Guiding principles on the education and practice of theranostics.

PURPOSE: The recent development and approval of new diagnostic imaging and therapy approaches in the field of theranostics have revolutionised nuclear medicine practice. To ensure the provision of these new imaging and therapy approaches in a safe and high-quality manner, training of nuclear medicine physicians and qualified specialists is paramount. This is required for trainees who are learning theranostics practice, and for ensuring minimum standards for knowledge and competency in existing practising specialists. METHODS: To address the need for a training curriculum in theranostics that would be utilised at a global level, a Consultancy Meeting was held at the IAEA in May 2023, with participation by experts in radiopharmaceutical therapy and theranostics including representatives of major international organisations relevant to theranostics practice. RESULTS: Through extensive discussions and review of existing curriculum and guidelines, a harmonised training program for theranostics was developed, which aims to ensure safe and high quality theranostics practice in all countries. CONCLUSION: The guiding principles for theranostics training outlined in this paper have immediate relevance for the safe and effective practice of theranostics.

Modifiable risk factors for cancer in the middle East and North Africa: a scoping review.

PURPOSE: This scoping review examines controllable predisposing factors attributable to cancer in the Middle East and North Africa (MENA) region's adult population, highlighting opportunities to enhance cancer prevention programs. DESIGN: We systematically searched the PubMed, Science Direct, and CINAHL, EMBASE, and Cochrane Library databases from 1997 to 2022 for articles reporting on the impact of modifiable risk factors on adult patients with cancer in the MENA region. RESULTS: The review identified 42 relevant articles, revealing that tobacco consumption, obesity, physical inactivity, and diet are significant modifiable risk factors for cancer in the region. Tobacco smoking is a leading cause of lung, bladder, squamous cell carcinoma, and colorectal cancer. A shift towards a westernized, calorie-dense diet has been observed, with some evidence suggesting that a Mediterranean diet may be protective against cancer. Obesity is a known risk factor for cancer, particularly breast malignancy, but further research is needed to determine its impact in the MENA region. Physical inactivity has been linked to colorectal cancer, but more studies are required to establish this relationship conclusively. Alcohol consumption, infections, and exposure to environmental carcinogens are additional risk factors, although the literature on these topics is limited. CONCLUSION: The review emphasizes the need for further research and the development of targeted cancer prevention strategies in the MENA region.

National and local diagnostic reference levels for adult18F-FDG and CT in Jordanian PET/CT: findings and implications in practice.

This study aims to report the findings of Jordanian national diagnostic reference level (NDRL) survey for fluorodeoxyglucose (18F-FDG) and local diagnostic reference level (LDRL) of computed tomography (CT) used for attenuation correction and anatomical localisation (AC-AL); and AC and diagnostic CT (AC-DX) within the context of whole-body WB and half-body HB adult oncology PET/CT scanning. Two-structured questionnaires were prepared to gather the necessary information: dosimetry data, patient demographics, equipment specification, and acquisition protocols for identified18F-FDG PET/CT procedures. The NDRL and achievable dose were reported based on the 75th and 50th percentiles for18F-FDG administered activity (AA), respectively. The LDRL was reported based on the 50th percentile for (CTDIvol) and (DLP). Data from 562 patients from four Jordanian PET/CT centres were collected. The survey revealed that Jordanian NDRL for AA (303 MBq) was within the acceptable range compared to the published-peer NDRL data (240-590 MBq). However, the18F-FDG AA varied across the participated PET/CT centres. The reported LDRL CTDIvoland DLP of CT used for (AC-AL) was 4.3 mGy and 459.3 mGy.cm for HB CT scan range, and 4.1 mGy and 659.9 mGy.cm for WB CT scans. The reported LDRL for CTDIvoland DLP for HB CT was higher when compared with the United Kingdom (3.2 mGy and 310 mGy.cm). Concurrently, in the context of WB CT, the reported values (i.e. CTDIvol and DLP) were also higher than both Kuwait (3.6 mGy and 659 mGy.cm) and Slovenia (3.6 mGy and 676 mGy.cm). The reported HB CT(AC-DX) was higher than Nordic, New Zealand and Swiss NDRLs and for WB (AC-DX) CT it was higher than Swiss NDRLs. This study reported the first Jordanian NDRL for18F-FDG and LDRL for HB and WB CT associated with18F-FDG PET/CT scans. This data is useful for Jordanian PET/CT centres to compare their LDRL to the suggested DRLs and utilise it in the process of optimising CT radiation doses.

