[18F]F-Poly(ADP-Ribose) Polymerase Inhibitor Radiotracers for Imaging PARP Expression and Their Potential Clinical Applications in Oncology.

Including poly(ADP-ribose) polymerase (PARP) inhibitors in managing patients with inoperable tumors has significantly improved outcomes. The PARP inhibitors hamper single-strand deoxyribonucleic acid (DNA) repair by trapping poly(ADP-ribose)polymerase (PARP) at sites of DNA damage, forming a non-functional "PARP enzyme-inhibitor complex" leading to cell cytotoxicity. The effect is more pronounced in the presence of PARP upregulation and homologous recombination (HR) deficiencies such as breast cancer-associated gene (BRCA1/2). Hence, identifying HR-deficiencies by genomic analysis-for instance, BRCA1/2 used in triple-negative breast cancer-should be a part of the selection process for PARP inhibitor therapy. Published data suggest BRCA1/2 germline mutations do not consistently predict favorable responses to PARP inhibitors, suggesting that other factors beyond tumor mutation status may be at play. A variety of factors, including tumor heterogeneity in PARP expression and intrinsic and/or acquired resistance to PARP inhibitors, may be contributing factors. This justifies the use of an additional tool for appropriate patient selection, which is noninvasive, and capable of assessing whole-body in vivo PARP expression and evaluating PARP inhibitor pharmacokinetics as complementary to the currently available BRCA1/2 analysis. In this review, we discuss [18F]Fluorine PARP inhibitor radiotracers and their potential in the imaging of PARP expression and PARP inhibitor pharmacokinetics. To provide context we also briefly discuss possible causes of PARP inhibitor resistance or ineffectiveness. The discussion focuses on TNBC, which is a tumor type where PARP inhibitors are used as part of the standard-of-care treatment strategy.

Incidental Intense Fibroblast Activation Protein Inhibitor (FAPI) Uptake in Bilateral Gluteal Myositis Ossificans: A Case Report.

Positron emission tomography/computed tomography (PET/CT) using 18F-fluorodeoxyglucose ([18F]-FDG) is a widely adopted imaging modality for detecting hypermetabolic lesions. However, emerging positron-emitting tracers, such as radiopharmaceuticals featuring fibroblast activation protein (FAP) inhibitors (FAPI) labeled with [18F] or [68Ga], have opened new avenues in nuclear medicine. This case report focuses on the unique behavior of [68Ga]-FAPI in bilateral gluteal myositis ossificans, an infrequent condition characterized by soft tissue ossification. A 45-year-old woman with gastric adenocarcinoma underwent subtotal gastrectomy and received neoadjuvant and adjuvant chemotherapy; [68Ga]-FAPI PET revealed metastatic processes and unexpected [68Ga]-FAPI avid intramuscular ossifications in the pelvic and bilateral thigh muscles. Even though there was no history of trauma, the patient was diagnosed with myositis ossificans, a condition marked by non-cancerous ectopic ossifications. Diagnosis relies on history, radiology, and/or histology. FAPI imaging, increasingly used for inflammatory and infectious diseases, can exhibit uptake in benign conditions, including those involving bones and joints. This case report is the first to document incidental bilateral [68Ga]-FAPI uptake in bilateral gluteal myositis ossificans. The robust [68Ga]-FAPI activity in myositis ossificans highlights the importance of considering myositis ossificans in the context of soft tissue calcifications with intense [68Ga]-FAPI uptake.

Clinical Characteristics and Outcomes of CML in Adolescents and Young Adults.

BACKGROUND: While Chronic Myeloid Leukemia (CML) is a disease of older adults, there is a growing population of adolescent and young adults (AYAs) with CML. This study evaluated the clinical characteristics and outcomes of CML in AYAs. PATIENTS AND METHODS: Data from medical records of adults with chronic phase CML diagnosed and treated at our center from 2011until 2021were retrospectively analyzed. Age between 18 and 29 years was used to define AYAs. Response to tyrosine kinase inhibitors (TKIs), progression to accelerated phase (AP) or blast crisis (BC), event-free survival (EFS) and overall survival (OS) were compared between AYAs and older adults. RESULTS: Among 163 patients included, 41 (25.1%) were AYAs. AYAs were more likely to be males (P = .02), to present with symptoms (P = .004), had a higher median white blood cell count (P = .007), neutrophil count (P = .029), eosinophil count (P = 0.01), low-risk Sokal (P = .033) and Hasford (P = .005) groups. TKI-sensitivity as well as median times for achievement of complete cytogenetic and major molecular response were comparable between both groups. After a median follow-up of 76 (range: 11-235) months, there was no difference in OS (P = .528), or cumulative incidence of transformation to accelerated phase or blast crisis (P = .11). On the other hand, AYA had an inferior EFS (P = .034). CONCLUSION: A quarter of the patients diagnosed with CML in our population were AYAs. Despite being characterized as "lower-risk," they presented with a greater disease burden, had a shorter EFS but comparable OS. Further studies are needed to better understand the disease biology of this group.

