PSMA PET and Radionuclide Therapy in Prostate Cancer Bouchelouche, Kirsten, MD, DMSc; Turkbey, Baris, MD, FSAR; Choyke, Peter L., MD FACR
Seminars in nuclear medicine,
11/2016, Letnik:
46, Številka:
6
Journal Article
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Prostate cancer (PCa) is the most common malignancy in men and a major cause of cancer death. Accurate imaging plays an important role in diagnosis, staging, restaging, detection of biochemical ...recurrence, and for therapy of patients with PCa. Because no effective treatment is available for advanced PCa, there is an urgent need to develop new and more effective therapeutic strategies. To optimize treatment outcome, especially in high-risk patients with PCa, therapy for PCa is moving rapidly toward personalization. Medical imaging, including positron emission tomography (PET)/computed tomography (CT), plays an important role in personalized medicine in oncology. In the recent years, much focus has been on prostate-specific membrane antigen (PSMA) as a promising target for imaging and therapy with radionuclides, as it is upregulated in most PCa. In the prostate, one potential role for PSMA PET imaging is to help guide focal therapy. Several studies have shown great potential of PSMA PET/CT for initial staging, lymph node staging, and detection of recurrence of PCa, even at very low prostate-specific antigen values after primary therapy. Furthermore, studies have shown that PSMA PET/CT has a higher detection rate than choline PET/CT. Radiolabeled PSMA ligands for therapy show promise in several studies with metastatic PCa and is an area of active investigation. The “image and treat” strategy, with radiolabeled PSMA ligands, has the potential to improve the treatment outcome of patients with PCa and is paving the way for precision medicine in PCa. The aim of this review is to give an overview of recent advancement in PSMA PET and radionuclide therapy for PCa.
Abstract Polyethylene glycol (PEG) surface modification can make nanomaterials highly hydrophilic, reducing their sequestration in the reticuloendothelial system. In this study, polyamidoamine ...(PAMAM) dendrimers bearing gadolinium (Gd) chelates were PEGylated with different PEG-chain lengths, and the effects on paramagnetic and pharmacokinetic properties were evaluated. Specifically, Gd chelate-bearing PAMAM dendrimers (generations 4 and 5; G4 and G5) were conjugated with two different PEG chains (2 kDa and 5 kDa; 2k and 5k). Long PEG chains (5k) on the smaller (G4) dendrimer resulted in reduced relaxivity compared to non-PEGylated dendrimers, whereas short PEG chains (2k) on a larger (G5) dendrimer produced relaxivities comparable to non-PEGylated G4 dendrimers. The relaxivity of all PEGylated or lysine-conjugated dendrimers increased at higher temperature, whereas that of intact G4 Gd-PAMAM dendrimer decreased. All PEGylated dendrimers had minimal liver and kidney uptake and remained in circulation for at least 1 hour. Thus, surface-PEGylated Gd-PAMAM dendrimers showed decreased plasma clearance and prolonged retention in the blood pool. Shorter PEG, higher generation conjugates led to higher relaxivity. From the Clinical Editor In this study, polyamidoamine dendrimers bearing gadolinium (Gd) chelates were PEGylated with different PEG-chain lengths, and the effects on paramagnetic and pharmacokinetic properties were evaluated.
Summary The development of imaging technologies that have sufficient specificity and sensitivity to enable early, accurate detection of cancer and response to therapy has long been a goal in ...oncology. Various radiological techniques have been used for diagnosis and surveillance of disease recurrence and imaging has revolutionised oncology. However, despite the widespread use of technologies, the ability of currently available imaging methods to facilitate early detection, precise characterisation, and accurate localisation of maligant disease could be improved. The simultaneous use of two or more techniques, contrast reagents, signalling methods, or the coupling of agent and tissue properties to achieve so-called multiplexed imaging is a promising approach. In this review, we provide a broad overview of current and emerging multiplexed, imaging technologies.
Objective:
The goal is to evaluate avelumab, an anti-PD-L1 monoclonal immunoglobulin G antibody labeled with zirconium-89 in human PD-L1-expressing cancer cells and mouse xenografts for clinical ...translation.
