Imaging of Neuroendocrine Prostatic Carcinoma

Taher, Ahmed; Jensen, Corey T.; Yedururi, Sireesha; Surasi, Devaki Shilpa; Faria, Silvana C.; Bathala, Tharakeshwar K; Mujtaba, Bilal; Bhosale, Priya; Wagner‐Bartak, Nicolaus A.; Morani, Ajaykumar C.

doi:10.3390/cancers13225765

Cited by 12 publications

(12 citation statements)

References 81 publications

(95 reference statements)

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“…Despite the great impact and evolution that PSMA has had, there are clinical reports that suggest that PSMA-targeted imaging does not visualize NEPC tumours. Studies have demonstrated that AR regulate the expression of FOLH1, which is the gene responsible for encoding the transmembrane protein prostate-specific membrane antigen; also, the induction of lineage plasticity by AR inhibition leads to neuroendocrine differentiation and PSMA suppression [ 22 , 23 ]. In our study 18 F–PSMA–1007 PET/ CT detected a significant number of lesions, especially bone metastases, with an even better detection rate than 18 F–FDG PET/ CT at these specific sites, which could be possibly explained by the identification of mixed histologic subtypes.…”

Section: Discussionmentioning

confidence: 99%

Multitarget Molecular Imaging in Metastatic Castration Resistant Adenocarcinoma Prostate Cancer with Therapy Induced Neuroendocrine Differentiation

et al. 2022

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Neuroendocrine differentiation of prostate cancer (NEDPC) includes de novo presentation and secondary to epigenetic changes, referred as therapy-induced neuroendocrine prostate cancer (t-NEPC). Molecular imaging with prostate-specific membrane antigen (PSMA) and somatostatin analogues positron emission tomography (PET/CT) in NEDPC have not been validated. 18F-FDG (fluorodeoxyglucose) PET/CT has numerous limitations in prostate cancer (PCa) and the utility in NEDPC has only been reported in a few series of cases. The objective of this study is to compare the lesions detection rate of the three radiotracers in metastatic t-NEPC patients. (1) Material and Methods: Retrospective evaluation of patients with prostate adenocarcinoma treated with androgen deprivation therapy, chemotherapy, a novel androgen receptor pathway inhibitor or a combination of them and a second tumour biopsy confirming t-NEPC was made. All patients underwent 18F PSMA-1007, 18F AlF-NOTA-Octreotide, and 18F-FDG PET/CT. Evaluation of positive lesions was determined and SUVmax of each radiotracer was estimated and correlated with computer tomography (CT) findings. (2) Results: A total of eight patients were included. The mean time from diagnosis of prostate adenocarcinoma to t-NEPC was 28.2 months, with a mean serum specific prostate antigen (PSA) of 16.6 ng/dl at the time of NEPC diagnosis. All patients were treated with antiandrogen therapy and 87.5% with chemotherapy. A total of 273 lesions were identified by CT from which 182 were detected by 18F-FDG PET/CT, 174 lesions by 18F PSMA-1007, and 59 by 18F AlF-NOTA-Octreotide. An interpatient analysis of the lesions was performed and dual tracer 18F-FDG PET/CT and 18F PSMA-1007 PET/CT detected a total of 270/273 lesions (98.9%). (3) Conclusions: NEDPC patients demonstrated wide inter and intrapatient molecular imaging heterogeneity within the three radiotracers. 18F-FDG detected most lesions in t-NEPC among all radiotracers, especially in visceral sites; 18F PSMA-1007 detected more bone lesions. 18F AlF-NOTA-Octreotide showed no significant utility.

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Section: Discussionmentioning

confidence: 99%

Multitarget Molecular Imaging in Metastatic Castration Resistant Adenocarcinoma Prostate Cancer with Therapy Induced Neuroendocrine Differentiation

et al. 2022

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“…The only role of CT is to show an irregularly enlarged prostate and for nodal staging. CT plays a primary role in metastatic staging for detection and restaging of bone and lung metastases in these cases ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

“…While mpMRI is now considered the technique of choice for initial and local (T) tumor staging, PET/CT and PET/MRI have shown great value in distant extraprostatic (N and M) staging. mpMRI can also differentiate prostatic carcinoid from the usual prostatic adenocarcinoma based on the considerably larger size and mild hyperintensity of the tumor on T2W images ( 18 ). Recently, biopsy guided by the fusion of MRI and transrectal ultrasound images (called MRI-TRUS fusion biopsy) is increasingly used where MRI findings are used as a reference for US-guided biopsy, allowing for increased accuracy and precision which is frequently done in our center and in this patient as well ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

