Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. DLBCL exhibits highly aggressive and systemic progression into multiple tissues in patients, particularly in lymph nodes. Whole-body 18F-fluodeoxyglucose positron emission tomography ([18F]FDG-PET) imaging has an essential role in diagnosing DLBCL in the clinic; however, [18F]FDG-PET often faces difficulty in differentiating malignant tissues from certain nonmalignant tissues with high glucose uptake. We have developed a PET imaging strategy for DLBCL that targets poly[ADP ribose] polymerase 1 (PARP1), the expression of which has been found to be much higher in DLBCL than in healthy tissues. In a syngeneic DLBCL mouse model, this PARP1-targeted PET imaging approach allowed us to discriminate between malignant and inflamed lymph nodes, whereas [18F]FDG-PET failed to do so. Our PARP1-targeted PET imaging approach may be an attractive addition to the current PET imaging strategy to differentiate inflammation from malignancy in DLBCL.
#1Brandon Carney(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 9
#2Susanne Kossatz(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 15
Last. Thomas Reiner(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 39
view all 3 authors...
: The poly(adenosine diphosphate-ribose)polymerase (PARP) family of enzymes is an important factor in the cellular DNA damage response and has gained much attention for its role in many diseases, particularly cancer. Targeted molecular imaging of PARP using fluorescent or radiolabeled tags has followed on the success of therapeutic inhibitors and gained momentum over the past few years. This review covers PARP imaging from the very first imaging agents up to the current state of the technology, ...
Diffuse intrinsic pontine glioma (DIPG) is a childhood brainstem tumor with a universally poor prognosis. Here, we characterize a positron emission tomography (PET) probe for imaging DIPG in vivo . In human histological tissues, the probes target, PARP1, was highly expressed in DIPG compared to normal brain. PET imaging allowed for the sensitive detection of DIPG in a genetically engineered mouse model, and probe uptake correlated to histologically determined tumor infiltration. Imaging with the...
Our data support the feasibility of evaluating fluorine 18 fluorthanatrace as a quantifiable biomarker of poly (adenosine diphosphate–ribose) polymerase expression in clinical trials.
Outcomes for patients with refractory diffuse large B cell lymphoma (DLBCL) are poor. In the multicenter ZUMA-1 phase 1 study, we evaluated KTE-C19, an autologous CD3ζ/CD28-based chimeric antigen receptor (CAR) T cell therapy, in patients with refractory DLBCL. Patients received low-dose conditioning chemotherapy with concurrent cyclophosphamide (500 mg/m 2 ) and fludarabine (30 mg/m 2 ) for 3 days followed by KTE-C19 at a target dose of 2 × 10 6 CAR T cells/kg. The incidence of dose-limiting to...
Interim and end-of-treatment PET/CT have become central to the evaluation of Hodgkin and non-Hodgkin lymphoma. This review article seeks to aid clinical decision making by providing an overview of available data on the diagnostic and prognostic value of PET/CT imaging for response assessment and pretransplant evaluation in lymphoma. The relative strengths and limitations of these techniques in various disease subtypes and clinical scenarios are explored, along with their current standards for re...
Publisher's Note: There is an [Inside Blood Commentary][1] on this article in this issue. Uniformly adopted response criteria are essential for assessment of therapies incorporating conventional chemotherapy and chemoimmunotherapy regimens. Recently, immunomodulatory agents, such as immune checkpoint inhibitors, have demonstrated impressive activity in a broad range of lymphoma histologies. However, these agents may be associated with clinical and imaging findings during treatment suggestive of ...
#1Jun Tang(ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 27
#2Samantha Baxter(ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 7
Last. Willem J. M. Mulder(ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 73
view all 23 authors...
Immunological complexity in atherosclerosis warrants targeted treatment of specific inflammatory cells that aggravate the disease. With the initiation of large phase III trials investigating immunomodulatory drugs for atherosclerosis, cardiovascular disease treatment enters a new era. We here propose a radically different approach: implementing and evaluating in vivo a combinatorial library of nanoparticles with distinct physiochemical properties and differential immune cell specificities. The l...
Last. John M. Timmerman(UCLA: University of California, Los Angeles)H-Index: 41
view all 23 authors...
PurposeCancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies.MethodsIn this phase I, open-label, dose-escalation, cohort-expansion study, pati...
Last. Ahmedin Jemal(ACS: American Cancer Society)H-Index: 139
view all 9 authors...
The number of cancer survivors continues to increase because of both advances in early detection and treatment and the aging and growth of the population. For the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborate to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results cancer registries. In addition, current treatment patterns for the most prevalen...
The application of nanoparticle drug formulations, such as nanoliposomal doxorubicin (Doxil), is increasingly integrated in clinical cancer care. Despite nanomedicine's remarkable potential and growth over the last three decades, its clinical benefits for cancer patients vary. Here we report a non-invasive quantitative positron emission tomography (PET) nanoreporter technology that is predictive of therapeutic outcome in individual subjects. In a breast cancer mouse model, we demonstrate that co...
#2Navjot Guru(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 4
Last. Elizabeth L. Jewell(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 22
view all 12 authors...