Methods:
89ZrZr-DFO-PD-L1 monoclonal antibody (mAb) was synthesized using avelumab conjugated to desferrioxamine. In vitro binding studies and biodistribution studies were performed with PD-L1+MDA-MB231 cells and MDA-MB231 xenograft mouse models, respectively. Biodistributions were determined at 1, 2, 3, 5, and 7 days post coinjection of 89ZrZr-DFO-PD-L1 mAb without or with unlabeled avelumab (10, 20, 40, and 400 µg).
Results:
89ZrZr-DFO-PD-L1 mAb exhibited high affinity (Kd ∼ 0.3 nM) and detected moderate PD-L1 expression levels in MDA-MB231 cells. The spleen and lymph nodes exhibited the highest 89ZrZr-DFO-PD-L1 mAb uptakes in all time points, while MDA-MB231 tumor uptakes were lower but highly retained. In the unlabeled avelumab dose escalation studies, spleen tissue–muscle ratios decreased in a dose-dependent manner indicating specific 89ZrZr-DFO-PD-L1 mAb binding to PD-L1. In contrast, lymph node and tumor tissue–muscle ratios increased 4- to 5-fold at 20 and 40 µg avelumab doses.
Conclusions:
89ZrZr-DFO-PD-L1 mAb exhibited specific and high affinity for PD-L1 in vitro and had target tissue uptakes correlating with PD-L1 expression levels in vivo. 89ZrZr-DFO-PD-L1 mAb uptake in PD-L1+tumors increased with escalating doses of avelumab.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Imaging plays an important role in the clinical management of cancer patients. Hybrid imaging with PET/computed tomography (CT) is having a broad impact in oncology, and in recent years PET/CT is ...beginning to have an impact in urooncology. In both bladder and renal cancers, there is a need to study the efficacy of other tracers than F-18 fluorodeoxyglucose (FDG), particularly tracers with limited renal excretion. Thus, new tracers are being introduced. This review focuses on the clinical role of FDG and other PET agents in renal, bladder, and testicular cancers.
Malignant mesothelioma (MM) of the pleura is an aggressive and often fatal neoplasm. Because MM frequently demonstrates marked angiogenesis, it may be responsive to antiangiogenic therapy, but ...effective methods for selecting and monitoring of patients are further needed. We employed dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and quantitative immunohistochemistry (IHC) to characterize the microvascularity of MM using both a physiologic and ultrastructural method.
Nineteen patients diagnosed with MM were enrolled and DCE-MRI was performed before antiangiogenic treatment. For each patient, tumor regions were characterized by their DCE-MRI-derived pharmacokinetic parameters (Amp, k(ep), k(el)), which were also compared to those of normal tissue (aorta, liver, spleen, and muscle). In addition, quantitative IHC of representative samples was performed with CD-34 staining to compare the calculated microvessel density (MVD) results with DCE-MRI results.
MM demonstrated markedly abnormal pharmacokinetic properties compared with normal tissues. Among the parameters tested, Amp was significantly different in MM (P < or = .001) compared to normal organs. Despite the observation that the MVD of mesotheliomas in this series was high compared to other tumors, DCE-MRI pharmacokinetic parameters had a moderately positive correlation with MVD (r = 0.5).
DCE-MRI and IHC can be used in patients with MM to visualize tumor microvascularity and to characterize tumor heterogeneity. DCE-MRI and IHC results positively correlated, though moderately, but these two methods present as essential tumor biomarkers. This multimodal characterization may be useful in selecting possible tumor subtypes that would benefit from antiangiogenic therapy.
Background:
Near-infrared photoimmunotherapy (NIR-PIT) is a cancer therapy that causes an increase in tumor perfusion, a phenomenon termed the super-enhanced permeability and retention effect. ...Currently, in vivo treatment efficacy of NIR-PIT is observable days after treatment, but monitoring would be improved by more acute detection of intratumor change. Fluorescence imaging may detect increased tumor perfusion immediately after treatment.
Methods:
In the first experiment, athymic nude mouse models bearing unilateral subcutaneous flank tumors were treated with either NIR-PIT or laser therapy only. In the second experiment, mice bearing bilateral flank tumors were treated with NIR-PIT only on the left-sided tumor. In both groups, immediately after treatment, indocyanine green was injected at different doses intravenously, and mice were monitored with the Shimadzu LIGHTVISION fluorescence imaging system for 1 hour.
