Semiquantitative Parameters in PSMA-Targeted PET Imaging with [18F]DCFPyL: Impact of Tumor Burden on Normal Organ Uptake

Werner, Rudolf A.; Bundschuh, Ralph A.; Bundschuh, Lena; Lapa, Constantin; Yin, Yilong; Javadi, Mehrbod S.; Buck, Andreas K.; Higuchi, Takahiro; Pienta, Kenneth J.; Pomper, Martin G.; Lodge, Martin A.; Gorin, Michael A.; Rowe, Steven P.

doi:10.1007/s11307-019-01375-w

Cited by 31 publications

(35 citation statements)

References 27 publications

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“…Thus, the affinity of the latter agent would be theoretically 30 fold higher compared to [ 18 F]DCFPyL (or 10 fold higher compared to [ 18 F]PSMA-1007). However, human PSMA-targeted PET imaging is a complex interplay of varying factors including biodistribution, radiotracer accumulation in putative sites of disease, renal excretion or normal variant uptake in benign lesions 90. Thus, it is a matter of debate whether IC50 values derived by cell assays indeed reflect clinical reality 74.…”

Section: Part Ii: Recently Introduced 18f-labeled Radiotracersmentioning

confidence: 99%

¹⁸F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging

Werner¹,

Derlin²,

Lapa³

et al. 2020

Theranostics

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135

115

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Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with 68Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world. However, recent years have witnessed the start of a shift from 68Ga- to 18F-labeled PSMA-targeted compounds. The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic. First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite 68Ge/68Ga generator. Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production. Moreover, 18F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions. In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy. Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron. In light of these advantageous characteristics, 18F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available. We have aimed to provide a concise overview of emerging 18F-labeled PSMA-targeted radiotracers undergoing active clinical development. Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available 18F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios.

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Section: Part Ii: Recently Introduced 18f-labeled Radiotracersmentioning

confidence: 99%

¹⁸F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging

Werner¹,

Derlin²,

Lapa³

et al. 2020

Theranostics

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135

115

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“…Another reason why they apply visual interpretations may be because no validated quantitative measurements for [ 68 Ga]Ga-PSMA-11 PET/CT reconstructions are currently available. The use of EARL recommendations for HT-PSMA and TL-PSMA in this study was chosen because, even though these recommendations are used for [ 18 F]-FDG (FDG), the used method for the total lesion glycolysis (TLG) will give the best impression of in vivo distribution of [ 68 Ga]Ga-PSMA-11 by calculating the fractional tumor activity [ 16 , 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…An explanation Pharmaceutics 2021, 13, 699 2 of 11 can be found in the biodistribution of PSMA-tracer as there is also physiological uptake (and therefore irradiation) in healthy tissue such as the kidneys, liver, salivary glands, intestine, and to a lesser degree in the lacrimal glands, spleen, and prostate [9,12,13]. Some have suggested that competition between the uptake of the radiopharmaceutical in prostate tumor tissue and healthy tissue may influence the biodistribution by inducing a 'steal' phenomenon, resulting in diminished uptake in healthy tissue [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Competition (‘Steal’ Phenomenon) between [68Ga]Ga-PSMA-11 Uptake in Prostate Tumor Tissue Versus Healthy Tissue

et al. 2021

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We aimed to clarify whether a steal ‘phenomenon’ exists by investigating if uptake of ‘prostate specific membrane antigen’ (PSMA) in prostate tumor tissue correlates with the uptake in healthy tissue. Patients with prostate cancer referred for a [68Ga]Ga-PSMA-11 PET/CT were identified retrospectively. Semi-automated quantitative image analysis was performed; fractional healthy tissue [68Ga]Ga-PSMA-11 uptake volume (HT-PSMA (SUV*cm3)) in the lacrimal, submandibular, and parotid glands, and kidneys, and the fractional total lesion [68Ga]Ga-PSMA-11 uptake volume (TL-PSMA (SUV*cm3)) of prostate cancer were used. Ninety-two patients, age 78 ± 8 years, were analyzed. Median TL-PSMA was 703.37 SUV*cm3 (IQR 119.56–2778.20), median HT-PSMA of the lacrimal, submandibular, and parotid glands, and kidneys was: 13.69 (IQR 7.29–19.06), 194.75 (IQR 133.67–276.53), 552.54 (IQR 379.98–737.16), and 8092.75 SUV*cm3 (IQR 5793.02–11385.86), respectively. A significant (p-value ≤ 0.001) but weak–moderate correlation was found between the TL-PSMA and HT-PSMA of the parotid- and submandibular glands, and kidneys (correlation coefficient of −0.447,−0.345, and −0.394, respectively). No correlation was found between TL-PSMA and HT-PSMA of the lacrimal glands. The existence of a ‘steal’ phenomenon cannot be confirmed in this study. Healthy tissue uptake of [68Ga]Ga-PSMA-11 is only partially influenced by TL-PSMA. Thus, modification of therapeutic PSMA activity should not be adjusted based on TL-PSMA alone.

