Novel Quantitative PET Imaging Techniques in Tuberculosis

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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Quantitative PET imaging of radioligands with slow kinetics in human brain

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-010-1518-x ◽

2010 ◽

Vol 37 (8) ◽

pp. 1613-1615 ◽

Cited By ~ 3

Author(s):

Sandra M. Sanabria-Bohórquez ◽

Koen Van Laere

Keyword(s):

Human Brain ◽

Pet Imaging ◽

Quantitative Pet ◽

Slow Kinetics

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Cardiac motion and spillover correction for quantitative PET imaging using dynamic MRI

Medical Physics ◽

10.1002/mp.13345 ◽

2019 ◽

Vol 46 (2) ◽

pp. 726-737 ◽

Cited By ~ 1

Author(s):

Stephanie Marchesseau ◽

John J. Totman ◽

Hakim Fadil ◽

Francesca A. A. Leek ◽

Jasper Chaal ◽

...

Keyword(s):

Pet Imaging ◽

Dynamic Mri ◽

Cardiac Motion ◽

Quantitative Pet ◽

Spillover Correction

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Quantitative PET imaging of PD-L1 expression in xenograft and syngeneic tumour models using a site-specifically labelled PD-L1 antibody

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-019-04646-4 ◽

2019 ◽

Vol 47 (5) ◽

pp. 1302-1313 ◽

Cited By ~ 5

Author(s):

Camilla Christensen ◽

Lotte K. Kristensen ◽

Maria Z. Alfsen ◽

Carsten H. Nielsen ◽

Andreas Kjaer

Keyword(s):

Pet Imaging ◽

Predictive Value ◽

Ex Vivo ◽

Response To Therapy ◽

Whole Body ◽

Therapeutic Monitoring ◽

Non Invasive ◽

Tumour Bearing ◽

Quantitative Pet

Abstract Purpose Despite remarkable clinical responses and prolonged survival across several cancers, not all patients benefit from PD-1/PD-L1 immune checkpoint blockade. Accordingly, assessment of tumour PD-L1 expression by immunohistochemistry (IHC) is increasingly applied to guide patient selection, therapeutic monitoring, and improve overall response rates. However, tissue-based methods are invasive and prone to sampling error. We therefore developed a PET radiotracer to specifically detect PD-L1 expression in a non-invasive manner, which could be of diagnostic and predictive value. Methods Anti-PD-L1 (clone 6E11, Genentech) was site-specifically conjugated with DIBO-DFO and radiolabelled with 89Zr (89Zr-DFO-6E11). 89Zr-DFO-6E11 was optimized in vivo by longitudinal PET imaging and dose escalation with excess unlabelled 6E11 in HCC827 tumour-bearing mice. Specificity of 89Zr-DFO-6E11 was evaluated in NSCLC xenografts and syngeneic tumour models with different levels of PD-L1 expression. In vivo imaging data was supported by ex vivo biodistribution, flow cytometry, and IHC. To evaluate the predictive value of 89Zr-DFO-6E11 PET imaging, CT26 tumour-bearing mice were subjected to external radiation therapy (XRT) in combination with PD-L1 blockade. Results 89Zr-DFO-6E11 was successfully labelled with a high radiochemical purity. The HCC827 tumours and lymphoid tissue were identified by 89Zr-DFO-6E11 PET imaging, and co-injection with 6E11 increased the relative tumour uptake and decreased the splenic uptake. 89Zr-DFO-6E11 detected the differences in PD-L1 expression among tumour models as evaluated by ex vivo methods. 89Zr-DFO-6E11 quantified the increase in PD-L1 expression in tumours and spleens of irradiated mice. XRT and anti-PD-L1 therapy effectively inhibited tumour growth in CT26 tumour-bearing mice (p < 0.01), and the maximum 89Zr-DFO-6E11 tumour-to-muscle ratio correlated with response to therapy (p = 0.0252). Conclusion PET imaging with 89Zr-DFO-6E11 is an attractive approach for specific, non-invasive, whole-body visualization of PD-L1 expression. PD-L1 expression can be modulated by radiotherapy regimens and 89Zr-DFO-6E11 PET is able to monitor these changes and predict the response to therapy in an immunocompetent tumour model.

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