Prostate-specific membrane antigen (PSMA)-ligand PET imaging provides unprecedented accuracy for whole-body staging of prostate cancer. As PSMA-ligand PET/CT is increasingly adopted in clinical ...trials and routine practice worldwide, a unified language for image reporting is urgently needed. We propose a molecular imaging TNM system (miTNM, version 1.0) as a standardized reporting framework for PSMA-ligand PET/CT or PET/MRI. miTNM is designed to organize findings in comprehensible categories to promote the exchange of information among physicians and institutions. Additionally, flowcharts integrating findings of PSMA-ligand PET and morphologic imaging have been designed to guide image interpretation. Specific applications, such as assessment of prognosis or impact on management, should be evaluated in future trials. miTNM is a living framework that evolves with clinical experience and scientific data.
Gallium 68 (
Ga)-labeled fibroblast activation protein (FAP) inhibitor (FAPI) PET is based on the molecular targeting of the FAP, which is known to be highly expressed in the major cell population in ...tumor stroma, termed cancer-associated fibroblasts. Among many FAP-targeted radiopharmaceuticals developed so far,
Ga-FAPI exhibits rapid tracer accumulation in target lesions and low background signal, which results in excellent imaging features. FAPI PET can be integrated in the clinical workflow and enables the detection of small primary or metastatic lesions, especially in the brain, liver, pancreas, and gastrointestinal tract due to the low tracer accumulation in these organs. Moreover, the DOTA (1,4,7,10-tetraazacylclododecane-1,4,7,10-tetrayl tetraacetic acid) chelator in the molecular structure allows coupling of the FAPI molecules with therapeutic emitters such as yttrium 90 for theranostic applications. This review provides an overview of the state of the art in FAP imaging, summarizes the current knowledge of relevant cancer biology, and highlights the latest findings in the clinical use of
Ga-FAPI PET and other current FAPI tracers. Published under a CC BY 4.0 license.
The prostate-specific membrane antigen (PSMA) has received increased consideration during the past few years as an excellent target for both imaging and therapy of prostate cancer. After many years ...of outstanding preclinical research, the first significant step forward in clinical use was achieved in 2008 with the first human experience with the small-molecule PSMA inhibitors
I-MIP-1972 and
I-MIP-1095. A clinical breakthrough followed in 2011 with
Ga-PSMA-11 for PET imaging and
I-MIP-1095 for endoradiotherapy of metastatic prostate cancer. Since then, PET/CT with
Ga-PSMA-11 has rapidly spread worldwide, and endoradiotherapy with PSMA ligands has been conducted at increasing numbers of centers.
Ga-PSMA-11 is currently the subject of multicenter studies in different countries. Since 2013,
I-related PSMA therapy has been replaced by
Lu-labeled ligands, such as PSMA-617, which is also the subject of multicenter studies. Alternative PSMA ligands for both imaging and therapy are available. Among them is
Tc-MIP-1404, which has recently entered a phase 3 clinical trial. This article focuses on the highlights of the development and clinical application of PSMA ligands.
Radionuclide Therapy of Metastatic Prostate Cancer Kratochwil, Clemens; Haberkorn, Uwe; Giesel, Frederik L.
Seminars in nuclear medicine,
July 2019, 2019-07-00, 20190701, Letnik:
49, Številka:
4
Journal Article
Recenzirano
The current mainstay of treatment in metastatic prostate cancer is based on hormonal manipulations. Standard androgen deprivation therapy and novel androgen axis drugs are commonly well tolerable and ...can stabilize metastatic hormone-sensitive prostate cancers for years. However, metastatic castration-resistant prostate cancer is still challenging to treat. Except taxanes, prostate cancer presents intrinsic resistance against conventional chemotherapies. The typically elderly patient population excludes more aggressive treatment regimens. First clinical trials evaluating immunotherapy or tyrosine-kinase-inhibitors against prostate cancer failed. In contrast, prostate cancer can be radiosensitive and external beam radiotherapy is effective in localized prostate cancer, thus providing a good rationale for the use of systemic radiopharmaceuticals in the metastatic setting. Beta-particle emitting “bone-seekers” have a long history and are effective as analgesics but do not improve survival because they are limited by red-marrow dose. Alpha emitting 223Radium can be used in a dose that prolongs survival but is restricted to bone-confined patients. Currently radiolabeled high-affinity ligands to the prostate-specific membrane antigen are in clinical evaluation. While radioimmunotherapy approaches were limited by the long circulation time and slow tumor-accumulation of antibodies, low molecular weight PSMA-specific ligands offer an approx. ten-fold improved tumor to red-marrow ratio in comparison to the unspecific bone-seekers. Early clinical studies demonstrate that regarding surrogate markers, such as >50% PSA reduction (60%) and radiologic response (80%), PSMA-therapy exceeds the antitumor activity of all approved or other recently tested compounds; for example, PSA-response was only observed in approx. a total of 10% of patients treated with ipilimumab, sunitinib, cabozantinib, or xofigo, respectively and in approx. 30, 40, 50% of patients treated with abiraterone, cabazitaxel, or enzalutamide. Also progression free and overall survivals of these single-arm studies appear promising when compared to historical controls. Consecutively, the first PSMA-RLT recently advanced into phase-3 (177Lu-PSMA-617; VISION-trial). Future developments aim to avoid off-target radiation by ligand-optimization and to outperform the antitumor activity of beta-emitter PSMA-RLT by labeling with highly focused, high energy transferring alpha-nuclides; however the latter potentially also increasing the risk of side-effects and additional early phase studies are needed to improve treatment protocols. Academically clinical research is developing prognostic tools to improve treatment benefit by selecting the most appropriate patients in advance.