A rare case of prostate neuroendocrine tumor: A case report

et al. 2022

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Small cell prostate neuroendocrine carcinoma (SCPC) is a rare and highly aggressive malignant tumor. We present a case of a 52-year-old Iranian man, presenting with complaints of occasional gross hematuria and perineal pain for 6 months. PSA was 0.8 ng/ml. A digital rectal examination found a huge and hard prostate mass. He underwent a transrectal ultrasound-guided (TRUS) biopsy of the prostate. Histopathology showed high-grade small cell neuroendocrine carcinoma. Immunohistochemical markers were positive for synaptophysin with a Ki67 index of almost 100%. However, CD56 and chromogranin A markers were negative. Magnetic resonance imaging (MRI) of the prostate showed a prostate mass with invasion to the rectum, while contrast-enhanced computed tomography of the thorax, abdomen, and pelvis (CT TAP) ruled out metastasis. A multidisciplinary team discussion was carried out, and a decision was made for concurrent chemotherapy and radiation (cisplatin and etoposide for 4 cycles and 70 Gy, 35 fractions). There is a lack of consensus on the management of SCPC. The main modality of management in advanced (stage IV) disease is chemotherapy. It is a highly aggressive tumor with a poor prognosis and is not responsive to hormonal therapy.

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“…A lethal disease with median survival of less than 1 year from the time of detection, neuroendocrine prostate cancer (NEPC) accounts for approximately 25% of all therapy- and castration-resistant prostate cancer (tCRPC) [ 1 , 2 ]. Since prostatic adenocarcinoma (ADPC) is a typical androgen-dependent (AD) cancer, androgen deprivation therapy is the standard of care for this disease.…”

Section: Introductionmentioning

confidence: 99%

“…To date, several lines of studies have reported upregulated levels of SSTR2 expression in NEPC [ 30 ]. For instance, the expression level of SSTR2 was found to be elevated following hormone depletion therapy [ 22 ], and high uptake of 68 Ga-DOTATATE was observed in biochemically relapsed prostate cancer [ 1 , 31 ]. Most recently, targeting of SSTR2 was reported as a practical strategy to develop a polymeric nanoparticle system for NEPC therapy [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

A Theranostic Small-Molecule Prodrug Conjugate for Neuroendocrine Prostate Cancer

et al. 2023

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After androgen deprivation therapy, a significant number of prostate cancer cases progress with a therapy-resistant neuroendocrine phenotype (NEPC). This represents a challenge for diagnosis and treatment. Based on our previously reported design of theranostic small-molecule prodrug conjugates (T-SMPDCs), herein we report a T-SMPDC tailored for targeted positron emission tomography (PET) imaging and chemotherapy of NEPC. The T-SMPDC is built upon a triazine core (TZ) to present three functionalities: (1) a chelating moiety (DOTA: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) for PET imaging when labeled with 68Ga (t1/2 = 68 min) or other relevant radiometals; (2) an octreotide (Octr) that targets the somatostatin receptor 2 (SSTR2), which is overexpressed in the innervated tumor microenvironment (TME); and (3) fingolimod, FTY720—an antagonist of sphingosine kinase 1 that is an intracellular enzyme upregulated in NEPC. Polyethylene glycol (PEG) chains were incorporated via conventional conjugation methods or a click chemistry reaction forming a 1,4-disubstituted 1,2,3-triazole (Trz) linkage for the optimization of in vivo kinetics as necessary. The T-SMPDC, DOTA-PEG3-TZ(PEG4-Octr)-PEG2-Trz-PEG3-Val-Cit-pABOC-FTY720 (PEGn: PEG with n repeating ethyleneoxy units (n = 2, 3, or 4); Val: valine; Cit: citrulline; pABOC: p-amino-benzyloxycarbonyl), showed selective SSTR2 binding and mediated internalization of the molecule in SSTR2 high cells. Release of FTY720 was observed when the T-SMPDC was exposed to cathepsin B, and the released FTY720 exerted cytotoxicity in cells. In vivo PET imaging showed significantly higher accumulation (2.1 ± 0.3 %ID/g; p = 0.02) of [68Ga]Ga-DOTA-PEG3-TZ(PEG4-Octr)-PEG2-Trz-PEG3-Val-Cit-pABOC-FTY720 in SSTR2high prostate cancer xenografts than in the SSTR2low xenografts (1.5 ± 0.4 %ID/g) at 13 min post-injection (p.i.) with a rapid excretion through the kidneys. Taken together, these proof-of-concept results validate the design concept of the T-SMPDC, which may hold a great potential for targeted diagnosis and therapy of NEPC.

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Imaging of Neuroendocrine Prostatic Carcinoma

Cited by 12 publications

References 81 publications

Multitarget Molecular Imaging in Metastatic Castration Resistant Adenocarcinoma Prostate Cancer with Therapy Induced Neuroendocrine Differentiation

Multitarget Molecular Imaging in Metastatic Castration Resistant Adenocarcinoma Prostate Cancer with Therapy Induced Neuroendocrine Differentiation

A rare case of prostate neuroendocrine tumor: A case report

A Theranostic Small-Molecule Prodrug Conjugate for Neuroendocrine Prostate Cancer

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