Benzyl-methyl-tetrazole Ligands of Autotaxin for PET Imaging Techniques and Diagnostic

Prostate-specific membrane antigen (PSMA) is a glycoprotein present in the prostate, that is overexpressed in prostate cancer (PCa). Recently, PSMA-directed radiopharmaceuticals have been developed, allowing the pinpointing of tumors with the Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) imaging techniques. The aim of the present work was to standardize and validate an automatic synthesis module-based radiolabeling protocol for [68Ga]Ga-PSMA-11, as well as to produce a radiopharmaceutical for PET imaging of PCa malignancies. [68Ga]Ga-PSMA-11 was evaluated to determine the radiochemical purity (RCP), stability in saline solution and serum, lipophilicity, affinity to serum proteins, binding and internalization to lymph node carcinoma of the prostate (LNCaP) cells, and ex vivo biodistribution in mice. The radiopharmaceutical was produced with an RCP of 99.06 ± 0.10%, which was assessed with reversed-phase high-performance liquid chromatography (RP-HPLC). The product was stable in saline solution for up to 4 h (RCP > 98%) and in serum for up to 1 h (RCP > 95%). The lipophilicity was determined as −3.80 ± 0.15, while the serum protein binding (SPB) was <17%. The percentages of binding to LNCaP cells were 4.07 ± 0.51% (30 min) and 4.56 ± 0.46% (60 min), while 19.22 ± 2.73% (30 min) and 16.85 ± 1.34% (60 min) of bound material was internalized. High accumulation of [68Ga]Ga-PSMA-11 was observed in the kidneys, spleen, and tumor, with a tumor-to-contralateral-muscle ratio of >8.5 and a tumor-to-blood ratio of >3.5. In conclusion, an automatic synthesis module-based radiolabeling protocol for [68Ga]Ga-PSMA-11 was standardized and the product was evaluated, thus verifying its characteristics for PET imaging of PCa tumors in a clinical environment.

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Pattern of failure in prostate cancer previously treated with radical prostatectomy and post-operative radiotherapy: a secondary analysis of two prospective studies using novel molecular imaging techniques

Radiation Oncology ◽

10.1186/s13014-020-01733-x ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Lindsay S. Rowe ◽

Stephanie Harmon ◽

Adam Horn ◽

Uma Shankavaram ◽

Soumyajit Roy ◽

...

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

Pet Imaging ◽

Biochemical Recurrence ◽

Imaging Techniques ◽

Specific Antigen ◽

Definitive Treatment ◽

Pattern Of Failure ◽

Link Type ◽

Psma Pet

Abstract Background Prostate Membrane Specific Antigen (PSMA) positron emission tomography (PET) and multiparametric MRI (mpMRI) have shown high accuracy in identifying recurrent lesions after definitive treatment in prostate cancer (PCa). In this study, we aimed to outline patterns of failure in a group of post-prostatectomy patients who received adjuvant or salvage radiation therapy (PORT) and subsequently experienced biochemical recurrence, using 18F-PSMA PET/CT and mpMRI. Methods PCa patients with biochemical failure post-prostatectomy, and no evident site of recurrence on conventional imaging, were enrolled on two prospective trials of first and second generation 18F-PSMA PET agents (18F-DCFBC and 18F-DCFPyL) in combination with MRI between October 2014 and December 2018. The primary aim of our study is to characterize these lesions with respect to their location relative to previous PORT field and received dose. Results A total of 34 participants underwent 18F-PSMA PET imaging for biochemical recurrence after radical prostatectomy and PORT, with 32/34 found to have 18F-PSMA avid lesions. On 18F-PSMA, 17/32 patients (53.1%) had metastatic disease, 8/32 (25.0%) patients had locoregional recurrences, and 7/32 (21.9%) had local failure in the prostate fossa. On further exploration, we noted 6/7 (86%) of prostate fossa recurrences were in-field and were encompassed by 100% isodose lines, receiving 64.8–72 Gy. One patient had marginal failure encompassed by the 49 Gy isodose. Conclusions 18F-PSMA PET imaging demonstrates promise in identifying occult PCa recurrence after PORT. Although distant recurrence was the predominant pattern of failure, in-field recurrence was noted in approximately 1/5th of patients. This should be considered in tailoring radiotherapy practice after prostatectomy. Trial registrationwww.clinicaltrials.gov, NCT02190279 and NCT03181867. Registered July 12, 2014, https://clinicaltrials.gov/ct2/show/NCT02190279 and June 8 2017, https://clinicaltrials.gov/ct2/show/NCT03181867.