Initial clinical experience using 68Ga-FAPI-46 PET/CT for detecting various cancer types.

OBJECTIVE: Numerous studies have shown that gallium-68-labeled fibroblast activation protein inhibitor (68Ga-FAPI) positron emission tomography/computed tomography (PET/CT) scans would yield high intra-tumoral tracer uptake and low uptake in normal tissues as background, thus allowing for excellent visualization of lesions in the cancer microenvironment. This study set out to compare the suitability of novel 68Ga-FAPI-46 PET versus routine fluorine-18-fluorodeoxyglucose (18F-FDG) PET and other few cases of 68Ga-DOTATATE/68Ga-Pentixafor PET/CT for the assessment of different types of cancer. SUBJECTS AND METHODS: A retrospective analysis of 11 patients (6 males, 5 females; average age: 53 years, range: 10-58 years) with histopathologically confirmed, well-differentiated adenocarcinoma, medullar thyroid cancer (MTC), papillary thyroid carcinoma (PTC), cervical, gastric, glioblastoma multiform (GBM), colon, Ewing's sarcoma, and breast cancer was performed. These patients underwent PET/CT scans using four different radiotracers (9 18F-FDG, 11 68Ga- FAPI, 3 68Ga-DOTATATE, and 1 68Ga-Pentixafor). The patients' PET/CT images were visually evaluated for cancer detection, and analyzed semi-quantitatively through image- derived metrics, such as target-to-background ratio (TBR) and maximum standardized uptake value (SUVmax), for recurrence and metastasis. RESULTS: The study of 11 patients revealed that 68Ga-FAPI-46 was more effective than other tracers for detecting metastases, with 55 vs. 49 metastases in the lymph nodes, 4 vs. 3 in the liver, and 4 vs. 3 in the bones detected in comparison to 18F-FDG. No significant differences were observed in 68Ga-DOTATATE and 68Ga-Pentixafor PET images. In addition, in five patients, the SUVmax and TBR values in 68Ga-FAPI-46 PET images were significantly higher than those in 18F-FDG PET images for lymph nodes and bone metastases. Although the SUVmax in 68Ga-FAPI-46 and 18F-FDG PET images for liver metastases was comparable, 68Ga-FAPI- 46 had a significantly higher TBR than 18F-FDG. CONCLUSION: Our findings suggest that FAPI PET/CT is not suitable for evaluating GBM and Ewing sarcoma but generally outperforms 18F-FDG PET/CT in various types of breast cancer, gastrointestinal, gynecological, PTC and MTC. However, larger trials are needed to validate these preliminary findings.

Impact of 18F-FDG PET/CT, CT and EBUS/TBNA on preoperative mediastinal nodal staging of NSCLC.

BACKGROUND: Staging of non-small-cell lung cancer (NSCLC) is a multidisciplinary process involving imaging, endoscopic and surgical techniques. This study aims at investigating the diagnostic accuracy of 18F-FDG PET/CT, CT scan, and endobronchial ultrasound/transbronchial needle aspirate (EBUS/TBNA) in preoperative mediastinal lymph nodes (MLNs) staging of NSCLC. METHODS: We identified all patients who were diagnosed with NSCLC at the King Hussein Cancer Center in Amman, Jordan, between July 2011 and December 2017. We collected their relevant clinical, radiological, and histopathological findings. The per-patient analysis was performed on all patients (N = 101) and then on those with histopathological confirmation (N = 57), followed by a per-lymph-node-station basis overall, and then according to distinct N-stage categories. RESULTS: 18F-FDG PET/CT, in comparison to CT, had a better sensitivity (90.5% vs. 75%, p = 0.04) overall and in patients with histopathological confirmation (83.3% vs. 54.6%), and better specificity (60.5% vs. 43.6%, p = 0.01) overall and in patients with histopathological confirmation in MLN staging (60.6% vs. 38.2%). Negative predictive value of mediastinoscopy, EBUS/TBNA, and 18F-FDG PET/CT were (87.1%), (90.91%), and (83.33%) respectively. The overall accuracy was highest for mediastinoscopy (88.6%) and EBUS/TBNA (88.2%), followed by 18F-FDG PET/CT (70.2%). Dividing patients into N1 disease vs. those with N2/N3 disease yielded similar findings. Comparison between 18F-FDG PET/CT and EBUS/TBNA in patients with histopathological confirmation shows 28 correlated true positive and true negative findings with final N-staging. In four patients, 18F-FDG PET/CT detected metastatic MLNs that would have otherwise remained undiscovered by EBUS/TBNA alone. Lymph nodes with a maximal standardized uptake value (SUVmax) more than 3 were significantly more likely to be true-positive. CONCLUSION: Multimodality staging of the MLNs in NSCLC is essential to provide accurate staging and the appropriate treatment. 18F-FDG PET/CT has better overall diagnostic utility when compared to the CT scan. The NPV of 18F-FDG PET/CT in MLNs is reliable and comparable to the NPV of EBUS/TBNA. SUVmax of MLNs can help in predicting metastases, but nevertheless, a positive 18F-FDG PET/CT MLNs particularly if such a result would change the treatment plan, should be verified histopathologically.

