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.

Changes in the global impact of COVID-19 on nuclear medicine departments during 2020: an international follow-up survey.

AIM: As a follow-up to the international survey conducted by the International Atomic Energy Agency (IAEA) in April 2020, this survey aims to provide a situational snapshot of the COVID-19 impact on nuclear medicine services worldwide, 1 year later. The survey was designed to determine the impact of the pandemic at two specific time points: June and October 2020, and compare them to the previously collected data. MATERIALS AND METHODS: A web-based questionnaire, in the same format as the April 2020 survey was disseminated to nuclear medicine facilities worldwide. Survey data was collected using a secure software platform hosted by the IAEA; it was made available for 6 weeks, from November 23 to December 31, 2020. RESULTS: From 505 replies received from 96 countries, data was extracted from 355 questionnaires (of which 338 were fully completed). The responses came from centres across varying regions of the world and with heterogeneous income distributions. Regional differences and challenges across the world were identified and analysed. Globally, the volume of nuclear medicine procedures decreased by 73.3% in June 2020 and 56.9% in October 2020. Among the nuclear medicine procedures, oncological PET studies showed less of a decline in utilization compared to conventional nuclear medicine, particularly nuclear cardiology. The negative impact was also significantly less pronounced in high-income countries. A trend towards a gradual return to the pre-COVID-19 situation of the supply chains of radioisotopes, generators, and other essential materials was evident. CONCLUSION: The year 2020 has a significant decrease in nuclear medicine diagnostic and therapeutic procedures as a result of the pandemic-related challenges. In June, the global decline recorded in the survey was greater than in October when the situation began to show improvement. However, the total number of procedures remained below those recorded in April 2020 and fell to less than half of the volumes normally carried out pre-pandemic.

Characterizing the alkaptonuria joint and spine phenotype and assessing the effect of homogentisic acid lowering therapy in a large cohort of 87 patients.

A large alkaptonuria (AKU) cohort was studied to better characterize the poorly understood spondyloarthropathy of rare disease AKU. Eighty-seven patients attended the National Alkaptonuria Centre (NAC) between 2007 and 2020. Seven only attended once. Fifty-seven attended more than once and received nitisinone 2 mg daily. Twenty-three attended at least twice without receiving nitisinone. Assessments included questionnaire analysis, 18F Positron emission tomography computerised tomography (PETCT), as well as photographs of ochronotic pigment in eyes and ears at baseline when 2 mg nitisinone was commenced and yearly thereafter. Blood and urine samples were collected for chemical measurement. The prevalence of ochronosis, as well as pain, PETCT and combined pain and PETCT scores, was greatly increased at 90.5%, 85.7%, 100%, and 100%, respectively. Joint pain scores were greatest in proximal joints in upper and lower limbs. PETCT joint scores were higher in proximal joints in upper limb but higher in distal joints in the lower limb. Spine pain scores were highest in lumbar, followed by cervical, thoracic, and cervical regions at 77.4%, 59.5%, 46.4%, and 25%, respectively. PETCT spine scores were highest in thoracic followed by lumbar, cervical, and sacroiliac regions at 74.4%, 70.7%, 64.6%, and 47.8% respectively; ochronosis associated closely with spondyloarthropathy scores (R = .65; P < .0001). Nitisinone reversed ochronosis significantly, with a similar pattern of decreased joint and spine disease. Spondyloarthropathy is a highly prevalent feature in this NAC cohort. Ochronosis appears to be associated with spondyloarthropathy. Nitisinone decreases ochronosis and had a similar nonsignificant effect pattern on spondyloarthropathy.

Characterising the arthroplasty in spondyloarthropathy in a large cohort of eighty-seven patients with alkaptonuria.