18F-FDG PET/CT Unveils Coexistent Myelomatous Hepatosplenic and Thyroid Cartilage Involvement: A Rare Presentation in Multiple Myeloma.

ABSTRACT: Extramedullary myelomatous disease is an aggressive condition where clonal plasma cells proliferate outside the bone marrow, allowing independent survival. This state is generally associated with negative outcomes. A 65-year-old woman presented with progressive bilateral hypochondrial pain, was initially misattributed to an inflammatory etiology, and was consequently managed with corticosteroid therapy. A bone marrow biopsy was offered after further deterioration confirming plasma cell myeloma. Afterward, 18F-FDG PET/CT revealed medullary and extramedullary hepatosplenic and thyroid cartilage involvement, concluding an overall picture of an atypical and extensive extramedullary myelomatous disease.

From Despair to Hope: First Arabic Experience of 177Lu-PSMA and 161Tb-PSMA Therapy for Metastatic Castration-Resistant Prostate Cancer.

The objective of this retrospective study is to assess the effectiveness and safety of two beta-emitting prostate-specific membrane antigen (PSMA) radioligands, [177Lu]Lu and [161Tb]Tb, in heavily treated patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 148 cycles of beta-emitting PSMA radioligand therapy were given to 53 patients at a specialized cancer care center in Amman, Jordan. This treatment was offered following the exhaustion of all prior treatment modalities. Approximately half of the cases (n = 26) demonstrated an initial partial response to PSMA radioligand therapy. Moreover, roughly one-fourth of the patients (n = 13) exhibited a sustained satisfactory biochemical response, which qualified them to receive a total of six PSMA radioligand therapy cycles and maintain continued follow-up for additional treatment cycles. This was reflected by an adequate prostate-specific antigen (PSA) decline and a concomitant partial response evident on [68Ga]Ga-PSMA positron emission tomography/computed tomography imaging. A minority of patients (n= 18; 34%) experienced side effects. Generally, these were low-grade and self-limiting toxicities. This study endorses previous research evidence about PSMA radioligand therapy's safety and efficacy. It also provides the first clinical insight from patients of Arab ethnicity. This should facilitate and promote further evidence, both regionally and internationally.

Comparative analysis through propensity score matching in thyroid cancer: unveiling the impact of multiple malignancies.

Background: The incidence of thyroid cancer is on the rise worldwide, with childhood exposure to radiation being the sole acknowledged catalyst for its emergence. Nonetheless, numerous other factors that may pose risks are awaiting thorough examination and validation. This retrospective study aims to explore the malignancies linked to thyroid cancer and contrast the survival rates of those afflicted with a solitary tumor versus those with multiple primary neoplasms (MPN). Methods: This retrospective study examined data from King Hussein Cancer Center (KHCC), Jordan. Among 563 patients diagnosed with thyroid cancer, 30 patients had thyroid malignancy as part of MPN. For a 1:3 propensity score-matched analysis, 90 patients with only a primary thyroid malignancy were also enrolled. Results: Hematologic and breast malignancies were among the most frequent observed cancers alongside thyroid neoplasm. Patients who had MPN were diagnosed at older age, had higher body mass index and presented with higher thyroglobulin antibody levels (p < 0.05 for each). Additionally, MPN patient displayed a stronger family history for cancers (p= 0.002). A median follow-up duration of 135 months unveiled that MPN patients faced a worse 5-year survival compared to their counterparts with a singular neoplasm (87% vs 100% respectively; p < 0.01). However, no distinction emerged in the 5-year event-free survival between these two groups. Conclusion: MPN correlates with a significantly altered survival outcome of thyroid cancer patients. The diagnosis of thyroid carcinoma at an older age, accompanied by elevated initial thyroglobulin antibody levels and a notable familial predisposition, may raise concerns about the potential occurrence of synchronous or metachronous tumors.