Results:
Tumor-to-background ratio of fluorescence intensity increased over the 60 minutes of monitoring in treated mice but did not vary significantly in control mice. Tumor-to-background ratio was highest in the 1 mg kg−1 and 0.3 mg kg−1 doses. In mice with bilateral tumors, tumor-to-untreated tumor ratio increased similarly.
Conclusions:
Acute changes in tumor perfusion after NIR-PIT can be detected by real-time fluorescence imaging.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Prostate biopsies are usually performed by urologists in the office setting using transrectal ultrasound (US) guidance. The current standard of care involves obtaining 10-14 cores from different ...anatomic sections. Biopsies are usually not directed into a specific lesion because most prostate cancers are not visible on transrectal US. Color Doppler, US contrast agents, elastography, magnetic resonance (MR) imaging, and MR imaging/US fusion are proposed as imaging methods to guide prostate biopsies. Prostate MR imaging and fusion biopsy create opportunities for diagnostic and interventional radiologists to play an increasingly important role in the screening, evaluation, diagnosis, targeted biopsy, surveillance, and focal therapy of patients with prostate cancer.
Background Patients with von Hippel-Lindau disease (VHL) commonly develop pancreatic cysts and neuroendocrine neoplasms (PNENs or PNETs). Solid microcystic serous adenoma (SMSA), a rare neoplasm ...described in VHL patients, can be mistaken for PNEN on imaging. Methods Clinical, pathologic, and radiologic data were reviewed on VHL patients who underwent surgery for a preoperative diagnosis of PNEN since 1994 at 1 institution. Blinded to the pathologic diagnoses, radiologists reassessed available imaging. Results For 55 patients, 79 pancreatectomies were performed for presumed PNENs. Ten (18%) patients underwent 12 (15%) resections for neoplasms diagnosed as SMSA on final pathology. The average size of a SMSA leading to operation was 3.6 ± 0.4 cm. Four out of 11 SMSAs were still mistaken for PNENs when imaging was reassessed. The mean FDG-positron emission tomography (PET) standardized uptake value was greater for 17 PNENs (12.1 ± 1.2) compared with 6 SMSAs (4.2 ± 0.5; P = .002). The mean doubling time of SMSAs and PNENs was similar. Seven (15%) patients with pathologically proven PNENs had malignant disease. Conclusion SMSAs can mimic PNENs on nonfunctional imaging; FDG-PET may help to differentiate them. A high index of suspicion is needed to minimize operations performed for SMSA and to counsel VHL patients of their risks of undergoing operation for a lesion with no known malignant potential.
Abstract Purpose Multiparametric MRI (mpMRI) and fusion biopsy (FBx) detect more high-risk prostate cancer (PCa) and less low-risk PCa than systematic biopsy (SBx). However, there remains a small ...subset of patients where SBx captures higher grade disease than FBx. We aim to identify potential mechanisms for failure of FBx biopsy in detection of clinically significant (CS) PCa. Methods We reviewed a prospectively maintained database of patients undergoing mpMRI followed by FBx and SBx from 2007-2014. In patients disease upgraded to CS disease (Gleason ≥ 7) by SBx over FBx, independent re-review of MR imaging, archived biopsy imaging, and whole mount pathology, as well as needle coordinate mapping were conducted. Multivariate logistic regression analysis was performed to determine predictors for upgrading by SBx. Results Disease upgrading based on SBx over FBx occurred in 135/1003 (13.5%) patients, of which only 62 (6.2%) were to intermediate (Gleason=7) N=51, 5.1% or high risk PCa (Gleason≥8) N=11, 1.1%. On multivariate analysis, lower PSA (p <0.001), higher MRI prostate volume (p <0.001), and lower number of target cores (p=0.001) were predictors of upgrading by SBx. Main mechanisms for under-grading by FBx included mpMRI reader oversight, presence of MR invisible cancer, FBx technique error, and intra-lesion Gleason heterogeneity. Conclusions MRI and FBx rarely misses CS PCa, as only 62/1003 (6.2%) cases were upgraded to CS disease by SBx. Imaging and biopsy techniques are continually refined and further studies will help to clarify mechanisms of FBx failure and patient populations which benefit from SBx in addition to FBx.
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