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4 pages, 189 KiB

Open AccessEditorial

Theranostics in Oncology—Thriving, Now More than Ever

by Rudolf A. Werner, Takahiro Higuchi, Martin G. Pomper and Steven P. Rowe

Diagnostics 2021, 11(5), 805; https://doi.org/10.3390/diagnostics11050805 - 29 Apr 2021

Cited by 4 | Viewed by 3011

Abstract

Tracing its roots back to the 1940s, theranostics in nuclear oncology has proved successful mainly due to the beneficial effects of image-guided therapeutic concepts for patients afflicted with a variety of different cancers. The majority of these treatments are not only characterized by [...] Read more.

Tracing its roots back to the 1940s, theranostics in nuclear oncology has proved successful mainly due to the beneficial effects of image-guided therapeutic concepts for patients afflicted with a variety of different cancers. The majority of these treatments are not only characterized by substantial prolongation of progression-free and overall survival, but are also generally safe, rendering theranostic agents as an attractive treatment option in various clinical scenarios in oncology. In this Special Issue Novel Theranostic Agents, nine original articles from around the globe provide further evidence on the use of the theranostic concept for neuroendocrine neoplasm (NEN), prostate cancer (PC), meningioma, and neuroblastoma. The investigated diagnostic and therapeutic radiotracers target not only established structures, such as somatostatin receptor, prostate-specific membrane antigen or norepinephrine transporter, but also recently emerging targets such as the C-X-C motif chemokine receptor 4. Moreover, the presented original articles also combine the concept of theranostics with in-depth read-out techniques such as radiomics or novel reconstruction algorithms on pretherapeutic scans, e.g., for outcome prediction. Even 80 years after its initial clinical introduction, theranostics in oncology continues to thrive, now more than ever. Full article

(This article belongs to the Special Issue Novel Theranostic Agents)

Research

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10 pages, 1198 KiB

Open AccessArticle

CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas

by Alexander Weich, Rudolf A. Werner, Andreas K. Buck, Philipp E. Hartrampf, Sebastian E. Serfling, Michael Scheurlen, Hans-Jürgen Wester, Alexander Meining, Stefan Kircher, Takahiro Higuchi, Martin G. Pomper, Steven P. Rowe, Constantin Lapa and Malte Kircher

Diagnostics 2021, 11(4), 605; https://doi.org/10.3390/diagnostics11040605 - 29 Mar 2021

Cited by 28 | Viewed by 3435

Abstract

We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer ⁶⁸Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard ¹⁸F-FDG PET/computed tomography (CT). In our [...] Read more.

We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer ⁶⁸Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard ¹⁸F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent ¹⁸F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. ⁶⁸Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while¹⁸F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, ¹⁸F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher ¹⁸F-FDG uptake as compared to ⁶⁸Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUV_max: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUV_mean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard ¹⁸F-FDG PET/CT. Full article

(This article belongs to the Special Issue Novel Theranostic Agents)

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14 pages, 1716 KiB

Open AccessArticle

Correlation of an Index-Lesion-Based SPECT Dosimetry Method with Mean Tumor Dose and Clinical Outcome after ¹⁷⁷Lu-PSMA-617 Radioligand Therapy

by Friederike Völter, Lena Mittlmeier, Astrid Gosewisch, Julia Brosch-Lenz, Franz Josef Gildehaus, Mathias Johannes Zacherl, Leonie Beyer, Christian G. Stief, Adrien Holzgreve, Johannes Rübenthaler, Clemens C. Cyran, Guido Böning, Peter Bartenstein, Andrei Todica and Harun Ilhan

Diagnostics 2021, 11(3), 428; https://doi.org/10.3390/diagnostics11030428 - 3 Mar 2021

Cited by 17 | Viewed by 2706

Abstract

Background: Dosimetry can tailor prostate-specific membrane-antigen-targeted radioligand therapy (PSMA-RLT) for metastatic castration-resistant prostate cancer (mCRPC). However, whole-body tumor dosimetry is challenging in patients with a high tumor burden. We evaluate a simplified index-lesion-based single-photon emission computed tomography (SPECT) dosimetry method in correlation with [...] Read more.

