salvage nodal radiation therapy.
Patients with 18F-fluorocholine or 68Ga prostate-specific membrane antigen ligand positron emission tomography/computed tomography–positive nodal-recurrent prostate cancer and treated with s-IFRT or s-EFRT were retrospectively selected. Time to biochemical failure, time to palliative androgen deprivation therapy (ADT), and distant metastasis–free survival were analyzed.
Between 2009 and 2019, 86 patients were treated with salvage nodal radiation therapy: 38 with s-IFRT and 48 with s-EFRT. After a median follow-up of 41.9 months (5.4-122.1 months), 47 patients presented a further relapse: 31 after s-IFRT and 16 after s-EFRT, with only 1 in-field relapse. The median time to palliative ADT was 24.8 months (95% confidence interval [CI], 13.3-93.5 months) in the s-IFRT group and not yet reached (95% CI, 40.3 months to not yet reached) in the s-EFRT group (P = .010). The 3-year biochemical failure–free rate was 70.2% (95% CI, 51.5%-82.9%) with s-IFRT and 73.9% (95% CI, 55.4%-85.7%) with s-EFRT (P = .657). The 3-year distant metastasis–free survival was 74.1% (95% CI, 56.0%-85.7%) with s-IFRT and 82.0% (95% CI, 63.0%-91.8%) with s-EFRT (P = .338).
s-EFRT and s-IFRT for positron emission tomography–positive nodal-recurrent prostate cancer provide excellent local control. Time to palliative ADT was longer following s-EFRT than following s-IFRT.
El concepto de medicina personalizada actualmente es de uso habitual en el ámbito de la medicina, incluyendo la medicina nuclear, en la que se utilizan radiotrazadores que se fijan a blancos moleculares específicos según la clínica o patología del paciente. La obtención de imágenes que confirman la fijación de un trazador en un tejido tumoral en forma específica abre la posibilidad de utilizar ese mismo trazador para fines terapéuticos. Lo anterior se logra al reemplazar el isótopo radioactivo por uno de mayor capacidad ionizante efectuando radioterapia dirigida molecularmente. Este concepto de teranóstica (terapia y diagnóstico) se utiliza en distintas condiciones en las cuales la medicina nuclear con moléculas radiomarcadas juega un rol destacado. El presente artículo tiene como objetivo revisar estas condiciones: patología tiroidea con yodo; tumores neuroendocrinos con análogos de somatostatina y cáncer de próstata con antígeno prostático específico de membrana (PSMA).
Tailored medicine is a customary concept in current medical practice, including nuclear medicine, which uses radiotracers that bind to specific molecular targets according to a patient's clinical situation or pathology. Once molecular images confirm high tumoral uptake of a specific radiotracer, a therapeutic option becomes available by replacing the radioactive isotope for another radioactive molecule, with higher ionizing capacity. This allows molecular guided radiotherapy, also known as theranostics (therapy and diagnostic), to be used in different pathologies where nuclear medicine plays an important role. The aim of this review will be to explore the following conditions: thyroid diseases and radioiodine; neuroendocrine tumors and radiolabeled somatostatin analogues; and prostatic cancer and radiolabeled prostatic specific membrane antigen (PSMA).
