Normal distribution pattern and physiological variants of 68Ga-PSMA-11 PET/CT imaging

Demirci, Emre; Şahin, Onur Erdem; Ocak, Meltem; Akovalı, Burak; Nematyazar, Jamal; Kabasakal, Levent

doi:10.1097/mnm.0000000000000566

Cited by 131 publications

(107 citation statements)

References 21 publications

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“…No cancer cells except one case of PDTC were immunoreactive for PSMA. No normal thyroid epithelium or non-neoplastic microvasculature were PSMA-positive, which is in the line with the recent biodistribution study that found minimal uptake of 68 Ga-PSMA-11 PET/CT radiotracer in thyroid in 56 patients compared to significantly higher uptake in thyroid nodules 32 . PSMA expression in neovasculature was observed in a wide spectrum of thyroid tumors from benign adenomas to highly-aggressive undifferentiated carcinomas.…”

Section: Discussionsupporting

confidence: 91%

“…Considering described diffuse pattern of radiotracer uptake and our findings, inflammatory origin could be a possible reason. Another biodistribution study of 68 Ga-PSMA found occasional nodal uptake in axillary lymph nodes 32 . PSMA tracer positivity in lymph nodes may present serious pitfall as a mimic of metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…Aberrant expression of PSMA in thyroid carcinoma may have a potential to widen therapeutic options in the management of RAI-refractory thyroid cancer. A study of a large cohort of thyroid tumors would be desirable to further elucidate these issues and potentially advocate the use of PSMA-based imaging in thyroid patients 32 .…”

Section: Introductionmentioning

confidence: 99%

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PSMA expression by microvasculature of thyroid tumors – Potential implications for PSMA theranostics

Bychkov

Vutrapongwatana

Tepmongkol

et al. 2017

Sci Rep

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Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer epithelium, making it a promising target for molecular imaging and therapy. Recently, several studies found unexpected PSMA radiotracer uptake by thyroid tumors, including radioiodine-refractory (RAIR) cancers. PSMA expression was reported in tumor-associated endothelium of various malignancies, however it has not been systematically addressed in thyroid tumors. We found that PSMA was frequently expressed in microvessels of thyroid tumors (120/267), but not in benign thyroid tissue. PSMA expression in neovasculature was highly irregular ranging from 19% in benign tumors to over 50% in thyroid cancer. Such heterogeneity was not directly attributed to endothelial cell proliferation as confirmed by immunostaining with proliferation-associated endothelial marker CD105. PSMA expression was associated with tumor size (p = 0.02) and vascular invasion in follicular carcinoma (p = 0.03), but not with other baseline histological, and clinical parameters. Significant translational implication is that RAIR tumors and high-grade cancers maintain high level of PSMA expression, and can be targeted by PSMA ligand radiopharmaceuticals. Our study predicts several pitfalls potentially associated with PSMA imaging of the thyroid, such as low expression in oncocytic tumors, absence of organ specificity, and PSMA-positivity in dendritic cells of chronic thyroiditis, which is described for the first time.Prostate specific membrane antigen (PSMA) is a type II transmembrane glycoprotein highly restricted to prostate epithelium 1, 2 . It is also known as FOLH1 (folate hydrolase 1) or glutamate carboxypeptidase II. Immunohistochemical studies reported that PSMA is strongly expressed by normal and neoplastic prostatic epithelium, along with the epithelium of other genitourinary organs (bladder, kidney, fallopian tubes) and intestine [3][4][5] . Several recent studies found that PSMA could be expressed not only by epithelial cells, but also by vascular endothelium of various malignancies including oral 6 , gastric and colorectal 7 , lung 8 , breast 9 , endometrial and ovarian 10 , renal 11 , urothelial 12 , and glial tumors 13,14 .PSMA is an integral membrane protein, anchored to the epithelial cells. This makes an important advantage of being a targeting marker over prostate-related secretory antigens released into bloodstream, such as prostate specific antigen, prostatic acid phosphatase and prostate secretory protein 15 . Molecular imaging of PSMA is now being widely adopted in prostate cancer diagnostics [16][17][18] . 68 Ga-PSMA PET/CT is a novel imaging modality based on 68 Ga conjugated with anti-PSMA monoclonal antibody, which is highly accurate in detecting prostate cancer 19 . It also has promising therapeutic potential, being a carrier for radionuclides directed against cancer cells. One of such theranostic example is 177 Lu-labelled tracer PSMA-DKFZ-617, which demonstrated radiological response in preclinical model and clinical studies of prostate canc...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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PSMA expression by microvasculature of thyroid tumors – Potential implications for PSMA theranostics