Assessment of segmental left ventricular thickening in diabetic type II obese patients with normal myocardial perfusion scan.

OBJECTIVE: The aim of this study is to investigate whether gated single photo emission tomography (gSPET) can be used to detect subclinical left ventricular systolic dysfunction (LVSD) in obese diabetic type II patients. SUBJECTS AND METHODS: We retrospectively reviewed gSPET images of 190 patients with diabetes mellitus type II (DM II) (137 females and 53 males) with normal myocardial perfusion and normal ejection fraction (EF). Standardized twenty segment polar maps of thickening and motion were generated. Correlation between body mass index (BMI) and thickening for each segment was performed. RESULTS: Statistically significant results were reported in female patients including: negative correlation between BMI and EF (-0.19, P=0.03). End diastolic volume (EDV) also significantly increased with increasing BMI (0.25, P<0.01). There was also statistically significant negative correlation between septal thickening and BMI segment 15 (-0.19, P=0.02), segment 16 (-0.22, P=0.01), segment 18 (-0.20, P=0.01), segment 19 (-0.25, P=0.003), segment 20 (-0.2, P=0.02)]. No statistical significant correlation was found between thickening and BMI in male patients. CONCLUSION: This is the first time where thickening as measured by gSPET has been used to demonstrate subclinical LVSD in DM II obese patients. The relationship between gender and obesity on cardiovascular function and structure needs further investigations.

Unusual presentation of non-small cell lung cancer with clival metastases: Case report.

A 37-year-old female with unusual presentation of metastatic non-small cell lung cancer (NSCLC), as she presented with symptoms related to clival bone metastases. This case highlights the unpredictable presentations and the variety of metastatic sites of which metastatic NSCLC could be presented.

Primary Central Nervous System Lymphoma Presenting as a Solitary Fourth Ventricular Mass: A Case Report.

The occurrence of primary fourth ventricular lymphoma is an exceptionally uncommon phenomenon. Here, we present a case of lymphoma in the fourth ventricle in a 30-year-old male who presented with progressive headache and vertigo over the last one month of his presentation. Preoperative MRI revealed a space-occupying lesion of the fourth ventricle. Pathological analysis following complete resection confirmed the lesion as primary central nervous system lymphoma. The patient underwent chemotherapy following the MTR (methotrexate, temozolomide, and rituximab) protocol with four months of uneventful follow-up, indicating no disease recurrence. Therefore, clinicians are advised to consider the potential presence of lymphoma as part of the differential diagnosis for space-occupying lesions, especially when there is a combination of clinical deterioration and rapid imaging progression.

Radiotheranostics Global Market and Future Developments.

Radiotheranostics, a combination of diagnostic and therapeutic approaches, was first utilized in cancer management using radiopharmaceuticals to both image and selectively treat specific cancer subtypes nearly a century ago. Radiotheranostic strategies rooted in nuclear medicine have revolutionized the treatment landscape for individuals diagnosed with prostate cancer and neuroendocrine tumors in the past 10 years. In specific contexts, these approaches have emerged as the prevailing standard, yielding numerous positive results. The field of radiotheranostics shows great potential for future clinical applications. This article aims to examine the key factors that will contribute to the success of radiotheranostics in the future, as well as the current challenges and potential strategies to overcome them, with insight into the global radiotheranostic market.

