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.

Assessing nuclear medicine practices: a critical evaluation of QUANUM through a quality improvement perspective and its wider relevance.

Quality Management Audits in Nuclear Medicine (QUANUM) is an initiative conceived by the International Atomic Energy Agency to enhance global standards in Nuclear Medicine practices. Acknowledging the intricate regulatory frameworks and the necessity for multidisciplinary collaboration, QUANUM has gained global acceptance, demonstrating widespread implementation and positive impacts on patient care. This manuscript critically evaluates the QUANUM program through the lens of quality improvement (QI), by employing established and validated QI tools. Our analysis identifies areas of conformance, underscores key strengths inherent to QUANUM, and pinpoints further learning opportunities for continuous enhancement. Additionally, we assert that the insights derived from scrutinizing this global project within Nuclear Medicine, have valuable implications for departments aspiring for establishing good quality management systems, thereby contributing to the improvement of patient care.

Utility of a simplified [18F] sodium fluoride PET imaging method to quantify bone metabolic flux for a wide range of clinical applications.

We review the rationale, methodology, and clinical utility of quantitative [18F] sodium fluoride ([18F]NaF) positron emission tomography-computed tomography (PET-CT) imaging to measure bone metabolic flux (Ki, also known as bone plasma clearance), a measurement indicative of the local rate of bone formation at the chosen region of interest. We review the bone remodelling cycle and explain what aspects of bone remodelling are addressed by [18F]NaF PET-CT. We explain how the technique works, what measurements are involved, and what makes [18F]NaF PET-CT a useful tool for the study of bone remodelling. We discuss how these measurements can be simplified without loss of accuracy to make the technique more accessible. Finally, we briefly review some key clinical applications and discuss the potential for future developments. We hope that the simplified method described here will assist in promoting the wider use of the technique.

Cardiac sarcoidosis: the role of cardiac MRI and 18F-FDG-PET/CT in the diagnosis and treatment follow-up.

Sarcoidosis is a multi-factorial inflammatory disease characterised by the formation of non-caseating granulomas in the affected organs. Cardiac involvement can be the first, and occasionally the only, manifestation of sarcoidosis. The prevalence of cardiac sarcoidosis (CS) is higher than previously suspected. CS is associated with increased morbidity and mortality. Thus, early diagnosis is critical to introducing immunosuppressive therapy that could prevent an adverse outcome. Endomyocardial biopsy (EMB) has limited utility in the diagnostic pathway of patients with suspected CS. As a result, advanced imaging modalities, i.e. cardiac magnetic resonance imaging (MRI) and positron emission tomography with 18F-Fluorodeoxyglucose/computed tomography scan (18F-FDG-PET/CT), have emerged as alternative tools for diagnosing CS and might be considered the new 'gold standard'. This focused review will discuss the epidemiology and pathology of CS, when to suspect and evaluate CS, highlight the complementary roles of cardiac MRI and 18F-FDG-PET/CT, and their diagnostic and prognostic values in CS, in the current content of guidelines for the diagnostic workflow of CS.

Revising and exploring the variations in methodologies for establishing the diagnostic reference levels for paediatric PET/CT imaging.

PET-computed tomography (PET/CT) is a hybrid imaging technique that combines anatomical and functional information; to investigate primary cancers, stage tumours, and track treatment response in paediatric oncology patients. However, there is debate in the literature about whether PET/CT could increase the risk of cancer in children, as the machine is utilizing two types of radiation, and paediatric patients have faster cell division and longer life expectancy. Therefore, it is essential to minimize radiation exposure by justifying and optimizing PET/CT examinations and ensure an acceptable image quality. Establishing diagnostic reference levels (DRLs) is a crucial quantitative indicator and effective tool to optimize paediatric imaging procedures. This review aimed to distinguish and acknowledge variations among published DRLs for paediatric patients in PET/CT procedures. A search of relevant articles was conducted using databases, that is, Embase, Scopus, Web of Science, and Medline, using the keywords: PET-computed tomography, computed tomography, PET, radiopharmaceutical, DRL, and their synonyms. Only English and full-text articles were included, with no limitations on the publication year. After the screening, four articles were selected, and the review reveals different DRL approaches for paediatric patients undergoing PET/CT, with primary variations observed in patient selection criteria, reporting of radiation dose values, and PET/CT equipment. The study suggests that future DRL methods for paediatric patients should prioritize data collection in accordance with international guidelines to better understand PET/CT dose discrepancies while also striving to optimize radiation doses without compromising the quality of PET/CT images.