Bychkov

Vutrapongwatana

Tepmongkol

et al. 2017

Sci Rep

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“…11 Overall, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) are higher for 68 Ga-PSMA PET. 7,8 The findings in our case were in keeping with persistent localised disease within the unresected seminal vesicles. Because the initial surgery was limited by anatomic distortion, biopsy of the suspicious area or re-resection was not possible.…”

supporting

confidence: 85%

68Gallium-prostate-specific membrane antigen ligand positron-emission tomography or computed tomography in biochemical failure after radical prostatectomy: A case report

Chidothe

Anderson

2017

S. Afr. j. oncol.

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Biochemical failure after radical treatment for prostate cancer occurs in up to 30% – 50% of cases. Localisation of clinical disease is challenging because clinical symptoms often manifest long after the initial rise in prostate-specific antigen. The detection rates of imaging modalities such as contrasted computed tomography (CT), bone scan, magnetic resonance imaging and choline positron-emission tomography (PET) or CT, are limited. Prostate-specific membrane antigen (PSMA) ligand PET or CT is a novel imaging modality under investigation for various diagnostic and therapeutic indications in the management of prostate cancer. We present a case report illustrating how <sup><span style="font-size: small;">68</span></sup>Gallium-PSMA ligand PET or CT was used to guide management in a patient presenting with biochemical failure after radical prostatectomy.

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“…Trotz des Namens wurde eine physiologische Expression dieses onkologischen Targets auch in anderen Organen (z. B. im proximalen Nierentubulus, im Duodenum und v. a. in den Kopfspeicheldrüsen [62]) als auch bei weiteren Tumorentitäten (u. a. Nierenzellkarzinom) und in der Neovaskularisierung verschiedenster Malignome nachgewiesen [63]. Die genaue Genese der Überexpression dieser Folathydrolase I oder Glutamatcarboxypeptidase II auf entdifferenzierten Prostatakarzinomzellen bleibt ungeklärt, die inzwischen sehr umfangreichen klinischen Resultate zeigen jedoch, dass es sich ideal zur Theranostik eignet [64,65].…”

Section: Psma-vermittelte Radioligandentherapieunclassified

Molekulare Radiotherapie mit neuen Radiopharmaka: Präzisionsonkologie zur personalisierten Patientenbehandlung

et al. 2018

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ZusammenfassungMaligne Erkrankungen sind mit Veränderungen auf der molekularen Ebene assoziiert. Präzisionsonkologie meint einen personalisierten Therapieansatz, der auf spezifische molekulare Signale in Tumorzellen abzielt und mit optimaler Wirksamkeit bei minimalen Nebenwirkungen verbunden ist. Tumore können hochwirksam mit Radiopharmaka behandelt werden, die auf spezifische, zelluläre Mechanismen abzielen (z. B. Metastasen von gut differenzierten neuroendokrinen Neoplasmen mittels 177Lu markierten Somatostatinanaloga). Die molekulare Bildgebung mit PET/CT oder PET/MRT spielt eine entscheidende Rolle bei der Patientenauswahl sowie bei der Überwachung des Therapieansprechens und ist daher in der Lage, die molekulare Radiotherapie zu steuern („wir sehen, was wir behandeln“ und umgekehrt). Theranostik in der Nuklearmedizin fügt sich daher in die Definition der Präzisionsonkologie ein, da sie beispielhaft die Kombination von molekularer Bildgebung und molekularer Radiotherapie beinhaltet, wobei derselbe Vektor, markiert mit unterschiedlichen Radionukliden, zum einen für die Diagnose und zum anderen für die Behandlung verwendet wird. Während die Anwendung von 131I durch Saul Hertz Mitte des letzten Jahrhunderts erstmals den Weg für eine gezielte molekulare Radiotherapie eröffnete, fasst dieser Übersichtsartikel die Therapie mit in den letzten Jahren neuentwickelten Radiopharmaka zusammen.

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Normal distribution pattern and physiological variants of 68Ga-PSMA-11 PET/CT imaging

Abstract: This study shows normal distribution pattern, range of SUVs, and physiological variants of Ga-PSMA-11. In addition, several potential pitfalls were documented to prevent misinterpretations of the scan.

Cited by 131 publications

References 21 publications

PSMA expression by microvasculature of thyroid tumors – Potential implications for PSMA theranostics

PSMA expression by microvasculature of thyroid tumors – Potential implications for PSMA theranostics

68Gallium-prostate-specific membrane antigen ligand positron-emission tomography or computed tomography in biochemical failure after radical prostatectomy: A case report

Molekulare Radiotherapie mit neuen Radiopharmaka: Präzisionsonkologie zur personalisierten Patientenbehandlung

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