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Novel Quantitative PET Imaging Techniques in Tuberculosis

PET Clinics ◽

10.1016/j.cpet.2019.11.010 ◽

2020 ◽

Vol 15 (2) ◽

pp. 231-240

Author(s):

Viplav Deogaonkar ◽

Bangkim Chandra Khangembam ◽

Siavash Mehdizadeh Seraj ◽

Abass Alavi ◽

Rakesh Kumar ◽

...

Keyword(s):

Pet Imaging ◽

Imaging Techniques ◽

Quantitative Pet

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Unparalleled and revolutionary impact of PET imaging on research and day to day practice of medicine

Bio-Algorithms and Med-Systems ◽

10.1515/bams-2021-0186 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Abass Alavi ◽

Thomas J. Werner ◽

Ewa Ł. Stępień ◽

Pawel Moskal

Keyword(s):

Molecular Imaging ◽

Pet Imaging ◽

Imaging Techniques ◽

The Body ◽

Therapeutic Interventions ◽

University Of Pennsylvania ◽

Positron Emission ◽

Practice Of Medicine ◽

Pet Instrumentation ◽

Total Body

Abstract Positron emission tomography (PET) imaging is the most quantitative modality for assessing disease activity at the molecular and cellular levels, and therefore, it allows monitoring its course and determining the efficacy of various therapeutic interventions. In this scientific communication, we describe the unparalleled and revolutionary impact of PET imaging on research and day to day practice of medicine. We emphasize the critical importance of the development and synthesis of novel radiotracers (starting from the enormous impact of F-Fluorodeouxyglucose (FDG) introduced by investigators at the University of Pennsylvania (PENN)) and PET instrumentation. These innovations have led to the total-body PET systems enabling dynamic and parametric molecular imaging of all organs in the body simultaneously. We also present our perspectives for future development of molecular imaging by multiphoton PET systems that will enable users to extract substantial information (owing to the evolving role of positronium imaging) about the related molecular and biological bases of various disorders, which are unachievable by the current PET imaging techniques.

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Hypoxia PET imaging techniques: data acquisition and analysis

Clinical and Translational Imaging ◽

10.1007/s40336-017-0250-y ◽

2017 ◽

Vol 5 (6) ◽

pp. 489-496 ◽

Cited By ~ 2

Author(s):

Daniela Thorwarth ◽

Linda-Jacqueline Wack ◽

David Mönnich

Keyword(s):

Data Acquisition ◽

Pet Imaging ◽

Imaging Techniques

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Visualizing epigenetics: Current advances and advantages in HDAC PET imaging techniques

Neuroscience ◽

10.1016/j.neuroscience.2013.09.018 ◽

2014 ◽

Vol 264 ◽

pp. 186-197 ◽

Cited By ~ 26

Author(s):

C. Wang ◽

F.A. Schroeder ◽

J.M. Hooker

Keyword(s):

Pet Imaging ◽

Imaging Techniques

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62cuatsm and 62cuptsm PET is a useful imaging tool for hypoxia and perfusion in lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e22166 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e22166-e22166

Author(s):

Tian Zhang ◽

Shiva K. Das ◽

Jeffrey Crawford ◽

Terence Wong ◽

Mark W. Dewhirst ◽

...

Keyword(s):

Pet Imaging ◽

Lung Tumor ◽

Imaging Techniques ◽

Small Sample Size ◽

Medical Center ◽

Clinical Care ◽

Tumor Hypoxia ◽

Small Sample ◽

Unique Challenge ◽

Pet Scans

e22166 Background: Hypoxia is a characteristic of many tumors and portends a worse prognosis in lung, cervical, prostate, and rectal cancers. Unlike the others, lung cancers present a unique challenge in measuring hypoxia, with invasive biopsies and higher rates of complications. Noninvasive imaging studies detecting hypoxia using isotopes of copper-diacetyl-bis (N4-methylthiosemicarbazone), CuATSM, have predicted prognosis and treatment outcomes in some small feasibility trials. These images, however, may not identify all areas of hypoxia. Hence, we hypothesize that the addition of another positron emission tomography (PET) imaging agent, copper-pyruvaldehyde-bis (N4-methylthiosemicarbazone), 62CuPTSM, which can detect areas of perfusion, can augment the information obtained in 62CuATSM PET scans. Methods: In order to characterize tumors based on both perfusion and hypoxia, ten patients were studied using both 62CuATSM and 62CuPTSM PET scans. All patients signed informed consent; the protocol was approved by the Duke University Medical Center institutional review board. 62CuATSM and 62CuPTSM SUV values at steady state were tabulated and the ratios of 62CuATSM to 62CuPTSM calculated. In addition, proteomic arrays looking at specific proangiogenic, survival, and proinflammatory targets were assessed. Results: Six out of ten patients had fully evaluable PET scans. Our initial experience of characterizing lung tumor hypoxia using 62CuATSM/62CuPTSM PET scans showed that visualization of areas with hypoxia normalized for perfusion is feasible. All studied tumors exhibited some hypoxia. Despite the small sample size, a positive relationship was noted between serum epidermal growth factor (EGF) levels and 62CuATSM detected hypoxia. Conclusions: This initial series of 62CuATSM/62CuPTSM PET scans demonstrate that evaluating pulmonary lesions by visualizing hypoxia and perfusion is a feasible and novel technique to provide more information. Further investigation is warranted to assess the potential role of 62CuATSM and 62CuPTSM PET imaging techniques combined with proteomics as alternatives to invasive biopsy techniques in clinical care.