Lessons from a 3-Year Review of PSMA PET-CT in a Tertiary Setting: Can We Fine Tune Referral Criteria by Identifying Factors Predicting Positivity and Negativity?

AIM OF THE STUDY: To draw inferences from a retrospective evaluation of PSMA PET CT scans performed for the evaluation of biochemical recurrence. MATERIAL AND METHODS: A retrospective analysis of 295 PSMA PET CT scans spanning 3 years between 2020 and 2022 was undertaken. RESULTS: Of 295 PET CT scans, 179 were positive, 66 were negative and 50 had indeterminate findings. In the positive group, 67 had radical prostatectomy and PSMA avid lesions were seen most commonly in pelvic lymph nodes. The remaining 112 positive scans were in the non-radical prostatectomy group; 25 had recurrence only in the prostate, 17 had recurrence involving the prostate bed; 28 had no recurrence in the prostate gland, while 42 had recurrence in the prostate as well as in extra-prostatic sites. Overall, in the non-prostatectomy group, 75% of the population was harboring a PSMA avid lesion in the prostate gland while in the remaining 25% of the population, recurrence did not involve the prostate gland. The majority of indeterminate findings were seen in small pelvic or retroperitoneal lymph nodes or skeletal regions (ribs/others) and in nine patients indeterminate focus was seen in the prostate bed only. Follow-up PSMA PET CT was helpful in prior indeterminate findings and unexplained PSA rise. CONCLUSION: A higher recurrence in the prostate bed while evaluating biochemical recurrence prompts the following: question: should prostatectomy be offered more proactively? Follow-up PSMA PET CT is helpful for indeterminate findings; a PSA rise of 0.7 ng/mL in 6 months can result in positive PSMA PET CT while negative scans can be seen up to a 2 ng/mL PSA rise in 6 months.

A Review on the Usage of Bone Single-Photon Emission Computed Tomography/Computed Tomography in Detecting Skeletal Metastases in the Post-COVID-19 Era: Is it Time to Ditch Planar and Single-Photon Emission Computed Tomography only Gamma Camera Systems?

Planar whole-body bone scanning (WBS) is widely used to evaluate skeletal lesions seen in cancer and noncancer cases. Frequently, degenerative, or other benign bony changes may give rise to indeterminate lesions that mimic bone metastases. In the post-COVID-19 era, there is an evolutionary phase that puts importance on global development and adaptability, which encompasses to include nuclear medicine practices worldwide. Single-photon emission computed tomography/computed tomography (SPECT/CT) can be used to improve the characterization of these lesions and help to resolve the diagnostic conundrum while reducing the need for patients to undergo multiple different examinations at various imaging departments. The fusion of SPECT and CT allows morphological characterization of functional abnormality detected by focal tracer uptake on planar scintigraphy, which provides a one-stop center imaging in nuclear medicine departments. The objective of this study was to review the diagnostic accuracy of SPECT/CT in diagnosing bone metastases in a variety of oncology and nononcology cases and to determine the feasibility of performing bone SPECT/CT in all suspected cancer cases, including cases of bone infection instead of planar imaging alone. The utilization of hybrid SPECT/CT in indeterminate bone lesions detected on planar WBS can significantly increase the diagnostic confidence and accuracy of image interpretation. Recognition of patterns of disease identified using hybrid imaging can improve the management of patients with potentially lower costs in the long term. Currently, hybrid SPECT/CT machines are becoming a norm in nuclear medicine departments, thus potentially making single planar application machines obsolete in the near future. We hypothesize that in the interest of providing a meaningful interpretation of isotope bone scans, the default protocol should involve the option of acquiring SPECT/CT images rather than relying on whole-body scans only. Departments choosing to upgrade existing equipment or those choosing to invest in only one gamma camera should proactively opt for hybrid SPECT/CT systems.

FAPI PET/CT Imaging-An Updated Review.