Unmasking Coincident Hodgkin Lymphoma and Giant Cell Tumor: Insights from [18F] FDG PET/CT.

Tenosynovial giant cell tumors represent a group of typically non-malignant tumors found within the joints and soft tissues. The occurrence of tenosynovial giant cell tumor alongside hematologic malignancies is an infrequent finding. Herein, we report a patient who presented with coinciding Hodgkin Lymphoma (HL) and tenosynovial giant cell tumor before chemotherapy initiation. The case was discovered during initial assessment using [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) imaging for HL staging. An unrelated hypermetabolic mass within the left knee joint led to the discovery of this unusual case, which led to a CT-guided biopsy and tenosynovial giant cell tumor discovery. This was clearly demonstrated in interim and end-of-therapy PET/CT studies when all lymphomatous lesions had resolved but the tenosynovial giant cell tumor remained. This case serves as a reminder of the intricate nature of oncological pathology and emphasizes the need for thorough and vigilant diagnostic evaluation for optimal management plan.

Cerebral and Muscular Metastases From Prostate Adenocarcinoma Initially Depicted by 177 Lu-PSMA SPECT/CT.

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.

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.

A rare presentation of thyroid malignant peripheral nerve sheath tumor in neurofibromatosis type 1 delineated by FDG PET/CT: A case report and literature review.

Malignant peripheral nerve sheath tumors (MPNST) are rare, aggressive soft tissue sarcomas that arise from peripheral nerves and often present a diagnostic and therapeutic challenge. They can occur sporadically or in association with neurofibromatosis type 1 (NF1), a genetic disorder caused by mutations in the NF1 gene. This report presents the unique case of a 33-year-old male with progressive dry cough, hoarseness, and neck swelling who underwent a total thyroidectomy, revealing a high-grade malignant peripheral nerve sheath tumor invading the thyroid. FDG PET/CT led to the additional diagnosis of NF1. This case stands out due to the rarity of finding an MPNST within the thyroid and the simultaneous identification of NF1. It underscores the importance of screening MPNST patients for NF1 and vice versa, spotlighting the expanding role of FDG PET/CT in comprehensive evaluations. To our knowledge, this report presents the first case of NF1-associated MPNST with thyroid involvement worldwide.

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.

Comprehensive Analysis of Metastatic Prostate Cancer: Real-World Data From the Middle East.

PURPOSE: Metastatic prostate cancer (Pca) is a complex disease with diverse clinical characteristics and outcomes across the geographical distribution. Herein, we present a series of patients from the Middle East, aiming at identifying disease outcomes and prognostic factors specific to this regional context. METHODS AND MATERIALS: This is a retrospective study of patients with metastatic Pca, diagnosed at King Hussein Cancer Center, Jordan, between 2006 and 2018. Survival was estimated using the Kaplan-Meier method and compared using the log-rank test. Factors that significantly affected overall survival (OS) in the univariable analysis were examined in a multivariable Cox regression analysis. RESULTS: A total of 188 patients with metastatic Pca were included in this analysis, of whom 168 (89%) had de novo metastatic disease. The median age at diagnosis was 68 years, 144 (77%) had bone metastasis, 32 (17%) had visceral metastasis, and 126 (67%) had high-volume disease. At a median follow-up of 67 months, the median OS was 44.3 months. The following factors predicted inferior OS in univariable analysis: smoking, normal BMI, high-volume disease, high alkaline phosphatase (ALP), previous local therapy for prostate, and orchiectomy versus medical androgen deprivation therapy (ADT). On multivariable analysis, high-volume disease (hazard ratio [HR], 1.92 [95% CI, 1.17 to 3.13]; P = .0094), high ALP (HR, 2.136 [95% CI, 1.38 to 3.31]; P < .001), and orchiectomy (HR, 2.40 [95% CI, 1.51 to 3.82]; P < .001) emerged as independent factors for inferior OS. CONCLUSION: Metastatic Pca outcomes in our population closely align with the global benchmark. High volume status, elevated ALP, and performance of surgical as opposed to medical ADT emerge as prognostic indicators of poor survival.

18 F-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, 18 F-FDG PET/CT revealed medullary and extramedullary hepatosplenic and thyroid cartilage involvement, concluding an overall picture of an atypical and extensive extramedullary myelomatous disease.

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.

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.