Background: Dosimetry can tailor prostate-specific membrane-antigen-targeted radioligand therapy (PSMA-RLT) for metastatic castration-resistant prostate cancer (mCRPC). However, whole-body tumor dosimetry is challenging in patients with a high tumor burden. We evaluate a simplified index-lesion-based single-photon emission computed tomography (SPECT) dosimetry method in correlation with clinical outcome. Methods: 30 mCRPC patients were included (median 71 years). The dosimetry was performed for the first cycle using quantitative ¹⁷⁷Lu-SPECT. The response was evaluated using RECIST 1.1 and PERCIST criteria, as well as changes in PSMA-positive tumor volume (PSMA-TV) in post-therapy PSMA-PET and biochemical response according to PSA changes after two RLT cycles. Results: Mean tumor doses as well as index-lesion doses were significantly higher in PERCIST responders compared to non-responders (10.2 ± 12.0 Gy/GBq vs. 4.0 ± 2.9 Gy/GBq, p = 0.03 and 13.7 ± 14.2 Gy/GBq vs. 5.9 ± 4.4 Gy/GBq, p = 0.04, respectively). No significant differences in mean tumor and index lesion doses were observed between responders and non-responders according to RECIST 1.1, PSMA-TV, and biochemical response criteria. Conclusion: Compared to mean tumor doses on a patient level, single index-lesion-based SPECT dosimetry correlates equally well with the response to PSMA-RLT according to PERCIST criteria and may represent a fast and feasible dosimetry approach for clinical routine. Full article

(This article belongs to the Special Issue Novel Theranostic Agents)

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13 pages, 1712 KiB

Open AccessArticle

Wnt/β-Catenin Signaling Regulates CXCR4 Expression and [⁶⁸Ga] Pentixafor Internalization in Neuroendocrine Tumor Cells

by Alexander Weich, Dorothee Rogoll, Sophia Gawlas, Lars Mayer, Wolfgang Weich, Judit Pongracz, Theodor Kudlich, Alexander Meining and Michael Scheurlen

Diagnostics 2021, 11(2), 367; https://doi.org/10.3390/diagnostics11020367 - 22 Feb 2021

Cited by 11 | Viewed by 3223

Abstract

Loss of Somatostatin Receptor 2 (SSTR2) expression and rising CXC Chemokine Receptor Type 4 (CXCR4) expression are associated with dedifferentiation in neuroendocrine tumors (NET). In NET, CXCR4 expression is associated with enhanced metastatic and invasive potential and worse prognosis but might be a [...] Read more.

Loss of Somatostatin Receptor 2 (SSTR2) expression and rising CXC Chemokine Receptor Type 4 (CXCR4) expression are associated with dedifferentiation in neuroendocrine tumors (NET). In NET, CXCR4 expression is associated with enhanced metastatic and invasive potential and worse prognosis but might be a theragnostic target. Likewise, activation of Wnt/β-catenin signaling may promote a more aggressive phenotype in NET. We hypothesized an interaction of the Wnt/β-catenin pathway with CXCR4 expression and function in NET. The NET cell lines BON-1, QGP-1, and MS-18 were exposed to Wnt inhibitors (5-aza-CdR, quercetin, and niclosamide) or the Wnt activator LiCl. The expressions of Wnt pathway genes and of CXCR4 were studied by qRT-PCR, Western blot, and immunohistochemistry. The effects of Wnt modulators on uptake of the CXCR4 ligand [⁶⁸Ga] Pentixafor were measured. The Wnt activator LiCl induced upregulation of CXCR4 and Wnt target gene expression. Treatment with the Wnt inhibitors had opposite effects. LiCl significantly increased [⁶⁸Ga] Pentixafor uptake, while treatment with Wnt inhibitors decreased radiopeptide uptake. Wnt pathway modulation influences CXCR4 expression and function in NET cell lines. Wnt modulation might be a tool to enhance the efficacy of CXCR4-directed therapies in NET or to inhibit CXCR4-dependent proliferative signaling. The underlying mechanisms for the interaction of the Wnt pathway with CXCR4 expression and function have yet to be clarified. Full article

(This article belongs to the Special Issue Novel Theranostic Agents)

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10 pages, 2409 KiB

Open AccessArticle

Estimating the Potential of Radiomics Features and Radiomics Signature from Pretherapeutic PSMA-PET-CT Scans and Clinical Data for Prediction of Overall Survival When Treated with ¹⁷⁷Lu-PSMA

by Sobhan Moazemi, Annette Erle, Susanne Lütje, Florian C. Gaertner, Markus Essler and Ralph A. Bundschuh

Diagnostics 2021, 11(2), 186; https://doi.org/10.3390/diagnostics11020186 - 28 Jan 2021

Cited by 39 | Viewed by 3473

Abstract

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PSMA-PET/CT) scans can facilitate diagnosis and treatment of prostate disease. Radiomics signature (RS) is widely used for the analysis of overall survival (OS) in cancer diseases. This study aims at investigating the role of radiomics [...] Read more.

