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12 pages, 543 KiB

Open AccessArticle

Performances of Functional and Anatomic Imaging Modalities in Succinate Dehydrogenase A-Related Metastatic Pheochromocytoma and Paraganglioma

by Mayank Patel, Abhishek Jha, Alexander Ling, Clara C. Chen, Corina Millo, Mickey J. M. Kuo, Matthew A. Nazari, Sara Talvacchio, Kailah Charles, Markku Miettinen, Jaydira Del Rivero, Alice P. Chen, Naris Nilubol, Frank I. Lin, Ali Cahid Civelek, David Taïeb, Jorge A. Carrasquillo and Karel Pacak

Cancers 2022, 14(16), 3886; https://doi.org/10.3390/cancers14163886 - 11 Aug 2022

Cited by 7 | Viewed by 1862

Abstract

The study identifies the importance of positron emission tomographic (PET) and anatomic imaging modalities and their individual performances in detecting succinate dehydrogenase A (SDHA)-related metastatic pheochromocytoma and paraganglioma (PPGL). The detection rates of PET modalities—⁶⁸Ga-DOTATATE, ¹⁸F-FDG, and ¹⁸ [...] Read more.

The study identifies the importance of positron emission tomographic (PET) and anatomic imaging modalities and their individual performances in detecting succinate dehydrogenase A (SDHA)-related metastatic pheochromocytoma and paraganglioma (PPGL). The detection rates of PET modalities—⁶⁸Ga-DOTATATE, ¹⁸F-FDG, and ¹⁸F-FDOPA—along with the combination of computed tomography (CT) and magnetic resonance imaging (MRI) are compared in a cohort of 11 patients with metastatic PPGL in the setting of a germline SDHA mutation. The imaging detection performances were evaluated at three levels: overall lesions, anatomic regions, and a patient-by-patient basis. ⁶⁸Ga-DOTATATE PET demonstrated a lesion-based detection rate of 88.6% [95% confidence interval (CI), 84.3–92.5%], while ¹⁸F-FDG, ¹⁸F-FDOPA, and CT/MRI showed detection rates of 82.9% (CI, 78.0–87.1%), 39.8% (CI, 30.2–50.2%), and 58.2% (CI, 52.0–64.1%), respectively. The study found that ⁶⁸Ga-DOTATATE best detects lesions in a subset of patients with SDHA-related metastatic PPGL. However, ¹⁸F-FDG did detect more lesions in the liver, mediastinum, and abdomen/pelvis anatomic regions, showing the importance of a combined approach using both PET modalities in evaluating SDHA-related PPGL. Full article

(This article belongs to the Special Issue Molecular Imaging and Radio-Nuclide Therapy in Cancers)

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16 pages, 544 KiB

Open AccessArticle

Comparison of [¹⁸F]PSMA-1007 with [⁶⁸Ga]Ga-PSMA-11 PET/CT in Restaging of Prostate Cancer Patients with PSA Relapse

by Manuela A. Hoffmann, Finn Edler von Eyben, Nicolas Fischer, Florian Rosar, Jonas Müller-Hübenthal, Hans-Georg Buchholz, Helmut J. Wieler and Mathias Schreckenberger

Cancers 2022, 14(6), 1479; https://doi.org/10.3390/cancers14061479 - 14 Mar 2022

Cited by 19 | Viewed by 4214

Abstract

This study aimed to compare the diagnostic performance of [¹⁸F]PSMA-1007 positron emission tomography/computed tomography (PET/CT) (¹⁸F-PSMA) and [⁶⁸Ga]Ga-PSMA-11 PET/CT (⁶⁸Ga-PSMA) by identifying prostate-specific antigen (PSA) threshold levels for optimal detecting recurrent prostate cancer (PC) and [...] Read more.

