Unusual Uptake of Prostate Specific Tracer 68Ga-PSMA–HBED-CC in a Benign Thyroid Nodule

Damle, Nishikant; Tripathi, Madhavi; Chakraborty, Partha Sarathi; Sahoo, Manoranjan; Bal, Chandrasekhar; Sk, Aggarwal; Arora, Geetanjali; Kumar, Praveen; Kumar, Rajeev; Gupta, Rekha

doi:10.1007/s13139-016-0408-y

Cited by 21 publications

(19 citation statements)

References 15 publications

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“…Several consecutive case reports described 68 Ga-PSMA-positive thyroid tumors, including adenoma 23–25 and carcinoma 26–28 . Many of these tumors were detected incidentally in patients screened for prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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

Bychkov

Vutrapongwatana

Tepmongkol

et al. 2017

Sci Rep

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“…However, high 68 Ga-PSMA expression has also been described in malignant lesions not related to the prostate (e.g., renal cell carcinoma, bronchial carcinoma, glioblastoma), in benign tissues (e.g., renal tubules, duodenum, colon), and in benign lesions such as schwannomas, osteophytes, thyroid adenomas or vertebral and subcutaneous hemangiomas (1,(6)(7)(8)(9)(10)(11)(12)(13)(14). The ganglia of the sympathetic trunk are another tissue in which an increased 68 Ga-PSMA expression has been reported (15,16).…”

mentioning

confidence: 99%

⁶⁸Ga-PSMA-HBED-CC Uptake in Cervical, Celiac, and Sacral Ganglia as an Important Pitfall in Prostate Cancer PET Imaging

et al. 2018

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The study aims to investigate the presence of physiologic prostate-specific membrane antigen (Ga-PSMA)-ligand uptake on PET in cervical, celiac, and sacral ganglia of the sympathetic trunk as a pitfall for lymph node metastases in prostate cancer imaging. Four hundred seven patients who underwent Glu-NH-CO-NH-Lys radiolabeled withGa-gallium -bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine--diacetic acid (Ga-PSMA-HBED-CC) PET (combined with a diagnostic CT) were retrospectively analyzed. The number of Ga-PSMA PET-positive cervical, celiac, and sacral ganglia was determined, and the configuration and SUV of each ganglion were measured. In addition, the configuration and SUV of adjacent lymph node metastases in the respective region (cervical, celiac, or sacral) were determined. Ga-PSMA-ligand uptake above background was detected in 401 (98.5%) patients in any peripheral ganglia, in 369 (92%) patients in cervical ganglia, in 363 (89%) patients in celiac ganglia, and in 183 (46%) patients in sacral ganglia. TheGa-PSMA-ligand uptake was highest in celiac (mean SUV, 2.9 ± 0.8 vs. cervical mean SUV, 2.4 ± 0.6) and sacral (mean SUV 1.7 ± 0.5; both < 0.0001) ganglia. Intraindividually there was a statistically significant but weak to moderate correlation between the Ga-PSMA-ligand uptake in cervical versus celiac ganglia ( = 0.34, < 0.0001), cervical versus sacral ( = 0.52, < 0.0001), and celiac versus sacral ( = 0.16, < 0.05). The Ga-PSMA-ligand uptake was significantly more intense in adjacent lymph node metastases than the respective ganglia (cervical: 18.0 ± 16.2 vs. 2.4 ± 0.6, < 0.0001; celiac: 13.5 ± 12.3 vs. 2.9 ± 0.8, < 0.0001; sacral: 13.4 ± 11.6 vs. 1.7 ± 0.5, < 0.0001). Furthermore, ganglia predominantly exhibit a band-shaped configuration (71.2%), followed by a teardrop (26.8%) and only rarely a nodular configuration (2.0%). Conversely, lymph node metastases are only rarely band-shaped (1.1%), but more often show teardrop (40.3%) or nodular appearance (58.6%) ( < 0.00001). Ga-PSMA-ligand uptake in ganglia along the sympathetic trunk as assessed byGa-PSMA-HBED-CC PET represents an important pitfall in prostate cancer PET imaging. The Ga-PSMA-ligand uptake is higher in celiac ganglia than cervical or sacral ganglia, and the level ofGa-PSMA-ligand uptake seems to be patient-related. For the differentiation between lymph node metastases and sympathetic ganglia, both intensity of Ga-PSMA-ligand uptake and exact localization and configuration of the respective lesion should be examined carefully.

