A phase IIa trial of molecular radiotherapy with 177-lutetium DOTATATE in children with primary refractory or relapsed high-risk neuroblastoma.

PURPOSE: The objective of this phase IIa, open-label, single-centre, single-arm, two-stage clinical trial was to evaluate the safety and activity of 177-lutetium DOTATATE (LuDO) molecular radiotherapy in neuroblastoma. METHODS: Children with relapsed or refractory metastatic high-risk neuroblastoma were treated with up to four courses of LuDO. The administered activity was 75 to 100 MBq kg-1 per course, spaced at 8- to 12-week intervals. Outcomes were assessed by the International Neuroblastoma Response Criteria (primary outcome), progression-free survival (PFS), and overall survival (OS). RESULTS: The trial recruited 21 patients; eight received the planned four courses. There was dose-limiting haematologic toxicity in one case, but no other significant haematologic or renal toxicities. None of 14 evaluable patients had an objective response at 1 month after completion of treatment (Wilson 90% CI 0.0, 0.16; and 95% CI is 0.0, 0.22). The trial did not therefore proceed to the second stage. The median PFS was 2.96 months (95% CI 1.71, 7.66), and the median OS was 13.0 months (95% CI 2.99, 21.52). CONCLUSION: In the absence of any objective responses, the use of LuDO as a single agent at the dose schedule used in this study is not recommended for the treatment of neuroblastoma. There are several reasons why this treatment schedule may not have resulted in objective responses, and as other studies do show benefit, the treatment should not be regarded as being of no value. Further trials designed to overcome this schedule's limitations are required. TRIAL REGISTRATION: ISRCTN98918118; URL: https://www.isrctn.com/search?q=98918118.

Non-small-cell lung cancer resectability: diagnostic value of PET/MR.

PURPOSE: To assess the diagnostic performance of PET/MR in patients with non-small-cell lung cancer. METHODS: Fifty consecutive consenting patients who underwent routine (18)F-FDG PET/CT for potentially radically treatable lung cancer following a staging CT scan were recruited for PET/MR imaging on the same day. Two experienced readers, unaware of the results with the other modalities, interpreted the PET/MR images independently. Discordances were resolved in consensus. PET/MR TNM staging was compared to surgical staging from thoracotomy as the reference standard in 33 patients. In the remaining 17 nonsurgical patients, TNM was determined based on histology from biopsy, imaging results (CT and PET/CT) and follow-up. ROC curve analysis was used to assess accuracy, sensitivity and specificity of the PET/MR in assessing the surgical resectability of primary tumour. The kappa statistic was used to assess interobserver agreement in the PET/MR TNM staging. Two different readers, without knowledge of the PET/MR findings, subsequently separately reviewed the PET/CT images for TNM staging. The generalized kappa statistic was used to determine intermodality agreement between PET/CT and PET/MR for TNM staging. RESULTS: ROC curve analysis showed that PET/MR had a specificity of 92.3 % and a sensitivity of 97.3 % in the determination of resectability with an AUC of 0.95. Interobserver agreement in PET/MR reading ranged from substantial to perfect between the two readers (Cohen's kappa 0.646 - 1) for T stage, N stage and M stage. Intermodality agreement between PET/CT and PET/MR ranged from substantial to almost perfect for T stage, N stage and M stage (Cohen's kappa 0.627 - 0.823). CONCLUSION: In lung cancer patients PET/MR appears to be a robust technique for preoperative staging.

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.

Initial multicentre experience of high-speed myocardial perfusion imaging: comparison between high-speed and conventional single-photon emission computed tomography with angiographic validation.