Arthroplasty in the spondyloarthropathy (SPOND) of alkaptonuria (AKU) in incompletely characterised. The aim was to improve the understanding of arthroplasty in AKU through a study of patients attending the National Alkaptonuria Centre (NAC). Eighty-seven patients attended the NAC between 2007 and 2020. Seven only attended once. Fifty-seven attended more than once and received nitisinone 2 mg daily. Twenty-three attended at least twice without receiving nitisinone. Assessments including questionnaire analysis eliciting details of arthroplasty and other surgical treatments for SPOND, 18 FPETCT and CT densitometry at the neck of hip and lumbar spine, as well as photographs of the eyes and ears were acquired from patients attending the National Alkaptonuria Centre (NAC) at baseline when 2 mg nitisinone was commenced, and yearly thereafter. Photographs were scored to derive ochronosis scores. Blood and urine samples were collected for chemical analyses. The prevalence of arthroplasty was 36.8%, similar in males and females, occurring especially in the knees, hips and shoulders. Multiple arthroplasties were found in 29 patients (33.3%) in this cohort. Incident arthroplasty was 6.5% in the nitisinone group and 7.1% in the no-nitisinone group. Incident arthroplasty was 11.3% in the group with baseline arthroplasty and 3.51% in the group without. A strong association of arthroplasty with SPOND (R = 0.5; P << .0001) and ochronosis (R = 0.54; P < .0001) was seen. Nitisinone had no significant effect on incident arthroplasty. Arthroplasty due to ochronosis and SPOND is common in AKU. Nitisinone decreased ochronosis but had no effect on arthroplasty in this cohort.

PET/CT features of extrapulmonary tuberculosis at first clinical presentation: a cross-sectional observational 18F-FDG imaging study across six countries.

BACKGROUND: A large proportion of the huge global burden of extrapulmonary tuberculosis (EPTB) cases are treated empirically without accurate definition of disease sites and extent of multi-organ disease involvement. Positron emission tomography (PET) imaging using 2-deoxy-2-(fluorine-18) fluoro-d-glucose (18F-FDG) in tuberculosis could be a useful imaging technique for localising disease sites and extent of disease. METHODS: We conducted a study of HIV-negative adult patients with a new clinical diagnosis of EPTB across eight centres located in six countries: India, Pakistan, Thailand, South Africa, Serbia and Bangladesh, to assess the extent of disease and common sites involved at first presentation. 18F-FDG PET/computed tomography (CT) scans were performed within 2 weeks of presentation. FINDINGS: 358 patients with EPTB (189 females; 169 males) were recruited over 45 months, with an age range of 18-83 years (females median 30 years; males median 38 years). 350 (98%) out of 358 patients (183 female, 167 male) had positive scans. 118 (33.7%) out of 350 had a single extrapulmonary site and 232 (66.3%) out of 350 had more than one site (organ) affected. Lymph nodes, skeleton, pleura and brain were common sites. 100 (28%) out of 358 EPTB patients had 18F-FDG PET/CT-positive sites in the lung. 110 patients were 18F-FDG PET/CT-positive in more body sites than were noted clinically at first presentation and 160 patients had the same number of positive body sites. INTERPRETATION: 18F-FDG PET/CT scan has potential for further elucidating the spectrum of disease, pathogenesis of EPTB and monitoring the effects of treatment on active lesions over time, and requires longitudinal cohort studies, twinned with biopsy and molecular studies.

Radium-223 dichloride in prostate cancer: proof of principle for the use of targeted alpha treatment in clinical practice.

PURPOSE: To summarise data with radium-223 dichloride (223RaCl2), a mechanism-mediated targeted alpha therapy (TAT), in metastatic castration-resistant prostate cancer (mCRPC) and to chart the development of TAT in mCRPC and in other tumour types. METHODS: Literature for this systematic review was identified using a PubMed search: ("targeted alpha therapy" or "targeted alpha particle therapy") or (213-bismuth or bismuth-213 or 213Bi) or (225-actinium or actinium-225 or 225Ac) or (211-astatine or astatine-211 or 211At) or (212-lead or lead-212 or 212Pb) or (227-thorium or thorium-227 or 227Th) or (223-radium or radium-223 or 223Ra or alpharadin) and (malignancy or cancer). Results were limited to English-language publications in humans, with the article type "clinical trial". RESULTS: Forty-one publications were included (30 from the literature search and 11 from manual searches/reviews). In clinical trials in mCRPC, 223RaCl2 monotherapy is well tolerated, with significantly longer overall survival than placebo and improved quality of life. Clinical trial data have been reinforced by findings from real-world studies. 223RaCl2 has also shown promise in other tumour types with bone metastases, including advanced breast cancer and advanced renal cell carcinoma (in combination with anti-vascular endothelial growth factor). Several astatine-211- and bismuth-213-labelled molecules have demonstrated anti-tumour activity and acceptable toxicity in other tumour types. CONCLUSIONS: 223RaCl2 has demonstrated "proof of concept" for use of TAT in cancer in clinical practice. The efficacy and safety of 223RaCl2 monotherapy have been demonstrated in mCRPC, and 223RaCl2 combination therapies are under investigation in various tumours. TAT has broad applicability across tumour types.