Navigating The Prostate Cancer Frontier: A Bibliometric and Altmetric Analysis of [225Ac]Ac-PSMA Therapy.

The main aim of this study was to evaluate the current state of bibliometric and altmetric research output of [225Ac]Ac-Prostate specific membrane antigen (PSMA) and its implications for prostate cancer (PC). Both PubMed and Scopus digital libraries were systematically explored to retrieve relevant data on the topic of interest. The study of various bibliometric and altmetric indices was facilitated through the use of Microsoft Excel, Stata (Version 17.0), and VOSviewer (Version 1.6) Softwares. The parameters included in this study comprised the examination of published articles, annual trends, countries, institutions, authors, journals, and co-occurring keywords. From 2014 to 2024, our study examined a total of 100 publications within the given domain. The studies that received the highest citations primarily centered on the crucial topic of metastatic castration-resistant prostate cancer, with a particular emphasis on evaluating the safety and effectiveness of [225Ac]Ac-PSMA therapy. Moreover, much scholarly inquiry has been devoted to examining the [225Ac]Ac-PSMA adverse effects. Three high prolific countries (namely, Germany, United States, and South Africa) dominated the research render in terms of publications and citations. Finally, A strong correlation was observed between altmetric score and citation number (P < 0.001). The observed surge in scholarly research output and altmetric indicators associated with [225Ac]Ac-PSMA signifies a shift in emphasis towards embracing alpha targeted therapy in PC.

False-Negative 68 Ga-FAPI PET/CT in Pediatric Thyroid Medullary Carcinoma Seen With 68 Ga-DOTATOC PET/CT and 18 F-FDG PET/CT.

ABSTRACT: In adults, 68 Ga-FAP inhibitor ( 68 Ga-FAPI) PET/CT outperforms 68 Ga-radiolabeled somatostatin analog peptides ( 68 Ga PET/CT) and 18 F-FDG PET/CT in detecting thyroid lesions. This is the case of a 13-year-old boy newly diagnosed with medullary thyroid cancer with high calcitonin level. 68 Ga PET/CT revealed the presence of only a primary thyroid lesion. Proven to be superior in detecting metastasis, 68 Ga-FAPI PET/CT was performed. The results came out negative for primary and potential metastatic lesions. This case sheds shed light on false-negatives reported in 68 Ga-FAPI PET/CT scans in pediatric patients, emphasizing the need for alternate radiotracers when a negative study is met.

FDG-PET in Chimeric Antigen Receptor T-Cell (CAR T-Cell) Therapy Toxicity: A Systematic Review.

The utilization of chimeric antigen receptor (CAR) T-cell therapy to target cluster of differentiation (CD)19 in cancer immunotherapy has been a recent and significant advancement. Although this approach is highly specific and selective, it is not without complications. Therefore, a systematic review was conducted to assess the current state of positron emission tomography (PET) in evaluating the adverse effects induced by CAR T-cell therapy. A thorough search of relevant articles was performed in databases such as PubMed, Scopus, and Web of Science up until March 2024. Two reviewers independently selected articles and extracted data, which was then organized and categorized using Microsoft Excel. The risk of bias and methodological quality was assessed. In total, 18 articles were examined, involving a total of 753 patients, in this study. A wide range of utilities were analyzed, including predictive, correlative, and diagnostic utilities. While positive outcomes were observed in all the mentioned areas, quantitative analysis of the included studies was hindered by their heterogeneity and use of varying PET-derived parameters. This study offers a pioneering exploration of this promising field, with the goal of encouraging further and more focused research in upcoming clinical trials.

Investigating knowledge of DRLs, image quality and radiation dose in PET/CT and CT imaging among medical imaging professionals.