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Quantification of tumour hypoxia

Nuklearmedizin ◽

10.1055/s-0038-1626532 ◽

2010 ◽

Vol 49 (S 01) ◽

pp. S37-S40

Author(s):

J. Bussink

Keyword(s):

Pet Imaging ◽

Imaging Techniques ◽

Intensity Modulated Radiotherapy ◽

Tumour Hypoxia ◽

Cancer Treatments ◽

Intensity Modulated ◽

Pet Ct ◽

Anti Cancer ◽

Cell Hypoxia ◽

Microscopic Techniques

SummaryTumor cell hypoxia is considered one of the important causes for radiation resistance. The introduction of IMRT (intensity modulated radiotherapy) allows specific boosting of tumor subvolumes that may harbour these radioresistant tumour cells. PET imaging of these subvolumes can be incorporated into treatment planning.However, at this moment microenvironmental changes visualized and quantified by means of PET-imaging need to be validated by highresolution microscopic techniques. This will allow interpretation of imaging techniques with intermediate resolution (such as PET/CT) in relation to complex cellular signaling in response to anti-cancer treatments.

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SCIDOT-29. EVALUATING THE FEASIBILITY OF INTRANASAL FLT DELIVERY FOR PET IMAGING OF PRIMARY BRAIN TUMORS

Neuro-Oncology ◽

10.1093/neuonc/noz175.1165 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi277-vi277

Author(s):

Grant Carlisle ◽

Austin Fowler ◽

Joel Soma ◽

Lester Drewes ◽

Bret Friday

Keyword(s):

Brain Tumors ◽

Olfactory Bulb ◽

Pet Imaging ◽

Drug Targeting ◽

Imaging Techniques ◽

Tumor Resection ◽

Brain Regions ◽

Pharmacokinetic Parameters ◽

Primary Brain Tumors ◽

Dismal Prognosis

Abstract INTRODUCTION Glioblastoma (GBM) is an aggressive primary brain tumor with a dismal prognosis. Overall survival rates have been correlated to initial tumor resection making improved imaging techniques necessary for improved patient outcomes. Functional imaging with fluorothymidine (FLT) has been limited due to inefficient transfer through the blood-brain-barrier. In this experiment, we strived to test the efficacy of tritium-labeled-FLT (3H-FLT) delivery to brain tissue through intranasal (IN) versus intravenous (IV) administration in a rat model. METHODS Adult rats (Sprague Dawley, 180-200g) received 3H-FLT through either an IN or IV delivery method. At 5, 20, and 60 minutes, concentrations of 3H-FLT were measured in 16 brain regions as well as blood and non-target organs via isotope quantitation using scintillation detection. Pharmacokinetic parameters were calculated. RESULTS Intranasal olfactory bulb concentrations of 3H-FLT trended higher compared to IV olfactory bulb. All other brain region concentrations were insignificantly different. Kp (brain-blood ratio) values mimicked this trend. Secondary calculations were performed to evaluate intranasal CNS drug targeting. Initial trends showed a more effective IN drug penetration to the olfactory bulb, spinal cord, and hippocampus. Drug targeting efficiency (DTE%) was found to be highest in the olfactory bulb at 212%, but all other brain regions were greater than 100% suggesting more efficient drug targeting with intranasal administration. Nose-to-brain direct transport percentage (DTP%), and comparative brain bioavailability (B%) showed similar trends. Non-target tissues including heart, lung, adipose and skeletal muscle were collected in the 5- and 60-minute trials and found to be significantly higher than all brain concentrations. CONCLUSION Drug delivery calculations suggest increased efficacy with IN administration of FLT to all brain regions compared to IV administration. However, additional optimization is likely necessary to improve PET imaging of primary brain tumors using IN delivery due to the relatively small differences observed.

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