PURPOSE: High-speed (HS) single-photon emission computed tomography (SPECT) with a recently developed solid-state camera shows comparable myocardial perfusion abnormalities to those seen in conventional SPECT. We aimed to compare HS and conventional SPECT images from multiple centres with coronary angiographic findings. METHODS: The study included 50 patients who had sequential conventional SPECT and HS SPECT myocardial perfusion studies and coronary angiography within 3 months. Stress and rest perfusion images were visually analysed and scored semiquantitatively using a 17-segment model by two experienced blinded readers. Global and coronary territorial summed stress scores (SSS) and summed rest scores (SRS) were calculated. Global SSS ≥3 or coronary territorial SSS ≥2 was considered abnormal. In addition the total perfusion deficit (TPD) was automatically derived. TPD >5% and coronary territorial TPD ≥3% were defined as abnormal. Coronary angiograms were analysed for site and severity of coronary stenosis; ≥50% was considered significant. RESULTS: Of the 50 patients, 13 (26%) had no stenosis, 22 (44%) had single-vessel disease, 6 (12%) had double-vessel disease and 9 (18%) had triple-vessel disease. There was a good linear correlation between the visual global SSS and SRS (Spearman's ρ 0.897 and 0.866, respectively; p < 0.001). In relation to coronary angiography, the sensitivities, specificities and accuracies of HS SPECT and conventional SPECT by visual assessment were 92% (35/38), 83% (10/12) and 90% (45/50) vs. 84% (32/38), 50% (6/12) and 76% (38/50), respectively (p < 0.001). The sensitivities, specificities and accuracies of HS SPECT and conventional SPECT in relation to automated TPD assessment were 89% (31/35), 57% (8/14) and 80% (39/49) vs. 86% (31/36), 77% (10/13) and 84% (41/49), respectively. CONCLUSION: HS SPECT allows fast acquisition of myocardial perfusion images that correlate well with angiographic findings with overall accuracy by visual assessment better than conventional SPECT. Further assessment in a larger patient population may be needed to confirm this observation.

Identifying and troubleshooting the pitfalls of ictal/interictal brain perfusion SPECT studies.

Epilepsy is a prevalent condition, and surgical intervention can benefit patients with refractory seizures. Single photon emission computed tomography (SPECT) using 99mTc-HMPAO or 99mTc-ECD provides assessment of regional cerebral blood flow and is the primary non-invasive approach for imaging brain perfusion in ictal and interictal states. Ictal/interictal SPECT is valuable in localising epileptogenic foci, particularly when MRI and electroencephalography are negative. However, to obtain accurate images reflecting brain perfusion in both states, meticulous preparation of the patient, timely radiotracer injection and close coordination between neurology and nuclear medicine teams are essential. Tracers also have inherent limitations, and patients may present with coexisting brain pathologies for which coregistration of SPECT images with MRI is recommended to improve diagnostic accuracy. Inconclusive SPECT findings may require repeating the exam or considering additional investigations. A comprehensive approach, considering various factors, is crucial for accurate interpretation of SPECT studies in presurgical epilepsy evaluations. This article provides a summary of the organisation and key challenges involved in conducting ictal/interictal SPECT studies, covering the entire process from a patient's hospital arrival to the integration of results within their presurgical pathway and using our experience of 182 patients over 10 years.

Prognostic role of PET scanning before and after reduced-intensity allogeneic stem cell transplantation for lymphoma.

Allogeneic stem cell transplantation (SCT) is an established therapy for patients with relapsed lymphoma, but the role of positron emission tomography (PET) scanning preallogeneic and postallogeneic SCT is uncertain. We investigated whether pretransplantation PET status predicted outcome after allogeneic SCT and whether PET surveillance after transplantation provided additional information compared with computed tomography (CT) scanning. Eighty consecutive patients with lymphoma who received a reduced-intensity allogeneic SCT were entered onto a prospective trial. PET and CT scans were performed before transplantation and up to 36 months after transplantation. Forty-two patients were PET-positive before transplantation. Pretransplantation PET status had no significant impact on either relapse rate or overall survival. Thirty-four relapses were observed, of which 17 were PET-positive with a normal CT scan at relapse. Donor lymphocyte infusion (DLI) was administered in 26 episodes of relapse and was guided by PET alone in 14 patients. These findings suggest that, in contrast to autologous SCT, pretransplantation PET status is not predictive of relapse and survival after allogeneic SCT for lymphoma. Posttransplantation surveillance by PET detected relapse before CT in half of episodes, often allowing earlier administration of DLI in patients with recurrent lymphoma, and permitted withholding of potentially harmful DLI in those with PET-negative masses on CT scans.