Interstitial lung diseases (ILDs) comprise over 200 parenchymal lung disorders. Among them, fibrosing ILDs, especially idiopathic pulmonary fibrosis, are associated with a poor prognosis, whereas ...some other ILDs, such as sarcoidosis, have a much better prognosis. A high proportion manifests as fibrotic ILD (fILD). Lung cancer (LC) is a frequent complication of fILD. Activated fibroblasts are crucial for fibrotic processes in fILD. The aim of this exploratory study was to evaluate the imaging properties of static and dynamic fibroblast activation protein (FAP) inhibitor (FAPI) PET/CT in various types of fILD and to confirm FAP expression in fILD lesions by FAP immunohistochemistry of human fILD biopsy samples and of lung sections of genetically engineered (
) mice with an idiopathic pulmonary fibrosislike lung disease.
PET scans of 15 patients with fILD and suspected LC were acquired 10, 60, and 180 min after the administration of 150-250 MBq of a
Ga-labeled FAPI tracer (FAPI-46). In 3 patients, dynamic scans over 40 min were performed instead of imaging after 10 min. The SUV
and SUV
of fibrotic lesions and LC were measured and CT-density-corrected. Target-to-background ratios (TBRs) were calculated. PET imaging was correlated with CT-based fibrosis scores. Time-activity curves derived from dynamic imaging were analyzed. FAP immunohistochemistry of 4 human fILD biopsy samples and of fibrotic lungs of
mice was performed.
fILD lesions as well as LC showed markedly elevated
Ga-FAPI uptake (density-corrected SUV
and SUV
60 min after injection: 11.12 ± 6.71 and 4.29 ± 1.61, respectively, for fILD lesions and 16.69 ± 9.35 and 6.44 ± 3.29, respectively, for LC) and high TBR (TBR of density-corrected SUV
and SUV
60 min after injection: 2.30 ± 1.47 and 1.67 ± 0.79, respectively, for fILD and 3.90 ± 2.36 and 2.37 ± 1.14, respectively, for LC). SUV
and SUV
decreased over time, with a stable TBR for fILD and a trend toward an increasing TBR in LC. Dynamic imaging showed differing time-activity curves for fILD and LC.
Ga-FAPI uptake showed a positive correlation with the CT-based fibrosis index. Immunohistochemistry of human biopsy samples and the lungs of
mice showed a patchy expression of FAP in fibrotic lesions, preferentially in the transition zone to healthy lung parenchyma.
Ga-FAPI PET/CT imaging is a promising new imaging modality for fILD and LC. Its potential clinical value for monitoring and therapy evaluation of fILD should be investigated in future studies.
PET imaging with the prostate-specific membrane antigen (PSMA)-targeted radioligand (68)Ga-PSMA-11 is regarded as a significant step forward in the diagnosis of prostate cancer (PCa). More recently, ...a PSMA ligand was developed that can be labeled with (68)Ga, (111)In, (177)Lu, and (90)Y. This ligand, named PSMA-617, therefore enables both diagnosis and therapy of PCa. The aims of this evaluation were to clinically investigate the distribution of (68)Ga-PSMA-617 in normal tissues and in PCa lesions as well as to evaluate the radiation exposure by the radioligand in PET imaging.
Nineteen patients, most of them with recurrent PCa, were referred for (68)Ga-PSMA-617 PET/CT. The quantitative assessment of tracer uptake of several organs and of 53 representative tumor lesions was performed in 15 patients at 1 and 3 h after injection. In 4 additional patients, the same procedure was conducted at 5 min, 1 h, 2 h, 3 h, 4 h, and 5 h after injection. On the basis of the data for these 4 patients (mean injected dose, 231 MBq), the radiation exposure of a (68)Ga-PSMA-617 PET/CT was identified.
Intense tracer uptake was observed in the kidneys and salivary glands. In 14 of 19 patients (73.7%), at least 1 lesion suspected of being a tumor was detected at 3 h after injection. Of 53 representative tumor lesions selected at 3 h after injection, 47 lesions were visible at 1 h after injection. The mean tumor-to-background ratio for maximum standardized uptake value was 20.4 ± 17.3 (range, 2.3-84.0) at 1 h after injection and 38.2 ± 38.6 (range, 3.6-154.3) at 3 h after injection. The average radiation exposure (effective dose) was approximately 0.021 mSv/MBq.
Within healthy organs, the kidneys and salivary glands showed the highest (68)Ga-PSMA-617 uptake. The radiation exposure was relatively low. (68)Ga-PSMA-617 shows PCa lesions with high contrast. Images obtained between 2 and 3 h after injection seem to be the best option with regard to radiotracer uptake and tumor contrast. Later images can help to clarify unclear lesions.
Radiotherapy is the main therapeutic approach besides surgery of localized prostate cancer. It relies on risk stratification and exact staging. This report analyses the potential of ...(68)GaGlu-urea-Lys(Ahx)-HBED-CC ((68)Ga-PSMA-11), a new positron emission tomography (PET) tracer targeting prostate-specific membrane antigen (PSMA) for prostate cancer staging and individualized radiotherapy planning.
A cohort of 57 patients with prostate cancer scanned with (68)Ga-PSMA-11 PET/CT for radiotherapy planning was retrospectively reviewed; 15 patients were at initial diagnosis and 42 patients at time of biochemical recurrence. Staging results of conventional imaging, including bone scintigraphy, CT or MRI, were compared with (68)Ga-PSMA ligand PET/CT results and the influence on radiotherapeutic management was quantified.
(68)Ga-PSMA ligand PET/CT had a dramatic impact on radiotherapy application in the presented cohort. In 50.8 % of the cases therapy was changed.
The presented imaging technique of (68)Ga-PSMA PET/CT could be a key technology for individualized radiotherapy management in prostate cancer.
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