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PSMA-PET/CT) scans can facilitate diagnosis and treatment of prostate disease. Radiomics signature (RS) is widely used for the analysis of overall survival (OS) in cancer diseases. This study aims at investigating the role of radiomics features (RFs) and RS from pretherapeutic gallium-68 (⁶⁸Ga)-PSMA-PET/CT findings and patient-specific clinical parameters to analyze overall survival of prostate cancer (PC) patients when treated with lutethium-177 (¹⁷⁷Lu)-PSMA. A cohort of 83 patients with advanced PC was retrospectively analyzed. Average values of 73 RFs of 2070 malignant hotspots as well as 22 clinical parameters were analyzed for each patient. From the Cox proportional hazard model, the least absolute shrinkage and selection operator (LASSO) regularization method is used to select most relevant features (standardized uptake value (SUV)_Min and kurtosis with the coefficients of 0.984 and −0.118, respectively) and to calculate the RS from the RFs. Kaplan–Meier (KM) estimator was used to analyze the potential of RFs and conventional clinical parameters, such as metabolic tumor volume (MTV) and standardized uptake value (SUV) for the prediction of survival. As a result, SUV_Min, kurtosis, the calculated RS, SUV_Mean, as well as Hemoglobin (Hb)1, C-reactive protein (CRP)1, and ECOG1 (clinical parameters) achieved p-values less than 0.05, which suggest the potential of findings from ⁶⁸Ga-PSMA-PET/CT scans as well as patient-specific clinical parameters for the prediction of OS for patients with advanced PC treated with ¹⁷⁷Lu-PSMA therapy. Full article

(This article belongs to the Special Issue Novel Theranostic Agents)

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11 pages, 5313 KiB

Open AccessArticle

Shortened Tracer Uptake Time in GA-68-DOTATOC-PET of Meningiomas Does Not Impair Diagnostic Accuracy and PET Volume Definition

by Josefine Graef, Carolin Senger, Christoph Wetz, Alexander D. J. Baur, Anne K. Kluge, Mathias Lukas, Julian M. M. Rogasch, Thula C. Walter-Rittel, David Kohnert, Marcus Makowski, Güliz Acker, Kai Huang, Volker Budach, Holger Amthauer, Imke Schatka and Christian Furth

Diagnostics 2020, 10(12), 1084; https://doi.org/10.3390/diagnostics10121084 - 13 Dec 2020

Cited by 3 | Viewed by 3267

Abstract

Ga-68-DOTATOC-PET/MRI can affect the planning target volume (PTV) definition of meningiomas before radiosurgery. A shorter tracer uptake time before image acquisition could allow the examination of more patients. The aim of this study was to investigate if shortening uptake time is possible without [...] Read more.

Ga-68-DOTATOC-PET/MRI can affect the planning target volume (PTV) definition of meningiomas before radiosurgery. A shorter tracer uptake time before image acquisition could allow the examination of more patients. The aim of this study was to investigate if shortening uptake time is possible without compromising diagnostic accuracy and PET volume. Fifteen patients (f = 12; mean age 52 years (34–80 years)) with meningiomas were prospectively examined with dynamic [68Ga]Ga-68-labeled [DOTA0-Phe1-Tyr3] octreotide (Ga-68-DOTATOC)-PET/MRI over 70 min before radiosurgery planning. Meningiomas were delineated manually in the PET dataset. PET volumes at each time point were compared to the reference standard 60 min post tracer injection (p.i.) using the Friedman test followed by a Wilcoxon signed-rank test and Bonferroni correction. In all patients, the earliest time point with 100% lesion detection compared to 60 min p.i. was identified. PET volumes did not change significantly from 15 min p.i. (p = 1.0) compared to 60 min p.i. The earliest time point with 100% lesion detection in all patients was 10 min p.i. In patients with meningiomas undergoing Ga-68-DOTATOC-PET, the tracer uptake time can safely be reduced to 15 min p.i. with comparable PET volume and 100% lesion detection compared to 60 min p.i. Full article

(This article belongs to the Special Issue Novel Theranostic Agents)

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12 pages, 2787 KiB

Open AccessArticle

Asphericity of Somatostatin Receptor Expression in Neuroendocrine Tumors: An Innovative Predictor of Outcome in Everolimus Treatment?

by Christoph Wetz, Julian Rogasch, Philipp Genseke, Imke Schatka, Christian Furth, Michael Kreissl, Henning Jann, Marino Venerito and Holger Amthauer

Diagnostics 2020, 10(9), 732; https://doi.org/10.3390/diagnostics10090732 - 22 Sep 2020

Cited by 8 | Viewed by 2825

Abstract

Background: in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET), the mTOR inhibitor everolimus is associated with significant improvement in progression-free survival (PFS). This study evaluated the lesional asphericity (ASP) in pretherapeutic somatostatin receptor (SSR) imaging as the first imaging-based prognostic marker for PFS. Methods: [...] Read more.