¹¹¹In-DTPA°-octreotide (Octreoscan), ¹³¹I-MIBG and other agents for radionuclide therapy of NETs.

This paper is a critical review of the literature on NET radionuclide therapy with (111)In-DTPA(0)-octreotide (Octreoscan) and (131)I-MIBG, focusing on efficacy and toxicity. Some potential future applications and new candidate therapeutic agents are also mentioned. Octreoscan has been a pioneering agent for somatostatin receptor radionuclide therapy. It has achieved symptomatic responses and disease stabilization, but it is now outperformed by the corresponding ß-emitter agents (177)Lu-DOTATATE and (90)Y-DOTATOC. (131)I-MIBG is the radionuclide therapy of choice for inoperable or metastatic phaeochromocytomas/paragangliomas, which avidly concentrate this tracer via the noradrenaline transporter. Symptomatic, biochemical and tumour morphological response rates of 50-89%, 45-74% and 27-47%, respectively, have been reported. (131)I-MIBG is a second-line radiopharmaceutical for treatment of enterochromaffin carcinoids, mainly offering the benefit of amelioration of hormone-induced symptoms. High specific activity, non-carrier-added (131)I-MIBG and meta-astato((211)At)-benzylguanidine (MABG) are tracers with potential for enhanced therapeutic efficacy, yet their integration into clinical practice awaits further exploration. Amongst other promising agents, radiolabelled exendin analogues show potential for imaging and possibly therapy of insulinomas, while preclinical studies are currently evaluating DOTA peptides targeting the CCK-2/gastrin receptors that are overexpressed by medullary thyroid carcinoma cells.

Hypertension complicating 131I-meta-iodobenzylguanidine therapy for neuroblastoma.

PURPOSE: Radiolabelled meta-iodobenzylguanidine (mIBG), used as targeted therapy for neuroblastoma, is known to have effects on blood pressure (BP). In this study we audited BP changes in patients receiving (131)I-mIBG therapy for neuroblastoma to identify BP-related adverse events (AE) and possible predictive factors. METHODS: Between 2003 and 2010, 50 patients with neuroblastoma received 110 (131)I-mIBG administrations. BP measurements before and after administration were compared with age- and sex-matched centile values. AE were analysed, and possible predisposing factors identified. RESULTS: This population had a baseline BP distribution higher than that of their age- and sex-matched peers, with 16% of preadministration systolic BP values above the 95th centile. Changes in BP after administration showed an approximately normal distribution with similar numbers of reduced and increased values. Four AE, all related to hypertension, occurred with one patient having generalized seizures. One AE was immediate, others occurred between 20 and 25 h after administration. No significant association between AE and patient age or sex was demonstrated. However, a significant association between AE and high preadministration BP was shown, both above the 90th centile (p = 0.0022) and above the 95th centile (p = 0.0135). CONCLUSION: Clinically relevant hypertension following (131)I-mIBG therapy affected less than 5% of administrations, but was more common in those patients with preexisting hypertension. As hypertensive episodes may occur many hours after treatment, close monitoring of BP needs to be continued for at least 48 h after administration of (131)I-mIBG.

The Impact of COVID-19 on Nuclear Medicine in Europe.

The COVID-19 pandemic has profoundly changed hospital activities, including nuclear medicine (NM) practice. This review aimed to determine and describe the impact of COVID-19 on NM in Europe and critically discuss actions and strategies applied to face the pandemic. A literature search for relevant articles was performed on PubMed, covering COVID-19 studies published up until January 21, 2021. The findings were summarized according to general and specific activities within the NM departments. The pandemic strongly challenged NM departments: a reduction in the workforce has been experienced in almost every center in Europe due to personnel diagnosed with COVID-19 and other reasons related to the coronavirus. NM departments introduced procedures to limit COVID-19 transmission, including environmental and personal hygiene, social distancing, rescheduling of non-high-priority procedures, the correct use of personal protective equipment, and prompt identification of suspect COVID-19 cases. A proportion of the departments experienced a delay in radiopharmaceuticals supply or technical assistance during the pandemic. Furthermore, the pandemic resulted in a significant reduction of diagnostic and therapeutic NM procedures, as well as a reduced level of care for patients affected by diseases other than COVID-19, such as cancer or acute cardiovascular disease. Telemedicine services have been set up to maintain medical assistance for patients. COVID-19 pandemic has reshaped human work resources, patient's diagnostic and therapeutic management, operative models, radiopharmaceutical supplies, teaching, training and research of NM departments. Limits of availability of resources emerged. Nonetheless, we have to provide continuity in care, especially for fragile patients, maintaining infection control measures. Challenges that have been faced should reshape our vision and get us prepared for the future.