This study aimed to compare the diagnostic performance of [¹⁸F]PSMA-1007 positron emission tomography/computed tomography (PET/CT) (¹⁸F-PSMA) and [⁶⁸Ga]Ga-PSMA-11 PET/CT (⁶⁸Ga-PSMA) by identifying prostate-specific antigen (PSA) threshold levels for optimal detecting recurrent prostate cancer (PC) and to compare both methods. Retrospectively, the study included 264 patients. The performances of ¹⁸F-PSMA and ⁶⁸Ga-PSMA in relation to the pre-scan PSA were assessed by receiver operating characteristic (ROC) curve. ¹⁸F-PSMA showed PC-lesions in 87.5% (112/128 patients), while ⁶⁸Ga-PSMA identified them in 88.9% (121/136). For ¹⁸F-PSMA biochemical recurrent (BCR) patients treated with radical prostatectomy (78/128, patient group: F-RP), a PSA of 1.08 ng/mL was found to be the optimal cut-off level for predicting positive and negative scans (AUC = 0.821; 95%, CI: 0.710–0.932), while for prostatectomized ⁶⁸Ga-PSMA BCR-patients (89/136, patient group: Ga-RP), the cut-off was 1.84 ng/mL (AUC = 0.588; 95%, CI: 0.410–0.766). In patients with PSA < 1.08 ng/mL (F-RP) 76.3% and <1.84 ng/mL (Ga-RP) 78.6% scans were positive, whereas patients with PSA ≥ 1.08 ng/mL (F-RP) or 1.84 ng/mL (Ga-RP) had positive scan results in 100% and 91.5% (p < 0.001/p = 0.085). The identified PSA thresholds for PSMA-mappable PC lesions in BCR-patients (RP) showed a better separation for ¹⁸F-PSMA with regard to the distinguishing of positive and negative PC-lesions compared to ⁶⁸Ga-PSMA. However, the two PSMA PET/CT tracers gave similar overall findings. Full article

(This article belongs to the Special Issue Molecular Imaging and Radio-Nuclide Therapy in Cancers)

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18 pages, 2324 KiB

Open AccessArticle

Targeted Alpha-Particle Radiotherapy and Immune Checkpoint Inhibitors Induces Cooperative Inhibition on Tumor Growth of Malignant Melanoma

by Mengshi Li, Dijie Liu, Dongyoul Lee, Yinwen Cheng, Nicholas J. Baumhover, Brenna M. Marks, Edwin A. Sagastume, Zuhair K. Ballas, Frances L. Johnson, Zachary S. Morris and Michael K. Schultz

Cancers 2021, 13(15), 3676; https://doi.org/10.3390/cancers13153676 - 22 Jul 2021

Cited by 19 | Viewed by 6125

Abstract

Radiotherapy can facilitate the immune recognition of immunologically “cold” tumors and enhance the efficacy of anti-PD-1 and anti-CTLA-4 immune checkpoint inhibitors (ICIs) in melanoma. Systemic administration of receptor-targeted radionuclide therapy has the potential to selectively deliver radionuclides to multiple tumors throughout the body [...] Read more.

Radiotherapy can facilitate the immune recognition of immunologically “cold” tumors and enhance the efficacy of anti-PD-1 and anti-CTLA-4 immune checkpoint inhibitors (ICIs) in melanoma. Systemic administration of receptor-targeted radionuclide therapy has the potential to selectively deliver radionuclides to multiple tumors throughout the body in metastatic settings. By triggering immunologic cell death and increasing the immune susceptibility of surviving tumor cells in these locations, targeted radionuclide therapies may overcome resistance to ICIs and render immunologically “cold” tumors throughout the body responsive to ICIs and immunologically “hot”. Here, we show the anti-tumor cooperation of targeted α-particle radionuclide therapy (α-TRT) and ICIs in preclinical models of melanoma. Melanocortin 1 receptor (MC1R)-targeted radiopeptide [²¹²Pb]VMT01 was employed to deliver α-radiation to melanoma tumors in mice. A single injection of 4.1 MBq [²¹²Pb]VMT01 significantly slowed the tumor growth of B16-F10 melanoma and the combination of [²¹²Pb]VMT01 and ICIs induced a cooperative anti-tumor effect leading to 43% complete tumor response with no sign of malignancy on autopsy. Animals with complete response developed anti-tumor immunity to reject further tumor inoculations. This therapeutic cooperation was completely abolished in RAG1 KO mice, which are deficient in T-cell maturation. In addition, the anti-tumor cooperation was compromised when fractionated [²¹²Pb]VMT01 was used in the combination. We also demonstrated that [²¹²Pb]VMT01 induced immunogenic cell death in tumor vaccination assays and in vitro exposure to [²¹²Pb]VMT01 sensitized immunotolerant melanoma to ICIs treatment in vivo. Enhanced tumor infiltrating CD3⁺, CD4⁺, CD8⁺ lymphocytes were observed following injection of 1.4 MBq [²¹²Pb]VMT01. Overall, we demonstrated anti-tumor cooperation between α-TRT and ICIs in melanoma that is mediated by tumor specific immunity. Full article

(This article belongs to the Special Issue Molecular Imaging and Radio-Nuclide Therapy in Cancers)

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10 pages, 1840 KiB

Open AccessArticle

Renal Safety of [¹⁷⁷Lu]Lu-PSMA-617 Radioligand Therapy in Patients with Compromised Baseline Kidney Function

by Florian Rosar, Niklas Kochems, Mark Bartholomä, Stephan Maus, Tobias Stemler, Johannes Linxweiler, Fadi Khreish and Samer Ezziddin

Cancers 2021, 13(12), 3095; https://doi.org/10.3390/cancers13123095 - 21 Jun 2021

Cited by 31 | Viewed by 3713

Abstract

Background: Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is an effective antitumor-treatment in metastatic castration-resistant prostate carcinoma (mCRPC). Concerns of potential nephrotoxicity are based on renal tubular PSMA expression and the resulting radiopharmaceutical retention during RLT, but data confirming clinically significant renal [...] Read more.

Background: Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is an effective antitumor-treatment in metastatic castration-resistant prostate carcinoma (mCRPC). Concerns of potential nephrotoxicity are based on renal tubular PSMA expression and the resulting radiopharmaceutical retention during RLT, but data confirming clinically significant renal toxicity are still lacking. In this study, patients with significantly impaired baseline kidney function before initiation of therapy were investigated for treatment-associated nephrotoxicity and the potential relationship with administered activities of [¹⁷⁷Lu]Lu-PSMA-617. Methods: Twenty-two mCRPC patients with impaired renal function (glomerular filtration rate (GFR) ≤ 60 mL/min) who received more than two cycles of [¹⁷⁷Lu]Lu-PSMA-617 RLT (median 5 cycles and median 6-week time interval between consecutive cycles) were analyzed in this study. Patients were treated within a prospective patient registry (REALITY Study, NCT04833517). Cumulative administered activities ranged from 17.1 to 85.6 GBq with a median activity of 6.5 GBq per cycle. Renal function was closely monitored during and after PSMA-RLT. Results: Mean pre-treatment GFR was 45.0 ± 10.7 mL/min. After two (22/22 patients), four (20/22 patients), and six cycles (10/22 patients) of RLT, a significant increase of GFR was noted (each p < 0.05). End-of-treatment GFR (54.1 ± 16.7 mL/min) was significantly higher than baseline GFR (p = 0.016). Only one patient experienced deterioration of renal function (change of CTCAE grade 2 to 3). The remaining patients showed no significant reduction of GFR, including follow-up assessments (6, 9, and 12 months), and even showed improved (10/22 patients) or unchanged (11/22 patients) CTCAE-based renal impairment grades during and after the end of PSMA-RLT. No significant correlation between the change in GFR and per-cycle (p = 0.605) or cumulative (p = 0.132) administered activities were found. Conclusions: As pre-treatment chronic kidney failure did not lead to detectable RLT-induced deterioration of renal function in our study, the nephrotoxic potential of [¹⁷⁷Lu]Lu-PSMA-617 RLT may be overestimated and not of clinical priority in the setting of palliative treatment in mCRPC. We suggest not to categorically exclude patients from enrolment to PSMA-RLT due to renal impairment. Full article

(This article belongs to the Special Issue Molecular Imaging and Radio-Nuclide Therapy in Cancers)

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14 pages, 3008 KiB

Open AccessArticle

PSMA Expression Predicts Early Biochemical Response in Patients with Metastatic Castration-Resistant Prostate Cancer under ¹⁷⁷Lu-PSMA-617 Radioligand Therapy

by Liam Widjaja, Rudolf A. Werner, Tobias L. Ross, Frank M. Bengel and Thorsten Derlin

Cancers 2021, 13(12), 2938; https://doi.org/10.3390/cancers13122938 - 11 Jun 2021

Cited by 21 | Viewed by 3264

Abstract

¹⁷⁷Lu-Prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) is a promising treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to determine the predictive value of pretherapeutic PSMA-ligand positron emission tomography (PET) and established clinical parameters for early biochemical response after [...] Read more.

¹⁷⁷Lu-Prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) is a promising treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to determine the predictive value of pretherapeutic PSMA-ligand positron emission tomography (PET) and established clinical parameters for early biochemical response after two cycles of RLT. In total, 71 mCRPC patients who had undergone PET/computed tomography (CT) with ⁶⁸Ga-PSMA-11 prior to two cycles of ¹⁷⁷Lu-PSMA-617 RLT were included. Malignant lesions on pretherapeutic PET/CTs were manually segmented and average maximum PSMA expression (maximum standardized uptake values, SUV_max), whole-body PSMA-tumor volume (TV), and whole-body total lesion (TL)-PSMA were calculated. We then tested the predictive performance of these parameters for early biochemical response (defined as prostate-sepcific antigen (PSA) decrease of ≥50% according to PCWG2) after two cycles of RLT, relative to established clinical parameters. Early PSA response was observed in 34/71 patients. PSA change after two cycles of RLT correlated with pretherapeutic SUV_max (r = −0.49; p < 0.001), but not with PSMA-TV (r = 0.02; p = 0.89) or TL-PSMA (r = −0.15; p = 0.22). A cut-off of 19.8 for SUV_max and 75.5 years for age was defined by receiver operating characteristics and revealed a significant outcome difference for early biochemical response between patients with adversely low vs. high PSMA expression and low vs. high age (p < 0.001). Multivariate analysis identified SUV_max (HR, 7.94, p = 0.001) and age (HR, 8.05, p = 0.002) as independent predictors for PSA response early in the treatment course. Thus, high age and high PSMA expression in patients scheduled for RLT identify patients with early biochemical response. This study provides a rationale for further prospective studies exploring PET-guided treatment intensification in selected patients. Full article

(This article belongs to the Special Issue Molecular Imaging and Radio-Nuclide Therapy in Cancers)

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20 pages, 3476 KiB

Open AccessArticle

Efficacy of Targeted Radionuclide Therapy Using [¹³¹I]ICF01012 in 3D Pigmented BRAF- and NRAS-Mutant Melanoma Models and In Vivo NRAS-Mutant Melanoma

by Hussein Akil, Mercedes Quintana, Jérémy H. Raymond, Tommy Billoux, Valentin Benboubker, Sophie Besse, Philippe Auzeloux, Véronique Delmas, Valérie Petit, Lionel Larue, Michel D’Incan, Françoise Degoul and Jacques Rouanet

Cancers 2021, 13(6), 1421; https://doi.org/10.3390/cancers13061421 - 20 Mar 2021

Cited by 5 | Viewed by 3081

Abstract

Purpose: To assess the efficiency of targeted radionuclide therapy (TRT), alone or in combination with MEK inhibitors (MEKi), in melanomas harboring constitutive MAPK/ERK activation responsible for tumor radioresistance. Methods: For TRT, we used a melanin radiotracer ([¹³¹I]ICF01012) currently in phase 1 [...] Read more.

Purpose: To assess the efficiency of targeted radionuclide therapy (TRT), alone or in combination with MEK inhibitors (MEKi), in melanomas harboring constitutive MAPK/ERK activation responsible for tumor radioresistance. Methods: For TRT, we used a melanin radiotracer ([¹³¹I]ICF01012) currently in phase 1 clinical trial (NCT03784625). TRT alone or combined with MEKi was evaluated in three-dimensional melanoma spheroid models of human BRAF^V600E SK-MEL-3, murine NRAS^Q61K 1007, and WT B16F10 melanomas. TRT in vivo biodistribution, dosimetry, efficiency, and molecular mechanisms were studied using the C57BL/6J-NRAS^Q61K 1007 syngeneic model. Results: TRT cooperated with MEKi to increase apoptosis in both BRAF- and NRAS-mutant spheroids. NRAS^Q61K spheroids were highly radiosensitive towards [¹³¹I]ICF01012-TRT. In mice bearing NRAS^Q61K 1007 melanoma, [¹³¹I]ICF01012 induced a significant extended survival (92 vs. 44 days, p < 0.0001), associated with a 93-Gy tumor deposit, and reduced lymph-node metastases. Comparative transcriptomic analyses confirmed a decrease in mitosis, proliferation, and metastasis signatures in TRT-treated vs. control tumors and suggest that TRT acts through an increase in oxidation and inflammation and P53 activation. Conclusion: Our data suggest that [¹³¹I]ICF01012-TRT and MEKi combination could be of benefit for advanced pigmented BRAF-mutant melanoma care and that [¹³¹I]ICF01012 alone could constitute a new potential NRAS-mutant melanoma treatment. Full article

(This article belongs to the Special Issue Molecular Imaging and Radio-Nuclide Therapy in Cancers)

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11 pages, 3069 KiB

Open AccessArticle

In Vivo Biodistribution and Efficacy Evaluation of NeoB, a Radiotracer Targeted to GRPR, in Mice Bearing Gastrointestinal Stromal Tumor

by Christopher Montemagno, Florian Raes, Mitra Ahmadi, Sandrine Bacot, Marlène Debiossat, Julien Leenhardt, Jean Boutonnat, Francesca Orlandi, Donato Barbato, Mattia Tedesco, Catherine Ghezzi, Pascale Perret and Alexis Broisat

Cancers 2021, 13(5), 1051; https://doi.org/10.3390/cancers13051051 - 2 Mar 2021

Cited by 14 | Viewed by 3181

Abstract

NeoB is a radiotracer targeting the gastrin-releasing peptide receptor (GRPR), a G-protein–coupled receptor expressed in various cancers. The aim of the present study was to evaluate the biodistribution and efficacy of this new therapeutic agent in Gastrointestinal Stromal Tumors (GIST). Eighty-two SCID mice [...] Read more.

NeoB is a radiotracer targeting the gastrin-releasing peptide receptor (GRPR), a G-protein–coupled receptor expressed in various cancers. The aim of the present study was to evaluate the biodistribution and efficacy of this new therapeutic agent in Gastrointestinal Stromal Tumors (GIST). Eighty-two SCID mice bearing GIST-882 tumors were employed. [¹⁷⁷Lu]Lu-NeoB biodistribution was evaluated up to seven days by organ sampling (200 pmol/0.8 MBq, i.v.). For efficacy evaluation, mice received either saline, 400 pmol or 800 pmol of [¹⁷⁷Lu]Lu-NeoB (37MBq, 1/w, 3 w, i.v.). SPECT/CT imaging was performed at 24 h, and tumor volume was determined up to 100 days. Elevated and specific [¹⁷⁷Lu]Lu-NeoB uptake was found in the GIST tumor, as demonstrated by in vivo competition (19.1 ± 3.9 %ID/g vs. 0.3 ± 0.1 %ID/g at 4h). [¹⁷⁷Lu]Lu-NeoB tumor retention (half-life of 40.2 h) resulted in elevated tumor-to-background ratios. Tumor volumes were significantly reduced in both treated groups (p < 0.01), even leading to complete tumor regression at the 400 pmol dose. [¹⁷⁷Lu]Lu-NeoB exhibited excellent pharmacokinetics with elevated and prolonged tumor uptake and low uptake in non-target organs such as pancreas. The potential of this new theragnostic agent in different indications, including GIST, is under evaluation in the FIH [¹⁷⁷Lu]Lu-NeoB clinical trial. Full article

(This article belongs to the Special Issue Molecular Imaging and Radio-Nuclide Therapy in Cancers)

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Review

Jump to: Research

19 pages, 1757 KiB

Open AccessReview

Clinical Evaluation of Nuclear Imaging Agents in Breast Cancer

by Ziqi Li, Mariam S. Aboian, Xiaohua Zhu and Bernadette Marquez-Nostra

Cancers 2022, 14(9), 2103; https://doi.org/10.3390/cancers14092103 - 23 Apr 2022

Cited by 5 | Viewed by 2546

Abstract

Precision medicine is the customization of therapy for specific groups of patients using genetic or molecular profiling. Noninvasive imaging is one strategy for molecular profiling and is the focus of this review. The combination of imaging and therapy for precision medicine gave rise [...] Read more.

Precision medicine is the customization of therapy for specific groups of patients using genetic or molecular profiling. Noninvasive imaging is one strategy for molecular profiling and is the focus of this review. The combination of imaging and therapy for precision medicine gave rise to the field of theranostics. In breast cancer, the detection and quantification of therapeutic targets can help assess their heterogeneity, especially in metastatic disease, and may help guide clinical decisions for targeted treatments. Positron emission tomography (PET) or single-photon emission tomography (SPECT) imaging has the potential to play an important role in the molecular profiling of therapeutic targets in vivo for the selection of patients who are likely to respond to corresponding targeted therapy. In this review, we discuss the state-of-the-art nuclear imaging agents in clinical research for breast cancer. We reviewed 17 clinical studies on PET or SPECT agents that target 10 different receptors in breast cancer. We also discuss the limitations of the study designs and of the imaging agents in these studies. Finally, we offer our perspective on which imaging agents have the highest potential to be used in clinical practice in the future. Full article

(This article belongs to the Special Issue Molecular Imaging and Radio-Nuclide Therapy in Cancers)

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26 pages, 1952 KiB

Open AccessReview

Radioimmunotherapy in Oncology: Overview of the Last Decade Clinical Trials

by Aurélie Rondon, Jacques Rouanet and Françoise Degoul

Cancers 2021, 13(21), 5570; https://doi.org/10.3390/cancers13215570 - 7 Nov 2021

Cited by 26 | Viewed by 5318

Abstract

The specific irradiation of tumors with selective radiolabeled antibodies constitutes an attractive therapeutic approach. Consequent preclinical research has been conducted by both biologists to identify pertinent targets and to select corresponding antibodies (mAb) and by radiochemists to radiolabel mAbs. These numerous preclinical investigations [...] Read more.

The specific irradiation of tumors with selective radiolabeled antibodies constitutes an attractive therapeutic approach. Consequent preclinical research has been conducted by both biologists to identify pertinent targets and to select corresponding antibodies (mAb) and by radiochemists to radiolabel mAbs. These numerous preclinical investigations have ascertained the therapeutic interest of radioimmunotherapy (RIT) protocols in mice models. Here, we summarize the clinical studies that have been performed the last decade, including clinical trials (phases I, II, and III), prospective and retrospective studies, and cases series. We thereby reported 92 clinical studies. Among them, 62 concern the treatment of hematological malignancies, and 30 concern solid tumors. For hematologic diseases, the analysis was complex due to the high discrepancy of therapeutic strategies (first-line therapy, consolidation, stem cell transplantation conditioning) as well as the high variety of malignancies that were treated. The clinical studies from the last decade failed to expand anti-CD20 RIT indications but confirmed that RIT using radiolabeled anti-CD20 remains a pertinent choice for patients with relapse follicular lymphomas. For solid tumors, the positive benefit of RIT is more mitigated, apart for few malignancies that can be treated locally. Clinical trials also demonstrated the potential of some antibody formats, such as F(ab′)₂, which has already been approved by the China State FDA under the trend name Licartin®. Despite disparate results, mAb fragments are an interesting prospect for the improvement of RIT efficiency as well as for pretargeted strategies that delay the injection of radioactive treatments from the mAb ones. Full article

(This article belongs to the Special Issue Molecular Imaging and Radio-Nuclide Therapy in Cancers)

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17 pages, 1369 KiB

Open AccessReview

FAP and FAPI-PET/CT in Malignant and Non-Malignant Diseases: A Perfect Symbiosis?

by Katharina Dendl, Stefan A. Koerber, Clemens Kratochwil, Jens Cardinale, Rebecca Finck, Mardjan Dabir, Emil Novruzov, Tadashi Watabe, Vasko Kramer, Peter L. Choyke, Uwe Haberkorn and Frederik L. Giesel

Cancers 2021, 13(19), 4946; https://doi.org/10.3390/cancers13194946 - 30 Sep 2021

Cited by 90 | Viewed by 11125

Abstract

A fibroblast activation protein (FAP) is an atypical type II transmembrane serine protease with both endopeptidase and post-proline dipeptidyl peptidase activity. FAP is overexpressed in cancer-associated fibroblasts (CAFs), which are found in most epithelial tumors. CAFs have been implicated in promoting tumor cell [...] Read more.

A fibroblast activation protein (FAP) is an atypical type II transmembrane serine protease with both endopeptidase and post-proline dipeptidyl peptidase activity. FAP is overexpressed in cancer-associated fibroblasts (CAFs), which are found in most epithelial tumors. CAFs have been implicated in promoting tumor cell invasion, angiogenesis and growth and their presence correlates with a poor prognosis. However, FAP can generally be found during the remodeling of the extracellular matrix and therefore can be detected in wound healing and benign diseases. For instance, chronic inflammation, arthritis, fibrosis and ischemic heart tissue after a myocardial infarction are FAP-positive diseases. Therefore, quinoline-based FAP inhibitors (FAPIs) bind with a high affinity not only to tumors but also to a variety of benign pathologic processes. When these inhibitors are radiolabeled with positron emitting radioisotopes, they provide new diagnostic and prognostic tools as well as insights into the role of the microenvironment in a disease. In this respect, they deliver additional information beyond what is afforded by conventional FDG PET scans that typically report on glucose uptake. Thus, FAP ligands are considered to be highly promising novel tracers that offer a new diagnostic and theranostic potential in a variety of diseases. Full article

(This article belongs to the Special Issue Molecular Imaging and Radio-Nuclide Therapy in Cancers)

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29 pages, 1058 KiB

Open AccessReview

PSMA Theranostics: Science and Practice

by Kgomotso Mokoala, Ismaheel Lawal, Thabo Lengana, Mankgopo Kgatle, Frederik L. Giesel, Mariza Vorster and Mike Sathekge

Cancers 2021, 13(15), 3904; https://doi.org/10.3390/cancers13153904 - 2 Aug 2021

Cited by 27 | Viewed by 7226

Abstract

Prostate cancer (PCa) causes significant morbidity and mortality in men globally. While localized PCa may be managed with curative intent by surgery and/or radiation therapy, the management of advanced hormone resistant metastatic disease (mCRPC) is more challenging. Theranostics is a principle based on [...] Read more.

Prostate cancer (PCa) causes significant morbidity and mortality in men globally. While localized PCa may be managed with curative intent by surgery and/or radiation therapy, the management of advanced hormone resistant metastatic disease (mCRPC) is more challenging. Theranostics is a principle based on the ability to use an organ specific ligand and label it to both a diagnostic and a therapeutic agent. The overexpression of prostate specific membrane antigen (PSMA) on prostate cancer cells creates a unique opportunity for development of targeted radionuclide therapy. The use of both beta and alpha emitting particles has shown great success. Several clinical trials have been initiated assessing the efficacy and safety profile of these radionuclide agents. The results are encouraging with PSMA directed radioligand therapy performing well in patients who have exhausted all other standard treatment options. Future studies need to assess the timing of introduction of these radionuclide therapies in the management schema of mCRPC. Drugs or therapies are not without side effects and targeted radionuclide therapies presents a new set of toxicities including xerostomia and myelosuppression. New therapeutic strategies are being explored to improve outcomes while keeping toxicities to a minimum. This review aims to look at the various PSMA labelled tracers that form part of the theragnostic approach and subsequently delve into the progress made in the area of radionuclide therapy. Full article

(This article belongs to the Special Issue Molecular Imaging and Radio-Nuclide Therapy in Cancers)

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13 pages, 1605 KiB

Open AccessReview

Lutetium-177 Labelled PSMA Targeted Therapy in Advanced Prostate Cancer: Current Status and Future Perspectives

by Konstantin Egon Seitzer, Robert Seifert, Katharina Kessel, Wolfgang Roll, Katrin Schlack, Martin Boegemann and Kambiz Rahbar

Cancers 2021, 13(15), 3715; https://doi.org/10.3390/cancers13153715 - 23 Jul 2021

Cited by 15 | Viewed by 4820

Abstract

Patients suffering from metastatic castration-resistant prostate cancer (mCRPC) have a poor prognosis. As a further treatment option ¹⁷⁷Lutetium (Lu) prostate-specific membrane antigen (PSMA) radioligand therapy gained a significant interest of many investigators. Several publications showed great response and prolonged survival with limited [...] Read more.

Patients suffering from metastatic castration-resistant prostate cancer (mCRPC) have a poor prognosis. As a further treatment option ¹⁷⁷Lutetium (Lu) prostate-specific membrane antigen (PSMA) radioligand therapy gained a significant interest of many investigators. Several publications showed great response and prolonged survival with limited adverse events. However, to this point, it still remains unclear which patients benefit the most from ¹⁷⁷Lu-PSMA therapy, and how to improve the treatment regimen to achieve best outcome while minimizing potential adverse events. The efficacy for mCRPC patients is a given fact, and with the newly published results of the VISION trial its approval is only a matter of time. Recently, investigators started to focus on treating prostate cancer patients in earlier disease stages and in combination with other compounds. This review gives a brief overview of the current state and the future perspectives of ¹⁷⁷Lu labelled PSMA radioligand therapy. Full article

(This article belongs to the Special Issue Molecular Imaging and Radio-Nuclide Therapy in Cancers)

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11 pages, 644 KiB

Open AccessReview

Positron Emission Tomography Imaging of Macrophages in Cancer

by Candace C. Parker and Suzanne E. Lapi

Cancers 2021, 13(8), 1921; https://doi.org/10.3390/cancers13081921 - 16 Apr 2021

Cited by 14 | Viewed by 2878

Abstract

Macrophages are large phagocytic cells that can be classified as a type of white blood cell and may be either mobile or stationary in tissues. The presence of macrophages in essentially every major disease makes them attractive candidates to serve as therapeutic targets [...] Read more.

Macrophages are large phagocytic cells that can be classified as a type of white blood cell and may be either mobile or stationary in tissues. The presence of macrophages in essentially every major disease makes them attractive candidates to serve as therapeutic targets and diagnostic biomarkers. Macrophages that are found in the microenvironment of solid tumors are referred to as tumor-associated macrophages (TAMs) and have been shown to influence chemoresistance, immune regulation, tumor initiation and tumor growth. The imaging of TAMs through Positron Emission Tomography (PET) has the potential to provide valuable information on cancer biology, tumor progression, and response to therapy. This review will highlight the versatility of macrophage imaging in cancer through the use of PET. Full article

(This article belongs to the Special Issue Molecular Imaging and Radio-Nuclide Therapy in Cancers)

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