Objective: To investigate the knowledge of diagnostic reference levels (DRLs), image quality, radiation dose and protocol parameters among Jordanian medical imaging professionals (MIPs) involved in PET/CT and CT scan procedures. Materials and methods: A questionnaire was designed and distributed to MIPs in Jordan. The survey comprised four sections: demographic data, MIP knowledge on dose/protocol parameters, image quality, and DRLs. Statistical analyses were performed utilizing Pearson's correlation, t-tests, ANOVA, and linear regression, with a significance level of 95 % and a p-value threshold of <0.05. Results: The study involved 147 participants. Most respondents were male (76.2 %), and most were aged 26-35 years (44.2 %). Approximately 51 % held a bachelor's degree, and the most common range of experience was 3-5 years (28.6 %). Participants showed a moderate level of knowledge regarding dose and protocol parameters, with a mean score of 61.8 %. The mean scores for knowledge of image quality and DRLs were 45.2 % and 44.8 %, respectively. The age group of the MIPs and the total experience were found to have a significant impact on the knowledge of the dose and protocol parameters, as well as the DRLs. Additionally, experience was found to have a significant influence on knowledge of the dose and protocol parameters. The study revealed a positive and significant effect of MIPs' knowledge of dose/protocol parameters and image quality on their knowledge of DRLs. Conclusions: This study indicates that professionals across five specialties who are engaged in PET/CT and CT imaging possess a moderate understanding of dosage and protocol parameters. However, there is a notable gap in knowledge regarding DRLs and image quality. To address this issue, it is recommended that MIPs actively engage in educational programs emphasizing exposure parameters and their impact on image quality. Additionally, access to comprehensive education and training programs will enable MIPs to grasp the complexities of DRLs and their implications, facilitating their implementation in clinical practice.

PET/CT in leukemia: utility and future directions.

2-Deoxy-2-[ 18 F]fluoro- d -glucose PET/computed tomography ([ 18 F]FDG PET/CT) has proven to be a sensitive method for the detection and evaluation of hematologic malignancies, especially lymphoma. The increasing incidence and mortality rates of leukemia have raised significant concerns. Through the utilization of whole-body imaging, [ 18 F]FDG PET/CT provides a thorough assessment of the entire bone marrow, complementing the limited insights provided by biopsy samples. In this regard, [ 18 F]FDG PET/CT has the ability to assess diverse types of leukemia The utilization of [ 18 F]FDG PET/CT has been found to be effective in evaluating leukemia spread beyond the bone marrow, tracking disease relapse, identifying Richter's transformation, and assessing the inflammatory activity associated with acute graft versus host disease. However, its role in various clinical scenarios in leukemia remains unacknowledged. Despite their less common use, some novel PET/CT radiotracers are being researched for potential use in specific scenarios in leukemia patients. Therefore, the objectives of this review are to provide a thorough assessment of the current applications of [ 18 F]FDG PET/CT in the staging and monitoring of leukemia patients, as well as the potential for an expanding role of PET/CT in leukemia patients.

Gallium-68-Labeled Fibroblast Activation Protein Inhibitor as an Alternative Radiotracer to Fluorine 18-Fluorodeoxyglucose: A Case Report of Rare Pulmonary Colloid Adenocarcinoma Diagnosed by PET/CT.

Colloid pulmonary adenocarcinoma represents a seldom encountered neoplasm in clinical practice. The diagnostic process for this rare neoplasm is complicated by its infrequency and the limited understanding of its specific molecular imaging characteristics. We report a 65-year-old male who was diagnosed with pulmonary colloid mucinous cystadenocarcinoma. Fluorine 18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was conducted for initial evaluation. The scan showed mild 18F-FDG expression at the primary tumor site, and several non-18F-FDG-avid mediastinal and paraesophageal lymph nodes exhibited suspicious morphologic features. Owing to the ongoing atrial fibrillation, initial histopathological confirmation of the primary tumor mass carries a sense of risk, prompting the imperative for cardiological assessment before proceeding. Instead, Gallium-68-labeled fibroblast activation protein inhibitor (68Ga-FAPI) PET/CT was performed, expecting this to be more informative in terms of malignancy potential than 18F-FDG PET in colloid mucinous histology. A scan revealed moderate 68Ga-FAPI expression at the primary tumor site but unremarkable 68Ga-FAPI expression at the questionable lymph node. Subsequently, a biopsy from a mediastinal node (left para-aortic) lymph node via endobronchial ultrasound (EUS) showed benign findings. The patient was treated with concurrent chemoradiation. This case underscores the vital role that 68Ga-FAPI PET/CT can play in specific cases of rare cancers, especially when invasive testing for tissue biopsy is not feasible.

Ocular and Periocular Metastasis in Breast Cancer: Clinical Characteristics, Prognostic Factors and Treatment Outcome.