Renal protection during 177lutetium DOTATATE molecular radiotherapy in children: a proposal for safe amino acid infusional volume during peptide receptor radionuclide therapy.

Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues such as 177-lutetium DOTATATE is an effective treatment modality for neuroendocrine tumours, paragangliomas, and neuroblastomas. However, renal and haematopoietic toxicities are the major limitations of this therapeutic approach. The renal toxicity of PRRT is mediated by renal proximal tubular reabsorption and interstitial retention of the radiolabelled peptides resulting in excessive renal irradiation that can be dose-limiting. To protect the kidneys from PRRT-induced radiation nephropathy, basic amino acids are infused during PRRT as they competitively bind to the proximal tubular cells and prevent uptake of the radionuclide. In adults, 1 L of a basic amino acid solution consisting of arginine and lysine is infused over 4 h commencing 30 min prior to PRRT. However, this volume of amino acids infused over 4 h is excessive in small children and can result in hemodynamic overload. This is all the more relevant in paediatric oncology, as many of the children may have been heavily pretreated and so may have treatment-related renal and or cardiac impairment. We have therefore developed the following guidelines for safe paediatric dosing of renal protective amino acid infusions during PRRT. Our recommendations have been made taking into consideration the renal physiology in small children and the principles of safe fluid management in children.

The value of [68Ga]Ga-DOTA-TATE PET/CT in diagnosis and management of suspected pituitary tumors.

BACKGROUND: Gallium 68-tetraazacyclododecane-tetraacetic acid-octreotate ([68Ga]Ga-DOTA-TATE) is a selective somatostatin analogue ligand, which shows increased affinity for somatostatin receptor subtype (SSTR) 2 and has been used routinely for imaging neuroendocrine tumors with PET/CT. We investigated the utility of [68Ga]Ga-DOTA-TATE positron emission tomography/computed tomography (PET/CT) in patients with suspected pituitary pathology. We reviewed imaging for twenty consecutive patients (8 men, 12 women, mean age of 48.2, range 14-78) with suspected pituitary pathology who were referred for [68Ga]Ga-DOTA-TATE PET/CT. RESULTS: Nine patients presented with recurrent Cushing's syndrome following surgical resection of pituitary adenomas due to recurrent Cushing's disease (seven patients) and ectopic ACTH secreting tumor (2 patients). All seven patients with recurrent Cushing's disease showed positive pituitary [68Ga]Ga-DOTA-TATE uptake while both cases of ectopic hormonal secretion had absented pituitary uptake. In 1 of these 2 patients, [68Ga]Ga-DOTA-TATE was able to localize the source of ectopic ACTH tumor. Six patients presented de novo with Cushing's due to ectopic ACTH secretion; [68Ga]Ga-DOTA-TATE PET/CT was able to localize ectopic tumors in six of eight patients (3 lungs, 2 pancreases, 1 mid-gut) There was high uptake [68Ga]Ga-DOTA-TATE in 3 cases of recurrent central hyperthyroidism (SUVmax 6.6-14.3) and 2 cases of prolactinoma (SUVmax 5.5 and 11.3). CONCLUSION: Absent [68Ga]Ga-DOTA-TATE activity in the pituitary fossa is useful in excluding pituitary disease in recurrent Cushing's. Recurrent pituitary thyrotropinomas and prolactinomas showed moderate to high pituitary activity. In addition, in Cushing's syndrome, [68Ga]Ga-DOTA-TATE is useful for detection of ectopic sources of ACTH production, especially where anatomic imaging is negative.

Radiomics-Based Texture Analysis of 68Ga-DOTATATE Positron Emission Tomography and Computed Tomography Images as a Prognostic Biomarker in Adults With Neuroendocrine Cancers Treated With 177Lu-DOTATATE.

PURPOSE: Neuroendocrine tumors (NET) are rare cancers with variable behavior. A better understanding of prognosis would aid individualized management. The aim of this hypothesis-generating pilot study was to investigate the prognostic potential of tumor heterogeneity and tracer avidity in NET using texture analysis (TA) of 68Ga-DOTATATE positron emission tomography (PET) and non-enhanced computed tomography (CT) performed at baseline in patients treated with 177Lu-DOTATATE. It aims to justify a larger-scale study to evaluate its clinical value. METHODS: The pretherapy 68Ga-DOTATATE PET-CT scans of 44 patients with metastatic NET (carcinoid, pancreatic, thyroid, head and neck, catecholamine-secreting, and unknown primary NET) treated with 177Lu-DOTATATE were analyzed retrospectively using commercially available texture analysis research software. Image filtration extracted and enhanced objects of different sizes (fine, medium, coarse), then quantified heterogeneity by statistical and histogram-based parameters (mean intensity, standard deviation, entropy, mean of positive pixels, skewness, and kurtosis). Regions of interest were manually drawn around up to five of the most 68Ga-DOTATATE avid lesions for each patient. 68Gallium uptake on PET was quantified as SUVmax and SUVmean. Associations between imaging and clinical markers with progression-free (PFS) and overall survival (OS) were assessed using univariate Kaplan-Meier analysis. Independence of the significant univariate markers of survival was tested using multivariate Cox regression analysis. RESULTS: Measures of heterogeneity (higher kurtosis, higher entropy, and lower skewness) on coarse-texture scale CT and unfiltered PET images predicted shorter PFS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness: p=0.03) and shorter OS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness p=0.02). Conventional PET parameters such as SUVmax and SUVmean showed trends towards predicting outcome but were not statistically significant. Multivariate analysis identified that CT-TA (coarse kurtosis: HR=2.57, 95% CI=1.22-5.38, p=0.013) independently predicted PFS, and PET-TA (unfiltered skewness: HR=9.05, 95% CI=1.19-68.91, p=0.033) independently predicted OS. CONCLUSION: These preliminary data generate a hypothesis that radiomic analysis of neuroendocrine cancer on 68Ga-DOTATATE PET-CT may be of prognostic value and a valuable addition to the assessment of patients.

Distinct Patterns of Brain Metabolism in Patients at Risk of Sudden Unexpected Death in Epilepsy.

Objective: To characterize regional brain metabolic differences in patients at high risk of sudden unexpected death in epilepsy (SUDEP), using fluorine-18-fluorodeoxyglucose positron emission tomography (18FDG-PET). Methods: We studied patients with refractory focal epilepsy at high (n = 56) and low (n = 69) risk of SUDEP who underwent interictal 18FDG-PET as part of their pre-surgical evaluation. Binary SUDEP risk was ascertained by thresholding frequency of focal to bilateral tonic-clonic seizures (FBTCS). A whole brain analysis was employed to explore regional differences in interictal metabolic patterns. We contrasted these findings with regional brain metabolism more directly related to frequency of FBTCS. Results: Regions associated with cardiorespiratory and somatomotor regulation differed in interictal metabolism. In patients at relatively high risk of SUDEP, fluorodeoxyglucose (FDG) uptake was increased in the basal ganglia, ventral diencephalon, midbrain, pons, and deep cerebellar nuclei; uptake was decreased in the left planum temporale. These patterns were distinct from the effect of FBTCS frequency, where increasing frequency was associated with decreased uptake in bilateral medial superior frontal gyri, extending into the left dorsal anterior cingulate cortex. Significance: Regions critical to cardiorespiratory and somatomotor regulation and to recovery from vital challenges show altered interictal metabolic activity in patients with frequent FBTCS considered to be at relatively high-risk of SUDEP, and shed light on the processes that may predispose patients to SUDEP.

Pediatric and adolescent lymphoma: comparison of whole-body STIR half-Fourier RARE MR imaging with an enhanced PET/CT reference for initial staging.