Sequential 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scan findings in patients with extrapulmonary tuberculosis during the course of treatment-a prospective observational study.

BACKGROUND: Initial studies of tuberculosis (TB) in macaques and humans using 18F-FDG positron emission tomography (PET) imaging as a research tool suggest its usefulness in localising disease sites and as a clinical biomarker. Sequential serial scans in patients with extrapulmonary TB (EPTB) could inform on the value of PET-CT for monitoring response to treatment and defining cure. PATIENTS AND METHODS: HIV-negative adults with EPTB from eight sites across six countries had three 18F-FDG PET/CT scans: (i) within 2 weeks of enrolment, (ii) at 2 months into TB treatment and (iii) at end of ATT treatment. Scanning was performed according to the EANM guidelines. 18F-FDG PET/CT scans were performed 60 ± 10 min after intravenous injection of 2.5-5.0 MBq/kg of 18F-FDG. FINDINGS: One hundred and forty-seven patients with EPTB underwent 3 sequential scans. A progressive reduction over time of both the number of active sites and the uptake level (SUVmax) at these sites was seen. At the end of WHO recommended treatment, 53/147 (36.0%) patients had negative PET/CT scans, and 94/147 (63.9%) patients remained PET/CT positive, of which 12 patients had developed MDR TB. One died of brain tuberculoma. INTERPRETATION: Current 18F-FDG PET/CT imaging technology cannot be used clinically as a biomarker of treatment response, cure or for decision-making on when to stop EPTB treatment. PET/CT remains a research tool for TB and further development of PET/CT is required using new Mycobacterium tuberculosis-specific radiopharmaceuticals targeting high-density surface epitopes, gene targets or metabolic pathways.

68Gallium DOTANOC-PET Imaging in Lung Carcinoids: Impact on Patients' Management.

BACKGROUND: 68Gallium DOTA-PET imaging is preferable to standard somatostatin receptor scintigraphy where available; however, its role in the management of lung carcinoid tumours (LC) remains unclear. METHODS: All consecutive patients with histologically confirmed LC from two ENETS Centres of Excellence were identified retrospectively. The primary objective was to assess the impact of 68Ga-DOTANOC-PET on clinical management in patients with LC. RESULTS: Of 166 patients screened, 46 were eligible: 52% female, median age 57 years (range 21-86); type of LC: diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (4%), typical (44%), atypical (35%), not reported (17%); stage: localised (63%), locally advanced (13%), and metastatic (17%) (7% unknown). A total of 47 68Ga-DOTANOCs were performed with the following rationale: LC diagnosis confirmation (4; 9%), primary tumour identification (2; 4%), post-surgical assessment (19; 40%), staging (patients with known LC present at time of 68Ga-DOTANOC) (19; 40%), and consideration of peptide receptor radionuclide therapy (3; 7%). Twenty-seven (57%) scans showed evidence of non-physiological uptake: median maximum standardised uptake value 7.2 (range 1.42-53). 68Ga-DOTANOC provided additional information in 37% (95% CI 22-51) of patients and impacted on management in 26% (95% CI 12-41); 9 patients (21%) were identified to have occult sites of metastases. Out of the 19 patients with post-surgical 68Ga-DOTANOC, 3 (16%) were identified to have distant metastases. There were no differences in the rate of practice changing 68Ga-DOTANOC results by type of LC (p value 0.5). CONCLUSIONS: Our results support the role of 68Ga-DOTANOC for optimising the management of patients with LC, including post-surgical re-staging due to the potential for identifying occult metastases.

Skeletal Metastases and Benign Mimics on NaF PET/CT: A Pictorial Review.

OBJECTIVE: The aim of this article is to present examples in which sodium fluoride labelled with 18F (NaF) bone PET/CT would be a useful adjunct to guide complex clinical decisions about the staging, restaging, and treatment approach for patients with skeletal metastases and benign causes of NaF activity that can be mistaken for bone metastases. We present a pictorial review of selected cases of this cohort of patients. CONCLUSION: NaF PET/CT hybrid fusion imaging is extremely useful in identifying potential causes of pain in patients with malignancies that have an affinity for skeletal metastases. This technique can help detect bone metastases, in problem solving, and to direct appropriate management.

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.

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.

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.

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.

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.

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.

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.

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.