Despite efforts in prevention, cervical cancer still presents with a high worldwide incidence and remains a great problem in public health, especially in low-income countries. Screening programs, such as colposcopy with Papanicolaou testing, have greatly improved mortality rates. However, the agents currently used to delineate those lesions (topical application of acetic acid and/or Lugol's iodine) lack specificity and sometimes can lead to unnecessary biopsies or even cervical excisions. A tool...
Last. Bhupinder Sharma(The Royal Marsden NHS Foundation Trust)H-Index: 16
view all 10 authors...
Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in adults. It is a malignancy of CD5 B-cells characterised by small, mature-appearing lymphocytes accumulating in the blood, bone marrow, and lymphoid tissues. Richer transformation (RT) is an important adverse complication. Detection of RT is critical to allow initiation of appropriate therapy. CLL staging and response evaluation is complicated and nuanced. From our extensive tertiary centre experience of several hundred CLL cases...
#2Susanne Kossatz(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 15
Last. Thomas Reiner(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 39
view all 15 authors...
BACKGROUND Visual inspection and biopsy is the current standard of care for oral cancer diagnosis, but is subject to misinterpretation and consequently to misdiagnosis. Topically applied PARPi-FL is a molecularly specific, fluorescent contrast-based approach that may fulfill the unmet need for a simple, in vivo, non-invasive, cost-effective, point-of-care method for the early diagnosis of oral cancer. Here, we present results from a phase I safety and feasibility study on fluorescent, topically ...
#1Laura Puentes(UPenn: University of Pennsylvania)H-Index: 4
#2Mehran Makvandi(UPenn: University of Pennsylvania)H-Index: 14
Last. Robert H. Mach(UPenn: University of Pennsylvania)H-Index: 60
view all 3 authors...
The genetic code to life is balanced on a string of DNA that is under constant metabolic and physical stress from environmental forces. Nearly all diseases have a genetic component caused by or resulting in DNA damage that alters biology to drive pathogenesis. Recent advancements in DNA repair biology have led to the development of imaging tools that target DNA damage response and repair proteins. Positron-emission tomography (PET) has been used for early detection of oncogenic processes and mon...
Abstract Purpose Visual inspection and biopsy is the current standard of care for oral cancer diagnosis, but is subject to misinterpretation and consequently to misdiagnosis. Topically applied PARPi-FL is a molecularly specific, fluorescent contrast-based approach that may fulfil the unmet need for a simple, in vivo, non-invasive, cost-effective, point-of-care method for the early diagnosis of oral cancer. Here, we present results from a phase I safety and feasibility study on fluorescent, topic...
Last. Mark Dunphy(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 17
view all 20 authors...
We report pre-clinical and first-in-human-brain-cancer data using a targeted poly(ADP-ribose)polymerase1 (PARP1) binding PET tracer, [18F]PARPi, as a diagnostic tool to differentiate between brain cancers and treatment related changes. In a pre-clinical mouse model, we illustrated that [18F]PARPi crosses the blood-brain barrier and specifically binds to PARP1 overexpressed in cancer cell nuclei. In humans, we demonstrated high [18F]PARPi uptake on PET/MR in active brain cancers and low uptake in...
The central paradigm of novel therapeutic approaches in cancer therapy is identifying and targeting molecular biomarkers. One such target is the nuclear DNA repair enzyme Poly-(ADP ribose) polymerase 1 (PARP1). Sensitivity to PARP inhibition in certain cancers such as gBRCAmut breast and ovarian cancers has led to its exploitation as a target. The overexpression of PARP1 in several types of cancer further evoked interest in its use as an imaging target. While PARP1-targeted inhibitors have fast ...
#1Thomas C. Wilson(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 1
#1Thomas C. Wilson(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 1
Last. Giacomo Pirovano(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 9
view all 6 authors...
Purpose:123I-MAPi, a novel PARP1-targeted Auger radiotherapeutic has shown promising results in pre-clinical glioma model. Currently 123I-MAPi is synthesized using multistep synthesis that results in modest yields and low molar activities that limits the ability to translate this technology for human studies where high doses are administered. Therefore, new methods are needed to synthesize 123I-MAPi in high activity yields and improved molar activities to facilitate clinical translation and mult...
Purpose: Glioblastoma multiforme is a highly aggressive form of brain cancer whose location, tendency to infiltrate healthy surrounding tissue, and heterogeneity significantly limit survival, with scant progress having been made in recent decades. Experimental design: 123 I-MAPi (Iodine-123 Meitner-Auger PARP1 inhibitor) is a precise therapeutic tool composed of a PARP1 inhibitor radiolabeled with an Auger- and gamma-emitting iodine isotope. Here, the PARP inhibitor, which binds to the DNA repai...
Abstract Objectives The evaluation of disease extent and post-therapy surveillance of head and neck cancer using 2-deoxy-2-[18F]fluoro- d -glucose ([18F]FDG) PET is often complicated by physiological uptake in normal tissues of the head and neck region, especially after surgery or radiotherapy. However, irrespective of low positive predictive values, [18F]FDG PET remains the standard of care to stage the disease and monitor recurrences. Here, we report the preclinical use of a targeted poly (ADP...