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“…Similar to SSTR-directed imaging, recent studies have also reported variable impact of tumor burden among commonly used PSMA-PET/CT radiopharmaceuticals. Gärtner and coworkers reported decreased renal 68 Ga-PSMA-11 uptake in patients with higher tumor burden, whereas renal 18 F-DCFPyL uptake was not similarly affected [65,66]. Again, such discrepant findings with different radiopharmaceuticals highlight the importance of structured reporting systems for patients with different tumor load, as lesions with moderate to faint uptake may be missed, especially close to a normal organ with exaggerated uptake.…”

Section: Common Pitfalls On Sstr- and Psma-pet/ctmentioning

confidence: 99%

Recent Updates on Molecular Imaging Reporting and Data Systems (MI-RADS) for Theranostic Radiotracers—Navigating Pitfalls of SSTR- and PSMA-Targeted PET/CT

Werner

Thackeray

Pomper

et al. 2019

JCM

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The theranostic concept represents a paradigmatic example of personalized treatment. It is based on the use of radiolabeled compounds which can be applied for both diagnostic molecular imaging and subsequent treatment, using different radionuclides for labelling. Clinically relevant examples include somatostatin receptor (SSTR)-targeted imaging and therapy for the treatment of neuroendocrine tumors (NET), as well as prostate-specific membrane antigen (PSMA)-targeted imaging and therapy for the treatment of prostate cancer (PC). As such, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy using positron emission tomography (PET). While interpreting PSMA- or SSTR-targeted PET/computed tomography scans, the reader has to navigate certain pitfalls, including (I.) varying normal biodistribution between different PSMA- and SSTR-targeting PET radiotracers, (II.) varying radiotracer uptake in numerous kinds of both benign and malignant lesions, and (III.) resulting false-positive and false-negative findings. Thus, two novel reporting and data system (RADS) classifications for PSMA- and SSTR-targeted PET imaging (PSMA- and SSTR-RADS) have been recently introduced under the umbrella term molecular imaging reporting and data systems (MI-RADS). Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e., if the reader is familiar with one system, the other system can readily be applied. Learning objectives of the present case-based review are as follows: (I.) the theranostic concept for the treatment of NET and PC will be briefly introduced, (II.) the most common pitfalls on PSMA- and SSTR-targeted PET/CT will be identified, (III.) the novel framework system for theranostic radiotracers (MI-RADS) will be explained, applied to complex clinical cases and recent studies in the field will be highlighted. Finally, current treatment strategies based on MI-RADS will be proposed, which will demonstrate how such a generalizable framework system truly paves the way for clinically meaningful molecular imaging-guided treatment of either PC or NET. Thus, beyond an introduction of MI-RADS, the present review aims to provide an update of recently published studies which have further validated the concept of structured reporting systems in the field of theranostics.

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Semiquantitative Parameters in PSMA-Targeted PET Imaging with [18F]DCFPyL: Impact of Tumor Burden on Normal Organ Uptake

Abstract: Terms of use and reuse: academic research for non-commercial purposes, see here for full terms. http://www.springer.com/gb/openaccess/authors-rights/aam-terms-v1

Cited by 31 publications

References 27 publications

¹⁸F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging

¹⁸F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging

Competition (‘Steal’ Phenomenon) between [68Ga]Ga-PSMA-11 Uptake in Prostate Tumor Tissue Versus Healthy Tissue

Recent Updates on Molecular Imaging Reporting and Data Systems (MI-RADS) for Theranostic Radiotracers—Navigating Pitfalls of SSTR- and PSMA-Targeted PET/CT

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Semiquantitative Parameters in PSMA-Targeted PET Imaging with [18F]DCFPyL: Impact of Tumor Burden on Normal Organ Uptake

Abstract: Terms of use and reuse: academic research for non-commercial purposes, see here for full terms. http://www.springer.com/gb/openaccess/authors-rights/aam-terms-v1

Cited by 31 publications

References 27 publications

18F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging

18F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging

Competition (‘Steal’ Phenomenon) between [68Ga]Ga-PSMA-11 Uptake in Prostate Tumor Tissue Versus Healthy Tissue

Recent Updates on Molecular Imaging Reporting and Data Systems (MI-RADS) for Theranostic Radiotracers—Navigating Pitfalls of SSTR- and PSMA-Targeted PET/CT

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¹⁸F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging

¹⁸F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging