tbuckley/cabot-search huggingface dataset:
Radiosensitizing Favors Response to Peptide Receptor Radionuclide Therapy in Patients With Highly Proliferative Neuroendocrine Malignancies
Authors: Nils Florian Trautwein, Clemens Hinterleitner, Lena Sophie Kiefer, Stephan Singer, Sven Mattern, Johannes Schwenck, Gerald Reischl, Bence Sipos, Ulrich M. Lauer, Helmut Dittmann, Lars Zender, Christian la Fougère, Martina Hinterleitner
Journal: Clinical Nuclear Medicine (2024)

Abstract Aim/Introduction Peptide receptor radionuclide therapy (PRRT) represents a cornerstone of treatment regimens for patients with low proliferative neuroendocrine tumors (NETs). However, in patients experiencing somatostatin receptor–positive NET with higher proliferation rates, a value and potential therapeutic benefit of PRRT as part of multimodal treatment approaches and potentially with addition of radiosensitizing agents has not yet been established. Patients and Methods In this study, 20 patients with histologically confirmed gastroenteropancreatic (GEP) NET with proliferation rates (Ki67) between 15% and 55% were treated either with PRRT only (n = 10) or with a combination therapy (n = 10) comprising PRRT and capecitabine/temozolomide (CAP/TEM) for at least 2 consecutive cycles. Results Disease control rate in patients treated with PRRT alone was 60% (40% stable disease and 20% partial response). Strikingly, in patients treated with PRRT in combination with radiosensitization (CAP/TEM), the disease control rate was 90% (20% stable disease and 70% partial response). The median progression-free survival in the PRRT only group was 12 months, whereas the median progression-free survival in the PRRT + CAP/TEM group was 26 months and has not been yet reached for all patients in the group during the observation period. The median disease-specific survival for patients with PRRT alone was 51 months, whereas this end point was not yet reached in the PRRT + CAP/TEM group. Moreover, the PRRT + CAP/TEM group showed a significantly higher reduction of SSTR-PET–based metabolic tumor volume and chromogranin A levels compared with the PRRT only group. Importantly, adverse events of all grades did not differ between both groups. Conclusions PRRT + CAP/TEM represents a highly promising and well-tolerated therapeutic regimen for patients experiencing somatostatin receptor–positive NET with higher (Ki67 ≥ 15%) proliferation rate. Prospective randomized clinical trials are warranted.
Comparison of Recombinant Human Thyroid-Stimulating Hormone and Thyroid Hormone Withdrawal for 131I Therapy in Patients With Intermediate- to High-Risk Thyroid Cancer
Authors: Sohyun Park, Ji-In Bang, Keunyoung Kim, Youngduk Seo, Ari Chong, Chae Moon Hong, Dong-Eun Lee, Miyoung Choi, Sang-Woo Lee, So Won Oh
Journal: Clinical Nuclear Medicine (2024)

Background This meta-analysis and systematic review aimed to evaluate the therapeutic efficacy and advantages associated with the use of recombinant human thyroid-stimulating hormone (rhTSH) for radioactive iodine (RAI) therapy in patients with intermediate- to high-risk differentiated thyroid cancer. Patients and Methods MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant articles reporting clinical outcomes of rhTSH compared with thyroid hormone withdrawal (THW) in patients with intermediate- to high-risk differentiated thyroid cancer published between January 2012 and June 2023. Meta-analyses were performed (PROSPERO registration number: CRD42022340915) to assess the success rate of radioiodine remnant ablation (RRA) in patients with intermediate to high risk and determine the disease control rate among patients with distant metastases, evaluated using the RECIST criteria. Results Thirteen studies involving 1858 patients were included in the meta-analysis. Pooled analyses revealed significantly higher overall RRA success rate in the rhTSH group compared with the THW group, with a risk ratio (RR) of 1.12 (95% confidence interval [CI], 1.01–1.25). However, in the subgroup analysis of high-risk patients, pooled analyses showed no significant differences in RRA success rate between the rhTSH group compared with the THW group with a pooled RR of 1.05 (95% CI, 0.88–1.24). In patients with distant metastases, there were no significant differences in the disease control rate between groups, with a pooled RR of 1.06 (95% CI, 0.78–1.44). Conclusions rhTSH for RAI therapy is a practical option for RAI therapy in patients with intermediate- to high-risk thyroid cancer, including those with distant metastases.
Intracranial Phosphaturic Mesenchymal Tumor Detected by 68Ga-DOTATATE PET/CT
Authors: Qinwen Shi, Junjun Cheng, Yue Zhang, Minggang Su
Journal: Clinical Nuclear Medicine (2024)

Abstract A 68 Ga-DOTATATE PET/CT scan was conducted to locate the causative tumor responsible for suspected tumor-induced osteomalacia in a 56-year-old woman. The PET/CT images showed a focus in the right occipital region. Subsequent MRI showed an extra-axial nodule in the right occipital region, mimicking a meningioma. Although rare, an intracranial phosphaturic mesenchymal tumor was still suspected because of the typical clinical settings. Finally, phosphaturic mesenchymal tumor was confirmed by the postoperative pathology.
Gallbladder’s Adenocarcinoma With Enteroblastic Differentiation Revealed by 18F-FDG PET/CT
Authors: Yan Cui, Yi Liu, Bulin Du, Yaming Li, Xuena Li
Journal: Clinical Nuclear Medicine (2024)

Abstract Gallbladder’s adenocarcinoma with enteroblastic differentiation (GAED) is extremely rare. A 43-year-old woman complained of pain in the right upper abdomen, and enhanced CT showed a cystic and solid mixed mass in the hepatic hilar region. Adenocarcinoma with enteroblastic differentiation was pathologically identified. 18 F-FDG PET/CT revealed a lesion in the gallbladder neck with increased FDG uptake, accompanied by a cystic and solid mixed mass in the hepatic hilar region with liver and lymph node metastases. Gallbladder biopsy was also carried out, and GAED was confirmed. 18 F-FDG PET/CT may assist in the evaluation of GAED and guide biopsy.
18F-FAPI-04 PET/CT in a Case of Primary Gastric Plasmacytoma
Authors: Yiyuan Dong, Tingting Zhao, Liqiong Ma, Aisheng Dong, Qian Zhao
Journal: Clinical Nuclear Medicine (2024)

Primary plasmacytoma of the stomach is very rare. We describe contrast-enhanced CT and 18 F-FAPI-04 PET/CT findings in a patient with primary gastric plasmacytoma and Helicobacter pylori infection. The gastric tumor appeared as a large hypervascular polypoid mass on contrast-enhanced CT and showed intense 18 F-FAPI-04 uptake with SUV max of 11.8 on 18 F-FAPI-04 PET/CT.
Ecto-CD38-NADase inhibition modulates cardiac metabolism and protects mice against doxorubicin-induced cardiotoxicity
Authors: Thais R Peclat, Guillermo Agorrody, Laura Colman, Sonu Kashyap, Julianna D Zeidler, Claudia C S Chini, Gina M Warner, Katie L Thompson, Pranjali Dalvi, Felipe Beckedorff, Sanam Ebtehaj, Joerg Herrmann, Wim van Schooten, Eduardo Nunes Chini
Journal: Cardiovascular Research (2024)

Abstract Aims Doxorubicin (DXR) is a chemotherapeutic agent that causes dose-dependent cardiotoxicity. Recently, it has been proposed that the NADase CD38 may play a role in doxorubicin-induced cardiotoxicity (DIC). CD38 is the main NAD+-catabolizing enzyme in mammalian tissues. Interestingly, in the heart, CD38 is mostly expressed as an ecto-enzyme that can be targeted by specific inhibitory antibodies. The goal of the present study is to characterize the role of CD38 ecto-enzymatic activity in cardiac metabolism and the development of DIC. Methods and results Using both a transgenic animal model and a non-cytotoxic enzymatic anti-CD38 antibody, we investigated the role of CD38 and its ecto-NADase activity in DIC in pre-clinical models. First, we observed that DIC was prevented in the CD38 catalytically inactive (CD38-CI) transgenic mice. Both left ventricular systolic function and exercise capacity were decreased in wild-type but not in CD38-CI mice treated with DXR. Second, blocking CD38-NADase activity with the specific antibody 68 (Ab68) likewise protected mice against DIC and decreased DXR-related mortality by 50%. A reduction of DXR-induced mitochondrial dysfunction, energy deficiency, and inflammation gene expression were identified as the main mechanisms mediating the protective effects. Conclusion NAD+-preserving strategies by inactivation of CD38 via a genetic or a pharmacological-based approach improve cardiac energetics and reduce cardiac inflammation and dysfunction otherwise seen in an acute DXR cardiotoxicity model.
Hypermetabolic Axillary Lymphadenopathy After Shingrix Vaccination for Varicella Zoster Virus
Authors: Yael Eshet, Michal Eifer, Liran Domachevsky, Noam Tau
Journal: Clinical Nuclear Medicine (2024)

Abstract A 67-year-old woman underwent staging 18 F-FDG PET/CT scan for recently diagnosed breast cancer. Her scan showed a highly hypermetabolic right breast mass, with ipsilateral hypermetabolic axillary lymph nodes. The contralateral axillary lymph nodes were also enlarged with avid FDG uptake, alongside focal increased uptake in the left deltoid muscle. Upon investigation, the patient reported receiving the new zoster recombinant adjuvanted varicella zoster vaccine (Shingrix, GlaxoSmithKline) 4 days before the scan. The lymph node uptake could be potential pitfall for cancer staging.
Cryoablation triggers type I interferon-dependent antitumor immunity and potentiates immunotherapy efficacy in lung cancer
Authors: Chuanjia Gu, Xue Wang, Kaiyu Wang, Fangfang Xie, Luonan Chen, Hongbin Ji, Jiayuan Sun
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Cryoablation is a minimally invasive option for patients with medically inoperable non-small cell lung cancer (NSCLC) and can trigger abscopal immune-regulatory effects. However, it remains unclear how cryoablation affects the host-level immune response in NSCLC. In this study, we investigated the local and systemic immunological effects of cryoablation and the potential of combining cryoablation with programmed cell death protein 1 (PD-1) blockade to boost immunotherapy efficacy in NSCLC. Methods We first investigated systemic immunological effects induced by cryoablation in patients with early-stage NSCLC. Subsequently, we explored cryoablation-induced antitumor immunity and the underlying biological mechanisms using KP ( Kras G12D/+ , Tp53 −/− ) mutant lung cancer cell allograft mouse models. Moreover, the synergistic efficacy of cryoablation and PD-1 blockade was explored in both mouse models and patients with unresectable NSCLC. Results We found that cryoablation significantly increased circulating CD8 + T cell subpopulations and proinflammatory cytokines in patients with early-stage NSCLC. In lung cancer cell allograft mouse models, we demonstrated that cryoablation resulted in abscopal growth inhibition of contralateral, non-ablated tumors. Integrated analysis of bulk, single-cell RNA and T cell receptor (TCR) sequencing data revealed that cryoablation reprogrammed the intratumoral immune microenvironment and increased CD8 + T cell infiltration with higher effector signature, interferon (IFN) response, and cytolytic activity. Mechanistically, cryoablation promoted antitumor effect through the STING-dependent type I IFN signaling pathway, and type I IFN signaling blockade attenuated this antitumor effect. We also found that the combination of PD-1 blockade with cryoablation further inhibited tumor growth compared with either treatment alone in an allograft mouse model. Moreover, the combination therapy induced notable tumor suppression and CD8 + T cell infiltration in patients with unresectable NSCLC. Conclusions Our results provide mechanistic insights into how cryoablation triggers the antitumor immune effect in lung cancer, thereby potentiating programmed cell death ligand 1 (PD-L1)/PD-1 blockade efficacy in the clinical treatment of NSCLC.
Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders
Authors: Brandon M Huffman, Harshabad Singh, Lestat R Ali, Nora Horick, S Jennifer Wang, Megan T Hoffman, Katherine A Metayer, Shayla Murray, Alexandra Bird, Thomas A Abrams, Leah H Biller, Jennifer A Chan, Jeffrey A Meyerhardt, Nadine J McCleary, Wolfram Goessling, Anuj K Patel, Jeffrey S Wisch, Matthew B Yurgelun, Kent Mouw, Brendan Reardon, Eliezer M Van Allen, Jessica A Zerillo, Jeffrey W Clark, Aparna Parikh, Robert J Mayer, Benjamin Schlechter, Kimmie Ng, Sunil Kumar, Catherine Del Vecchio Fitz, Charlotte Kuperwasser, Glenn J Hanna, Andrew L Coveler, Douglas A Rubinson, Emma L Welsh, Kathleen Pfaff, Scott Rodig, Stephanie K Dougan, James M Cleary
Journal: Journal for ImmunoTherapy of Cancer (2024)

Recent trials suggest that programmed cell death 1 (PD-1)-directed immunotherapy may be beneficial for some patients with anal squamous cell carcinoma and biomarkers predictive of response are greatly needed. This multicenter phase II clinical trial (NCT02919969) enrolled patients with metastatic or locally advanced incurable anal squamous cell carcinoma (n=32). Patients received pembrolizumab 200 mg every 3 weeks. The primary endpoint of the trial was objective response rate (ORR). Exploratory objectives included analysis of potential predictive biomarkers including assessment of tumor-associated immune cell populations with multichannel immunofluorescence and analysis of circulating tumor tissue modified viral-human papillomavirus DNA (TTMV-HPV DNA) using serially collected blood samples. To characterize the clinical features of long-term responders, we combined data from our prospective trial with a retrospective cohort of patients with anal cancer treated with anti-PD-1 immunotherapy (n=18). In the phase II study, the ORR to pembrolizumab monotherapy was 9.4% and the median progression-free survival was 2.2 months. Despite the high level of HPV positivity observed with circulating TTMV-HPV DNA testing, the majority of patients had low levels of tumor-associated CD8+PD-1+ T cells on pretreatment biopsy. Patients who benefited from pembrolizumab had decreasing TTMV-HPV DNA scores and a complete responder's TTMV-HPV DNA became undetectable. Long-term pembrolizumab responses were observed in one patient from the trial (5.3 years) and three patients (2.5, 6, and 8 years) from the retrospective cohort. Long-term responders had HPV-positive tumors, lacked liver metastases, and achieved a radiological complete response. Pembrolizumab has durable efficacy in a rare subset of anal cancers. However, despite persistence of HPV infection, indicated by circulating HPV DNA, most advanced anal cancers have low numbers of tumor-associated CD8+PD-1+ T cells and are resistant to pembrolizumab.
Inhibiting PLA2G7 reverses the immunosuppressive function of intratumoral macrophages and augments immunotherapy response in hepatocellular carcinoma
Authors: Feng Zhang, Wenfeng Liu, Fansheng Meng, Qiuyu Jiang, Wenqing Tang, Zhiyong Liu, Xiahui Lin, Ruyi Xue, Si Zhang, Ling Dong
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Hepatocellular carcinoma (HCC) is an exceptionally immunosuppressive malignancy characterized by limited treatment options and a dismal prognosis. Macrophages constitute the primary and heterogeneous immune cell population within the HCC microenvironment. Our objective is to identify distinct subsets of macrophages implicated in the progression of HCC and their resistance to immunotherapy. Methods Intratumoral macrophage-specific marker genes were identified via single-cell RNA sequencing analyses. The clinical relevance of phospholipase A2 Group VII (PLA2G7), a pivotal enzyme in phospholipid metabolism, was assessed in patients with HCC through immunohistochemistry and immunofluorescence. Flow cytometry and an in vitro co-culture system were used to elucidate the specific role of PLA2G7 in macrophages. Orthotopic and subcutaneous HCC mouse models were employed to evaluate the potential of the PLA2G7 inhibitor in complementing immune checkpoint blockade (ICB) therapy. Results Single-cell RNA sequencing analyses disclosed predominant PLA2G7 expression in intratumoral macrophages within the HCC microenvironment. The macrophage-specific PLA2G7 was significantly correlated with poorer prognosis and immunotherapy resistance in patients with HCC. PLA2G7 high macrophages represent a highly immunosuppressive subset and impede CD8 T-cell activation. Pharmacological inhibition of PLA2G7 by darapladib improved the therapeutic efficacy of anti-programmed cell death protein 1 antibodies in the HCC mouse models. Conclusions Macrophage-specific PLA2G7 serves as a novel biomarker capable of prognosticating immunotherapy responsiveness and inhibiting PLA2G7 has the potential to enhance the efficacy of ICB therapy for HCC.
Urinary Endometriosis Misdiagnosed as Ureteral Malignant Tumor by PET/CT
Authors: Hao-Yu Zhu, You Cheng, Si-Yun Wang, Dan Shao
Journal: Clinical Nuclear Medicine (2024)

Abstract Endometriosis is a chronic inflammatory estrogen-dependent benign disease. It is defined as the endometrium growing outside the uterine cavity and the myometrium. It usually has low FDG uptake but rarely occurs in the ureters. We reported a case of a 47-year-old woman’s left ureteral nodule originally misdiagnosed as a ureteral malignant tumor by PET/CT and finally pathologically confirmed as endometriosis.
Cerebral and Muscular Metastases From Prostate Adenocarcinoma Initially Depicted by 177Lu-PSMA SPECT/CT
Authors: Akram Al-Ibraheem, Feras Istatieh, Ahmed Saad Abdlkadir, Mohammed Shahait, Fadi Khreish
Journal: Clinical Nuclear Medicine (2024)

Abstract Cerebral and muscular metastases from prostatic adenocarcinoma occur rarely. Patients who develop such metastatic pattern exhibit noticeable symptoms. Herein, we present a 68-year-old man diagnosed with metastatic castrate-resistant prostate cancer. The patient received multiple 177 Lu-PSMA cycles. After the last cycle, a posttreatment SPECT/CT suggested disease progression with uncommon metastatic pattern in the right temporal brain lobe and muscles. 68 Ga-PSMA PET/CT and brain MRI confirmed these findings. Surprisingly, the patient remained asymptomatic up until the conclusion of the follow-up, which lasted for 3 months. This case emphasizes the importance of posttreatment scintigraphic imaging when other biomarkers are inconclusive.
18F-FDG PET/CT Findings of Ovarian Myxoid Chondrosarcoma
Authors: Lei Ou, Yue Zhou, Hao Deng, XiaoLiang Chen
Journal: Clinical Nuclear Medicine (2024)

Abstract Ovarian myxoid chondrosarcoma is a rare and aggressive tumor. We present 18 F-FDG PET/CT findings of ovarian myxoid chondrosarcoma. The images not only demonstrated a pelvic mass with increased FDG uptake, but also a mass with increased FDG uptake in the right lower abdominal wall. Ovarian malignancy with abdominal wall metastases was suspected. An extraskeletal myxoid chondrosarcoma was diagnosed histopathologically after the mass excision.
Contribution of 68Ga-DOTA-FAPI-04 PET/CT to Prostate Cancer Imaging
Authors: Nurhan Ergül, Tevfik Fikret Çermik, Göksel Alçın, Esra Arslan, Özge Erol Fenercioğlu, Ediz Beyhan, Rahime Şahin, Mehmnet Can Baloğlu, Sevim Baykal Koca, Rüştü Türkay, Uğur Yücetaş
Journal: Clinical Nuclear Medicine (2024)

Purpose Prostate-specific membrane antigen (PSMA)–targeted PET/CT is a well-established imaging method in prostate cancer (PC) for both staging and restaging, and also for theranostic applications. An alternative imaging method is crucial for 15% PSMA-negative cases. We aimed to investigate the contribution of 68 Ga-DOTA-FAPI-04 PET/CT to PC imaging. Patients and Methods Thirty-six patients diagnosed with PC were included. Patients underwent both 68 Ga-PSMA PET/CT and 68 Ga-DOTA-FAPI-04 PET/CT imaging within 1 week. In staging group, primary tumor uptake values were compared, and also correlations were done with histopathological findings, MRI findings, and total PSA levels. In biochemical recurrence group, the uptake values in prostatic region and metastases were evaluated to define the local recurrence or metastatic disease. Results In staging group, PSMA PET showed increased uptake in the primary lesion area in 14/27 (52%) patients, whereas 20/27 (74%) patients were positive in FAPI-04 PET. FAPI-04 positivity was found to be quite high, such as 54%, in PSMA-negative patients. A significant difference was observed between ISUP grade 1–3 patients and ISUP grade 4–5 patients in FAPI-04 PET ( P = 0.03). Local recurrence was detected in 3 patients, pelvic lymph node metastasis in 1 patient, and sacrum metastasis in 1 patient in biochemical recurrence group, and all of the lesions had more intense uptake in PSMA PET than FAPI-04 PET. Conclusions FAPI PET imaging seems to have a potential to contribute PSMA PET imaging with FAPI positivity in more than half of PSMA-negative cases. Also, FAPI-targeted radionuclide therapy may be a promising method in patients resistant to PSMA-targeted therapy.
Comparison of the 68Ga-FAPI Versus 18F-FDG in Gastric Adenocarcinoma and Anthracosis-Associated Lymph Nodes: FAPI Unmasking False-Negatives and False-Positives
Authors: Gündüzalp Buğrahan Babacan, Müge Öner Tamam, Selma Şengiz Erhan, Mehmet Can Şahin, Merve Nur Acar Tayyar
Journal: Clinical Nuclear Medicine (2024)

Abstract A 73-year-old woman with poorly differentiated gastric adenocarcinoma was referred to 18 F-FDG PET/CT for evaluation of the disease. FDG PET/CT showed intense uptake in the disseminated lymph nodes. However, there was no uptake in the primary tumoral lesion. Subsequently, 68 Ga-FAPI-04 PET/CT was performed with the decision of the tumor board and demonstrated intense uptake in the tumoral lesion. However, there was low or no uptake in disseminated lymph nodes. Tru-cut biopsy results revealed that all the lymph nodes were associated with anthracosis.
FAPI PET Missed Widespread Bone Marrow Metastases From Follicular Thyroid Cancer That Were Detected by FDG PET
Authors: Xuan Shi, Wei Lan, Ji Bin
Journal: Clinical Nuclear Medicine (2024)

Abstract A 62-year-old woman with follicular thyroid cancer who had received total thyroidectomy and multiple rounds of radioactive iodine therapy underwent both 18 F-FDG and 18 F-FAPI PET/CT. 18 F-FAPI PET failed to reveal widespread bone marrow metastases that were clear visualized on 18 F-FDG PET. This case highlights that FAPI PET may not be used to describe bone metastases in detail in follicular thyroid cancer patients, as it is not a sensitive method to detect bone marrow metastases.
Metastatic Renal Cell Carcinoma in a Patient With Autosomal Dominant Polycystic Kidney Disease
Authors: Wyatt M. Rumrill, David H. Ballard
Journal: Clinical Nuclear Medicine (2024)

Abstract Autosomal dominant polycystic kidney disease (ADPKD) manifests as multiple cysts in the kidneys and liver but can also present with musculoskeletal and cardiovascular abnormalities. ADPKD patients are at increased risk for renal cell carcinoma development. We show the FDG PET/CT findings in a patient with renal cell carcinoma secondary to ADPKD and complicated by worsening pulmonary metastasis. The primary renal tumor shows intense FDG uptake despite no suspicious features with contrast CT.
Comparison of 18F-FDG and 18F-FAPI PET/CT Findings of Signet-Ring Cell Carcinoma of the Stomach
Authors: Meixin Zhao, Annan Zhang, Ming Zu, Yanpeng Ma, Shigang Ding, Weifang Zhang
Journal: Clinical Nuclear Medicine (2024)

Abstract A 66-year-old man with gastric signet-ring cell carcinoma underwent both 18 F-FDG and 18 FAl-NOTA-FAPI PET/CT imaging. There was no abnormal FDG activity in the stomach, but there was diffuse intense 18 FAl-NOTA-FAPI uptake in the known lesion and an adjacent metastasis.
18F-FDG PET/CT Findings, Monkeypox, and HIV Patient
Authors: Hinpetch Daungsupawong, Viroj Wiwanitkit
Journal: Clinical Nuclear Medicine (2024)

Private Academic Consultancy, Phonhong, Lao People's Democratic Republic [email protected] Chandigarh University, Chandigarh, India Hinpetch Daungsupawong ORCID: 0009-0002-5881-2709 Viroj Wiwanitkit ORCID 0000-0003-1039-3728 Author Contributions: H.D.: 50% ideas, writing, analyzing, and approval. V.W.: 50% ideas, supervision, and approval. Conflicts of interest and sources of funding: none declared.