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“…[22][23][24][25][26] For example, in a report by Kanthan et al [23] a known case of prostate cancer underwent […”

Section: Discussionmentioning

confidence: 99%

“…[22][23][24][25][26] This study is conducted to evaluate the expression of PSMA by Immunohistochemistry in neovasculature of thyroid follicular neoplasms to determine its usefulness for distinguishing between adenoma and carcinoma. Also, to evaluate the potential capability of radio labeled Anti PSMA antibody as complementary target therapy in advanced thyroid malignancies.…”

Section: A-542mentioning

confidence: 99%

Expression of PSMA in Thyroid follicular neoplasms: Utility for differentiating between benign from malignant lesions

Saffar

kiany

Tavangar

et al. 2017

APALM

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Background: Prostate-Specific Membrane Antigen (PSMA) has been known as a tumor associated neovasculature marker in some solid malignant tumors. Targeting of PSMA by cytotoxic-conjugated antibody can represent powerful tool for vascular targeted therapy. In thyroid, it appears that angiogenesis factors are involved in neoplastic growth and aggressiveness of tumors.This study was conducted to evaluate the expression of PSMA as an angiogenesis factor in neovasculature of thyroid follicular neoplasms by immunohistochemistry to determine its usefulness for distinguishing between adenoma and carcinoma.Methods: Paraffin Blocks of formalin fixed samples representing 48 cases of Follicular Thyroid Adenoma (FTA) and 15 cases of Follicular Thyroid Carcinoma (FTC) were evaluated.Results: Among 15 cases of FTC, 11 cases revealed both capsular and vascular invasion. In one case only capsular and in two cases only vascular invasions were observed. One case also revealed suspicious vascular invasion with further bone metastasis.The intensity of PSMA staining in vascular structures of carcinomas were significantly higher in comparison with thyroid follicular adenomas (p=0.028). However, we observed no significant difference in the extent of PSMA expression in adenoma and carcinoma groups (p=0.239).Thyroid follicular cells were negative for PSMA in adenoma, carcinoma and in non-neoplastic area. Conclusion:According to our findings, significant higher intensity of PSMA expression in FTC could be useful in differentiating between FTA and FTC. However, more importantly, expression in neovasculature of differentiated thyroid tumors can represent a potential utility for PSMA-targeted radionuclide therapy in advanced differentiated thyroid cancers.

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Unusual Uptake of Prostate Specific Tracer 68Ga-PSMA–HBED-CC in a Benign Thyroid Nodule

Cited by 21 publications

References 15 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

⁶⁸Ga-PSMA-HBED-CC Uptake in Cervical, Celiac, and Sacral Ganglia as an Important Pitfall in Prostate Cancer PET Imaging

Expression of PSMA in Thyroid follicular neoplasms: Utility for differentiating between benign from malignant lesions

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Unusual Uptake of Prostate Specific Tracer 68Ga-PSMA–HBED-CC in a Benign Thyroid Nodule

Cited by 21 publications

References 15 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

68Ga-PSMA-HBED-CC Uptake in Cervical, Celiac, and Sacral Ganglia as an Important Pitfall in Prostate Cancer PET Imaging

Expression of PSMA in Thyroid follicular neoplasms: Utility for differentiating between benign from malignant lesions

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⁶⁸Ga-PSMA-HBED-CC Uptake in Cervical, Celiac, and Sacral Ganglia as an Important Pitfall in Prostate Cancer PET Imaging