BACKGROUND: Breast cancer remains a leading cause of cancer-related mortality and morbidity worldwide. Ocular and periocular metastasis present as a rare but clinically significant manifestation. This study aims to explore demographics and clinical aspects of ocular and periocular metastasis in breast cancer patients. METHODS: A retrospective cohort study comprising 45 breast cancer patients with ocular or periocular metastasis treated between 2013 and 2023. Patient demographics, tumor characteristics, diagnostic methods, treatment modalities, visual outcomes, and survival data were analyzed. RESULTS: Among 9902 breast cancer patients, 0.5% developed ocular or periocular metastasis, constituting 2.4% of metastatic cases. The median age was 50 years. Ocular metastasis timing varied: 5% before breast cancer, 24% concurrent, 22% within a year, and 49% after. The most common presentations included incidental MRI findings (42%) and vision decline (31%). Metastasis involved the orbit (47%), choroid (40%), optic nerve (11%), and iris (2%), with 44% having bilateral involvement. Predictive factors included invasive lobular carcinoma (ILC) (p < 0.0001) and brain metastasis (p < 0.0001), with ILC exhibiting a sixfold higher likelihood of ocular metastasis than invasive ductal carcinoma (IDC). Primary treatment was radiation therapy (89%), yielding a 55% maintenance of excellent vision (<0.5), with 93% developing dry eye disease. Patients with ocular metastasis faced an increased risk of disease-related mortality (p < 0.0001), with 71% succumbing within 10 months post-diagnosis. CONCLUSIONS: Ocular metastasis in breast cancer is rare (0.5%) but signifies poor outcome. It is linked to ILC and concurrent brain metastasis. Primary treatment involves radiation therapy, with a favorable visual prognosis.

Intense prostate-specific membrane antigen receptor expression in coronary artery pypass graft scar tissue: A potential molecular imaging pitfall.

68Gallium-PSMA positron emission tomography/computer tomography has been utilized recently for the diagnosis and staging of prostate cancer. PSMA is a transmembrane protein that is expressed not only in the prostate gland but also in other tissues. While some pitfalls have been addressed, there are still uncertainties. Herein, we report a 79-year-old male with prostate cancer who underwent a PSMA scan after coronary artery bypass graft surgery, revealing disease progression and PSMA-avid foci at the surgical stitch sites. This report discusses the immunohistochemical and molecular imaging mechanisms underlying PSMA expression in surgical scar tissues, providing critical insights for optimizing radiologic reporting in such situations.

Six country vignettes: Strengthening radiotherapy and theranostics.

BACKGROUND: For cancer patient populations worldwide, the synchronous scale-up of diagnostics and treatments yields meaningful gains in survival and quality of life. Among advanced cancer therapies, radiotherapy (RT) and theranostics are key to achieving practical, high-quality, and personalized precision medicine - targeting disease manifestations of individual patients and broad populations, alike. Aiming to learn from one another across different world regions, the six country vignettes presented here depict both challenges and victories in de novo establishment or improvement of RT and theranostics infrastructure. METHODS: The International Atomic Energy Agency (IAEA) convened global RT and theranostics experts from diverse world regions and contexts to identify relevant challenges and report progress in their own six countries: Belgium, Brazil, Costa Rica, Jordan, Mongolia, and South Africa. These accounts are collated, compared, and contrasted herein. RESULTS: Common challenges persist which could be more strategically assessed and addressed. A quantifiable discrepancy entails personnel. The estimated radiation oncologists (ROs), nuclear medicine physicians (NMPs), and medical physicists (MPs for RT and nuclear medicine) per million inhabitants in the six collective countries respectively range between 2.69-38.00 ROs, 1.00-26.00 NMPs, and 0.30-3.45 MPs (Table 1), reflecting country-to-country inequities which largely match World Bank country-income stratifications. CONCLUSION: Established goals for RT and nuclear medicine advancement worldwide have proven elusive. The pace of progress could be hastened by enhanced approaches such as more sustainably phased implementation; better multinational networking to share lessons learned; routine quality and safety audits; as well as capacity building employing innovative, resource-sparing, cutting-edge technologic approaches. Bodies such as ministries of health, professional societies, and the IAEA shall serve critical roles in convening and coordinating more innovative RT and theranostics translational research, including expanding nuanced global database metrics to inform, reach, and potentiate milestones most meaningfully. POLICY SUMMARY: Aligned with WHO 25×25 NCDs target; WHA70.12 and WHA76.5 resolutions.