Despite revolutionizing the field of oncological imaging, Positron Emission Tomography (PET) with [18F]Fluorodeoxyglucose (FDG) as its workhorse is limited by a lack of specificity and low sensitivity in certain tumor subtypes. Fibroblast activation protein (FAP), a type II transmembrane glycoprotein, is expressed by cancer-associated fibroblasts (CAFs) that form a major component of the tumor stroma. FAP holds the promise to be a pan-cancer target, owing to its selective over-expression in a vast majority of neoplasms, particularly epithelial cancers. Several radiolabeled FAP inhibitors (FAPI) have been developed for molecular imaging and potential theranostic applications. Preliminary data on FAPI PET/CT remains encouraging, with extensive multi-disciplinary clinical research currently underway. This review summarizes the existing literature on FAPI PET/CT imaging with an emphasis on diagnostic applications, comparison with FDG, pitfalls, and future directions.

The Clinical Significance of Incidental GIT Uptake on PET/CT: Radiologic, Endoscopic, and Pathologic Correlation.

Incidental gastrointestinal tract (GIT) [18F]-Fluorodeoxyglucose (FDG) uptake in positron emission technology/computed tomography (PET/CT) is an unexpected and often complicated finding for clinicians. This retrospective study reviewed 8991 charts of patients who underwent PET/CT: 440 patients had incidental GIT uptake, of which 80 underwent endoscopy. Patient characteristics, imaging parameters, and endoscopic findings were studied. Of the 80 patients, 31 had cancer/pre-cancer lesions (16 carcinomas; 15 pre-malignant polyps). Compared to patients with benign/absent lesions, patients with cancer/pre-cancer lesions were significantly older (p = 0.01), underwent PET/CT for primary evaluation/staging of cancer (p = 0.03), had focal GIT uptake (p = 0.04), and had lower GIT uptake (p = 0.004). Among patients with focal uptake, an SUVmax of 9.2 had the highest sensitivity (0.76) and specificity (0.885) in detecting cancer/pre-cancerous lesions. Lower GIT uptake was most common in the sigmoid colon, and upper GIT uptake was most frequent in the stomach. In a bivariate analysis, predictors of cancer/pre-cancer were older age, PET/CT indicated for primary evaluation, focal uptake, uptake in the lower GIT, and higher SUVmax. Further endoscopic investigation is warranted for patients with incidental GIT uptake, especially in the elderly or those presenting for primary evaluation with PET/CT, with the following findings on imaging: lower GIT uptake, focal uptake, or high SUVmax.

Crossed Cerebellar Diaschisis in Thalamic Lymphoma on 18 F-FDG PET/CT.

Primary central nervous system lymphomas (PCNSLs) are extranodal variant forms of non-Hodgkin lymphoma arising within the brain parenchyma, leptomeninges, or spinal cord. PCNSL can present with varied neurological symptoms and imaging findings, making diagnosis without biopsy difficult. PCNSLs are highly aggressive, causing rapid deterioration, but are responsive to chemotherapy and radiotherapy making early diagnosis important. Crossed cerebellar diaschisis (CCD) is mostly seen with cerebral cortex vascular insults and is rarely reported with thalamic lesions and even rarer with thalamic lymphoma. However, CCD has also been described in other brain tumors (including primary glioma), chronic subdural hematoma, congenital insults, intracranial infections, and various dementia subtypes. We present a rare case of thalamic lymphoma evaluated with positron emission tomography/computed tomography that showed hypermetabolism of thalamus and associated hypometabolism in ipsilateral cerebral cortex and contralateral cerebellum representing CCD.

123-Iodine MIBG in the Assessment of Sympathetic Denervation in Ogilvie's Syndrome.

123-Iodine metaiodobenzylguanidine (I-123 MIBG) imaging is frequently used in the assessment of sympathetic innervation and autonomic dysfunction in patients with cardiac failure, neurodegenerative Parkinson's syndrome, multiple system atrophy, myotonic dystrophy, and diabetic mellitus. The etiology of pseudo-obstruction remains unknown with likely imbalance between sympathetic and parasympathetic innervation proposed as a hypothesis. We present a case demonstrating the utility of I-123 MIBG scintigraphy for evaluating a case of pseudo-obstruction requiring frequent hospitalization due to progressive complex autoimmune neurological disorder.

Investigation and assessment of adrenal incidentalomas.

With the increasing volume of diagnostic imaging undertaken in an ageing population, adrenal incidentalomas (AIs) are increasingly commonly seen. These masses are most likely to be benign, but a small proportion may be malignant. Similarly, they are usually non-functional, but ∼14% are functional, ie hormone-secreting tumours. Clinical, biochemical and radiological assessment is mandated to stratify patients into those requiring radiological surveillance, medical management or surgical intervention or who can be discharged. Mass characteristics on cross-sectional (CT/MRI) imaging influence the need for radiological surveillance. Functional tumours where excess cortisol, aldosterone or catecholamine are secreted should be excluded, with mild autonomous cortisol secretion (MACS) and primary aldosteronism (PA) as the two most common functional states. MACS and PA are associated with an increased risk of cardiometabolic disease (eg hypertension, type 2 diabetes) and cardiovascular morbidity/mortality (eg coronary heart disease). Multidisciplinary management is critical for selected cases; the majority of adrenal incidentalomas only require a single assessment.

Prone versus Supine FDG PET/CT in the Staging of Breast Cancer.

Supine [18F]Fluorodeoxyglucose (FDG) positron emission technology/computed tomography (PET/CT) is a commonly used modality for the initial staging of breast cancer, and several previous studies have shown superior sensitivity and specificity of prone FDG PET/CT in comparison to its supine counterpart. This retrospective study included 25 females with breast cancer referred for staging. They underwent supine FDG PET/CT followed by prone FDG PET/CT. The outcomes were: number of primary breast lesions, anatomical site of FDG-avid lymph nodes (LNs), and number and type of bone lesions, with SUVmax of all corresponding parameters. Performance was superior in prone acquisition compared to supine acquisition, with the respective results: 29 vs. 22 breast tumor lesions detected, 62 vs. 27 FDG-avid axillary LNs detected, sensitivity of 68% vs. 57%, specificity of 64% vs. 53%. The detection rate of axillary LNs in the prone position was significantly higher (p = 0.001). SUVmax for breast tumor lesions (p = 0.000) and number of detected axillary LNs (p = 0.002) were significantly higher in prone acquisition. Five patients were upstaged after experts read the prone acquisition. Prone FDG PET/CT acquisition is a promising technique in detecting primary breast lesions and metastatic LNs possibly missed in supine acquisition, which may lead to change in patient staging and management.

Review of the role of MRI and 18 F-sodium fluoride PET/computed tomography in the characterisation of spinal bone metastases in a cohort of patients with breast cancer.

PURPOSE: The purpose of the study was to compare the diagnostic accuracy and relative usefulness of MRI and 18 F-NaF (sodium fluoride) PET/computed tomography (CT) for detection of spinal bone metastases in a cohort of patients with high-risk breast cancer (BrCa). METHODS: A retrospective study was conducted of patient and lesion-based analyses on 66 consecutive patients (median age, 62.5 years; age range, 33-91 years) who underwent Spinal MRI as well as 18 F-NaF PET-CT for restaging of newly diagnosed recurrent BrCa with no previous bone metastases. Both scans were performed within 20 days of each other. Review of prior images, clinical decisions, multi-disciplinary team discussions and decisions as well as follow-up information including scans and definitive tests was performed at least 12 months after the initial scans. RESULTS: Of the 66 patients reviewed, 26 patients had documented spinal bone metastases on one or both modalities, while 40 patients were considered bone disease free on both modalities and this was confirmed on follow-up. On lesion-based analysis, the findings of 18 F-NaF PET-CT and spinal MRI were concordant in 51 patients (77.3%). In the remaining patients, 18 F-NaF PET/CT detected more lesions in 4 patients (7.6%) and MRI detected more lesions in 10 patients (15.1%). Interestingly, there was a very high, 97 % concordance (64 patients) between spinal MRI and 18 F-NaF PET-CT when staging of spinal bone metastasis was taken into consideration. In one patient MRI identified two spinal bone metastases which were not seen on 18 F-NaF PET/CT; and, in one patient 18 F-NaF PET/CT showed few spinal bone metastases when no lesion was seen on MRI. CONCLUSIONS: Our study showed a high level of concordance between 18 F NaF PET-CT and spinal MRI within the setting of detection of bone lesions in the spine in a cohort of patients with high-risk BrCa. In our opinion, this high level of concordance negates the need to perform both tests although each test may be indicated for slightly different reasons. Further longitudinal studies across a longer duration and more centres may provide more definitive answers.

Factors Influencing Outcome Post-Radium-223 Dichloride in Castrate Resistant Prostate Cancer: A Review of Some Real-World Challenges.

Aim Radium-223 has been the first-approved targeted Alpha therapy agent. We retrospectively assessed different factors influencing the overall survival (OS) and patient management. Setting and Design Thirty-two metastatic castration-resistant prostate cancer (mCRPC) patients' hematological parameters, number of cycles, performance status, and toxicities were evaluated for OS. Radium 223 dichloride (Radium-223) was administered every 4 weeks for a maximum of six cycles. Primary and secondary end points were OS, progression free survival (PFS), therapy toxicities, change in performance status, biochemical response, and skeletal-related events (SREs). Materials and Methods Patients' median age was 77 years (range: 57-90 years) and median follow-up was 399 days (range: 5-1,761 days). A total of 163 cycles were administered in 32 patients, with 4 or less cycles in 8 patients (25%) and 5 or more cycles in 24 patients (75%). Among eight patients with 4 or less cycles, three patients died, of which two patients died due to neutropenic sepsis. Statistical Analysis Mann-Whitney test was used to compare the cycle groups; Spearman's correlation coefficient was used to see the relation of different variables with OS. Log rank test was used for group comparison while Kaplan-Meier survivorship was used for OS. Results Statistical correlation was seen between the number of cycles ( p =0.037) and hemoglobin ( p =0.028). Kaplan-Meier OS ( p =0.038) was correlated with the number of cycles (≤ 4 cycles and ≥ 5 cycles). OS was 173 days in patients with one to four cycles, 226 days in five cycles, and 493 days in six cycles. Myelosuppression leading to stopping of full six cycles was seen in 7 of 32 patients (22%) and significantly correlated to inferior OS ( p =0.048). Conclusion Higher number of Radium-223 cycles was seen to be associated with better OS. Prior myelosuppression was associated with poor OS. Patients with better hematological profile were more likely to complete the maximum number of the cycles with a better OS.

Indeterminate skeletal and lymph node lesion on 18F PSMA 1007 PET/CT scanning: lessons from a review at 12 months with PSMA-RADS.

AIMS OF THE STUDY: The study utilizes the prostate-specific membrane antigen-reporting and data system (PSMA-RADS) version 1.0 in a real-world patient scenario in the evaluation of equivocal lesions using the PSMA-RADS categorization for patient management and communication in multidisciplinary team (MDT) meetings. METHODS: A retrospective analysis of 203 patients who had 18F PSMA PET/CT for either restaging or staging over 12 months was undertaken. The scans were evaluated for local disease, lymph node involvement and distant metastases. The scan findings were classified as suspicious for metastases, and equivocal and benign lesions. Experience with PSMA ligand imaging was considered while classifying the lesions, equivocal lesions were assessed with PSMA-RADS and followed up with complementary imaging and/or clinical follow-up assessment or MDT for further patient management. RESULTS: A total of 91 of 203 patients had equivocal lesions. Follow-up assessment was performed in 47 of 91 patients with imaging ( n = 36) or MDT discussion ( n = 11).On follow-up imaging ( n = 36), equivocal lesion was seen in skeletal lesions ( n = 24), pelvic lymph nodes ( n = 6), both skeletal and pelvic nodes ( n = 4), hilar and mediastinal lymph nodes ( n = 1) and spleen ( n = 1). The patients were reclassified as benign, metastatic with few lesion remained equivocal. Overall follow-up assessment impacted clinical management in 47% patients. CONCLUSION: 18F PSMA PET/CT may show equivocal lesions; many of them in the skeleton, a small proportion of which are ultimately proven metastatic. In contrast, a higher proportion of the equivocal nodes in the pelvis end up being metastatic on follow-up. A structured reporting with PSMA-RADS grading helps in the proper classification of lesions and standardization of reports.

Update of PSMA Theranostics in Prostate Cancer: Current Applications and Future Trends.

There is now an increasing trend for targeting cancers to go beyond early diagnosis and actually improve Progression-Free Survival and Overall Survival. Identifying patients who might benefit from a particular targeted treatment is the main focus for Precision Medicine. Radiolabeled ligands can be used as predictive biomarkers which can confirm target expression by cancers using positron emission tomography (PET). The same ligand can subsequently be labeled with a therapeutic radionuclide for targeted radionuclide therapy. This combined approach is termed "Theranostics". The prostate-specific membrane antigen (PSMA) has emerged as an attractive diagnostic and therapeutic target for small molecule ligands in prostate cancer. It can be labeled with either positron emitters for PET-based imaging or beta and alpha emitters for targeted radionuclide therapy. This review article summarizes the important concepts for Precision Medicine contributing to improved diagnosis and targeted therapy of patients with prostate cancer and we identify some key learning points and areas for further research.