PURPOSE: To compare the diagnostic performance of rapid whole-body anatomic magnetic resonance (MR) staging of pediatric and adolescent lymphoma to an enhanced positron emission tomographic (PET)/computed tomographic (CT) reference standard. MATERIALS AND METHODS: Ethical permission was given by the University College London Hospital ethics committee, and informed written consent was obtained from all participants and/or parents or guardians. Thirty-one subjects (age range, 7.3-18.0 years; 18 male, 11 female) with histologically proved lymphoma were prospectively recruited. Pretreatment staging was performed with whole-body short inversion time inversion-recovery (STIR) half-Fourier rapid acquisition with relaxation enhancement (RARE) MR imaging, fluorine 18 fluorodeoxyglucose PET/CT, and contrast agent-enhanced chest CT. Twenty-six subjects had posttreatment PET/CT and compromised our final cohort. Eleven nodal and 11 extranodal sites per patient were assessed on MR imaging by two radiologists in consensus, with a nodal short-axis threshold of >1 cm and predefined extranodal positivity criteria. The same sites were independantly evaluated by two nuclear medicine physicians on PET/CT images. Disease positivity was defined as a maximum standardized uptake value >2.5 or nodal size >1 cm. An unblinded expert panel reevaluated the imaging findings, removing perceptual errors, and derived an enhanced PET/CT reference standard (taking into account chest CT and 3-month follow-up imaging) against which the reported and intrinsic performance of MR imaging was assessed by using the kappa statistic. RESULTS: There was very good agreement between MR imaging and the enhanced PET/CT reference standard for nodal and extranodal staging (kappa = 0.96 and 0.86, respectively) which improved following elimination of perceptual errors (kappa = 0.97 and 0.91, respectively). The sensitivity and specificity of MR imaging (following removal of perceptual error) were 98% and 99%, respectively, for nodal disease and 91% and 99%, respectively, for extranodal disease. CONCLUSION: Whole-body STIR half-Fourier RARE MR imaging of pediatric and adolescent lymphoma can accurately depict nodal and extranodal disease and may provide an alternative nonionizing imaging method for anatomic disease assessment at initial staging.

Comparison of (68)Ga-DOTATATE and (18)F-fluorodeoxyglucose PET/CT in the detection of recurrent medullary thyroid carcinoma.

PURPOSE: This was a retrospective study to detect and map the extent of disease in recurrent medullary thyroid carcinoma (MTC) using the novel PET somatostatin analogue (68)Ga-DOTATATE and conventional (18)F-FDG positron emission tomography/computed tomography (PET/CT). METHODS: Eighteen patients (13 men, 5 women, median age: 54 years) who had previously been operated on for MTC and presented with biochemical (raised calcitonin levels) and/or imaging evidence of recurrence underwent both (68)Ga-DOTATATE and (18)F-FDG PET/CT within a maximum interval of 4 weeks (median interval of 1 week). (68)Ga-DOTATATE- and (18)F-FDG-avid lesions were recorded per patient as well as per region in six distinct regions: (1) thyroid bed-local recurrence, (2) cervical lymph nodes, (3) mediastinum, (4) lungs, (5) liver and (6) bones. The (68)Ga-DOTATATE and (18)F-FDG PET/CT findings were classified as positive or negative on visual interpretation. These findings were further characterised as concordant or discordant, depending on whether there was agreement or discrepancy in imaging with the two radiotracers. A separate analysis of the unenhanced CT component of the examination was performed. Verification of the lesions was achieved by histopathological analysis, further imaging studies and clinical follow-up. RESULTS: (68)Ga-DOTATATE PET/CT imaging achieved disease detection in 13 of 18 and (18)F-FDG PET/CT in 14 of 18 patients. These results corresponded to per-patient sensitivities of 72.2% [95% confidence interval (CI): 46.4-89.3%] for (68)Ga-DOTATATE versus 77.8% (95% CI: 51.9-92.6%) for (18)F-FDG (non-significant difference). (18)F-FDG revealed a total of 28 metastatic MTC regions and (68)Ga-DOTATATE 23 regions. In ten patients a discordant tracer pattern of per-region and/or per-lesion distribution of recurrent disease was observed, while in four patients a concordant pattern was noted (no lesions were detected by either modality in the remaining four patients). CONCLUSION: Neither (18)F-FDG nor (68)Ga-DOTATATE PET/CT can fully map the extent of disease in patients with recurrent MTC, although (18)F-FDG PET/CT may identify more lesions. However, (68)Ga-DOTATATE PET/CT can be a useful complementary imaging tool and may identify patients suitable for consideration of targeted radionuclide somatostatin analogue therapy.

Procedure guidelines for PET/CT tumour imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE.

The aim of these guidelines is to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin (SST) receptor PET/CT imaging using 68Ga-DOTA-conjugated peptides, analogues of octreotide, that bind to SST receptors. This imaging modality should not be regarded as the only approach to visualizing tumours expressing SST receptors or as excluding other imaging modalities useful for obtaining comparable results. The corresponding guidelines of 111In-pentetreotide scintigraphy imaging have been considered and partially integrated with this text. The same has been done with the relevant and recent literature in this field and the final result has been discussed by distinguished experts.

68Ga-DOTATATE and 123I-mIBG as imaging biomarkers of disease localisation in metastatic neuroblastoma: implications for molecular radiotherapy.

PURPOSE: Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) and lutetium-177-labelled DOTATATE (Lu-DOTATATE) are used for molecular radiotherapy of metastatic neuroblastoma. These are taken up by the noradrenaline transporter (NAT) and the somatostatin receptor subtype 2 (SSTR-2), respectively. Scintigraphy of iodine-123-labelled meta-iodobenzylguanidine (I-mIBG) and gallium-68 DOTATATE (Ga-DOTATATE) PET are used to select patients for therapy. These demonstrate the extent and location of tumour, and avidity of uptake by cells expressing NAT and SSTR-2, respectively. This study compared the similarities and differences in the anatomical distribution of these two imaging biomarkers in an unselected series of patients with metastatic neuroblastoma undergoing assessment for molecular radiotherapy. METHODS: Paired whole-body planar I-mIBG views and Ga-DOTATATE maximum intensity projection PET scans of metastatic neuroblastoma patients were visually compared. The disease extent was assessed by a semiquantitative scoring method. RESULTS: Paired scans from 42 patients were reviewed. Ga-DOTATATE scans were positive in all patients, I-mIBG scans were negative in two. In two patients, there was a mismatch, with some lesions identified only on the I-mIBG scan, and others visible only on the Ga-DOTATATE scan. CONCLUSION: Ga-DOTATATE and I-mIBG scans yield complementary information. For a more comprehensive assessment, consideration could be given to the use of both I-mIBG and Ga-DOTATATE imaging scans. Because of the heterogeneity of distribution of molecular targets revealed by these techniques, a combination of both I-mIBG and Lu-DOTATATE molecular radiotherapy may possibly be more effective than either alone.

Personalisation of Molecular Radiotherapy through Optimisation of Theragnostics.

Molecular radiotherapy, or targeted radionuclide therapy, uses systemically administered drugs bearing a suitable radioactive isotope, typically a beta emitter. These are delivered via metabolic or other physiological pathways to cancer cells in greater concentrations than to normal tissues. The absorbed radiation dose in tumour deposits causes chromosomal damage and cell death. A partner radiopharmaceutical, most commonly the same vector labelled with a different radioactive atom, with emissions suitable for gamma camera or positron emission tomography imaging, is used to select patients for treatment and to assess response. The use of these pairs of radio-labelled drugs, one optimised for therapy, the other for diagnostic purposes, is referred to as theragnostics. Theragnostics is increasingly moving away from a fixed number of defined activity administrations, to a much more individualised or personalised approach, with the aim of improving treatment outcomes, and minimising toxicity. There is, however, still significant scope for further progress in that direction. The main tools for personalisation are the following: imaging biomarkers for better patient selection; predictive and post-therapy dosimetry to maximise the radiation dose to the tumour while keeping organs at risk within tolerance limits; imaging for assessment of treatment response; individualised decision making and communication about radiation protection, adjustments for toxicity, inpatient and outpatient care.