Background: in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET), the mTOR inhibitor everolimus is associated with significant improvement in progression-free survival (PFS). This study evaluated the lesional asphericity (ASP) in pretherapeutic somatostatin receptor (SSR) imaging as the first imaging-based prognostic marker for PFS. Methods: this retrospective bicentric cohort study included 30 patients (f = 13, median age, 66.5 (48–81) years) with pretherapeutic [¹¹¹In-DTPA⁰]octreotide scintigraphy (Octreoscan^®). ASP of functional volumes of up to three leading lesions per patient (n = 74) was calculated after semiautomatic, background-adapted segmentation. Uni- and multivariable Cox regression regarding PFS for clinical factors and the maximum ASP per patient was obtained. Results: all 30 patients showed metachronous or progressive liver metastases. ASP, primary tumor site, metastases pattern, and prior peptide receptor radionuclide therapy (PRRT) were significantly associated with PFS in univariable Cox regression. Only ASP > 12.9% (hazard ratio (HR), 3.33; p = 0.024) and prior PRRT (HR, 0.35; p = 0.043) remained significant in multivariable Cox. Median PFS was 6.7 months for ASP > 12.9% (95% confidence interval (CI), 2.1–11.4 months) versus 14.4 (12.5–16.3) months for ASP ≤ 12.9% (log-rank, p = 0.028). Conclusion: pretherapeutic ASP of SSR positive lesions independently predicted PFS for treatment with everolimus in GEP-NET. ASP may supplement risk-benefit assessment before patient inclusion to treatment. Full article

(This article belongs to the Special Issue Novel Theranostic Agents)

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7 pages, 1157 KiB

Open AccessArticle

Diagnostic Use of Post-therapy ¹³¹I-Meta-Iodobenzylguanidine Scintigraphy in Consolidation Therapy for Children with High-Risk Neuroblastoma

by Hiroshi Wakabayashi, Daiki Kayano, Anri Inaki, Raita Araki, Rie Kuroda, Norihito Akatani, Takafumi Yamase, Satoru Watanabe, Tomo Hiromasa, Yuji Kunita, Hiroshi Mori, Shintaro Saito, Yasuhiro Ikawa, Toshihiro Fujiki and Seigo Kinuya

Diagnostics 2020, 10(9), 663; https://doi.org/10.3390/diagnostics10090663 - 2 Sep 2020

Cited by 7 | Viewed by 3355

Abstract

¹²³I-meta-iodobenzylguanidine (¹²³I-mIBG) scintigraphy is used for evaluating disease extent in children with neuroblastoma. ¹³¹I-mIBG therapy has been used for evaluation in children with high-risk neuroblastoma, and post-therapy ¹³¹I-mIBG scintigraphy may detect more lesions compared with diagnostic ¹²³I-mIBG [...] Read more.

¹²³I-meta-iodobenzylguanidine (¹²³I-mIBG) scintigraphy is used for evaluating disease extent in children with neuroblastoma. ¹³¹I-mIBG therapy has been used for evaluation in children with high-risk neuroblastoma, and post-therapy ¹³¹I-mIBG scintigraphy may detect more lesions compared with diagnostic ¹²³I-mIBG scintigraphy. However, no studies have yet revealed the detection rate of hidden mIBG-avid lesions on post-therapy ¹³¹I-mIBG whole-body scan (WBS) and SPECT images in neuroblastoma children without mIBG-avid lesions as demonstrated by diagnostic ¹²³I-mIBG scintigraphy. We retrospectively examined the diagnostic utility of post-therapy ¹³¹I-mIBG scintigraphy in children who received ¹³¹I-mIBG as consolidation therapy. Nineteen children with complete response to primary therapy were examined. Post-therapy ¹³¹I-mIBG scintigraphy was performed four days after injection. The post-therapy ¹³¹I-mIBG scintigraphy, 4 children exhibited abnormal uptake on the WBS. Post-therapy ¹³¹I-mIBG SPECT/CT provided additional information in 2 cases. In total, 6 children exhibited abnormal uptake. The site of abnormal accumulation was on the recurrence site in one case, operation sites in five cases, and bone metastasis in one case. Post-therapy ¹³¹I-mIBG scintigraphy could detect residual disease that was not recognized using diagnostic ¹²³I-mIBG scintigraphy in 32% of children with high-risk neuroblastoma and ganglioneuroblastoma. The diagnostic use of post-therapy ¹³¹I-mIBG scintigraphy can provide valuable information for detecting residual disease. Full article

(This article belongs to the Special Issue Novel Theranostic Agents)

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