Methods to assess the biodistribution of radiolabelled somatostatin analogues and treatment response of neuroendocrine tumours.

Introduction: During the past decade, proof of the principle that somatostatin receptors can be successfully used for in vivo targeting of neuroendocrine tumours (NETs) has been provided. These tumours are imaged with 111Indium-pentetreotide and treated with 90Yttrium labeled somatostatin analogues. The aim of this study was to assess (a) the biodistribution and residency of 90Y labelled agents using the brehmsstrahlung imaging technique (b) the tumour response to various treatment modalities using a simplified scintigraphic method [Functional SPECT tumour volume (STV)]. Material and methods: 1) 19 patients with NETs were imaged with 111In-pentetreotide and 14 of them underwent treatment with 90Y-lanreotide. The rest underwent treatment with 90Y-SMT. All the patients were imaged 24 hours post-therapy. Brehmsstrahlung images obtained post therapies were used to assess the 90Y-lanreotide biodistribution in 14 patients and the 5 patients treated with 90Y-SMT, comparing them with 111In-pentetreotide. 2) In 42 patients with NETs a retrospective analysis was performed of the 111In-pentetreotide imaging and CT scan in patients treated with different therapies. A simplified scintigraphic method using 111In-pentetreotide SPECT liver imaging was used to monitor changes in tumour response and to determine how this correlates with CT scan and clinical response. Results: 1) 90Y-lanreotide and 90Y-SMT (with amino acids) have much lower uptake in the kidney (p 0.000 and 0.041 respectively) than 111In-pentetreotide. G Gnanasegaran MD 2 2) 22/42 patients had a good clinical response. A mean fall in total functional STV of 37% was seen in patients with symptomatic relief and a mean increase of 72 % was seen in patients with no symptomatic relief STV predicted the clinical outcome in 34 patients (81%) and CT predicted the outcome in 21 (50%) patients. Conclusion: There was a difference in biodistribution between 111In-pentetreotide and 90Y-lanreotide/ 90Y-SMT, especially in the kidneys, which may explain why there is minimal renal toxicity reported with 90Y-lanreotide/ 90Y-SMT therapies. Finally, the assessment of functional STV is more useful in monitoring the tumour response after treatment than CT. The changes in functional volumes after therapy correlate well with clinical response

SPECT/CT imaging of the lumbar spine in chronic low back pain: a case report

Mechanical low back pain is a common indication for Nuclear Medicine imaging. Whole-body bone scan is a very sensitive but poorly specific study for the detection of metabolic bone abnormalities. The accurate localisation of metabolically active bone disease is often difficult in 2D imaging but single photon emission computed tomography/computed tomography (SPECT/CT) allows accurate diagnosis and anatomic localisation of osteoblastic and osteolytic lesions in 3D imaging. We present a clinical case of a patient referred for evaluation of chronic lower back pain with no history of trauma, spinal surgery, or cancer. Planar whole-body scan showed heterogeneous tracer uptake in the lumbar spine with intense localisation to the right lateral aspect of L3. Integrated SPECT/CT of the lumbar spine detected active bone metabolism in the right L3/L4 facet joint in the presence of minimal signs of degenerative osteoarthrosis on CT images, while a segment demonstrating more gross degenerative changes was more quiescent with only mild tracer uptake. The usefulness of integrated SPECT/CT for anatomical and functional assessment of back pain opens promising opportunities both for multi-disciplinary clinical assessment and treatment for manual therapists and for research into the effectiveness of manual therapies

Predictors of antiproliferative effect of lanreotide autogel in advanced gastroenteropancreatic neuroendocrine neoplasms

PURPOSE: The antiproliferative properties of lanreotide autogel (LAN) in gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) were demonstrated in the CLARINET study. However, there is limited literature regarding factors that affect progression-free survival (PFS) in patients with GEP NENs treated with LAN. METHODS: We identified a total of 191 treatment-naive patients with advanced GEP NENs and positive SSTR uptake on imaging (Octreoscan or 68Gallium DOTATATE Positron Emission Tomography [68GaPET]) who received first-line LAN monotherapy, albeit at various starting doses (60, 90 or 120 mg/month). A group of 102 patients who initiated treatment at the standard dose of 120 mg/month were included in the study and further evaluated by univariate and multivariate analyses to identify predictors of PFS. RESULTS: The location of tumour primary was in the small bowel in 63 (62%), pancreas in 31 (30%) and colon/rectum in 8 patients (8%). The tumours were well-differentiated, and the majority were grade 1 (52%), or 2 (38%). About 60% of cases had progressive disease at the time of treatment initiation. Most patients with available pretreatment nuclear medicine imaging (Octreoscan or 68Ga PET) had a Krenning score of 3 (44%) or 4 (50%). The median PFS for the entire cohort was 19 months (95% CI 12, 26 months). The univariate analysis demonstrated that grade 2 tumours, progressive disease at baseline and metastatic liver disease were associated with a significantly shorter PFS, while other evaluated variables did not affect PFS at a statistically significant level. However, at multivariate analysis only the tumour grade remained statistically significant. CONCLUSIONS: The current study showed that, of many evaluated variables, only the tumour grade was predictive of PFS duration and this should be considered during patient selection for treatment

Guiding principles on the education and practice of theranostics.

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. 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. 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. The guiding principles for theranostics training outlined in this paper have immediate relevance for the safe and effective practice of theranostics

Changes observed in radionuclide bone scans during and after teriparatide treatment for osteoporosis

# The Author(s) 2011. This article is published with open access at Springerlink.com Purpose Visual changes on radionuclide bone scans have been reported with teriparatide treatment. To assess this, serial studies were evaluated and quantified in ten postmenopausal women with osteoporosis treated with teriparatide (20 μg/day subcutaneous) who had 99m Tc-methylene diphosphonate (MDP) bone scans (baseline, 3 and 18 months, then after 6 months off therapy). Methods Women were injected with 600 MBq 99m Tc-MDP, and diagnostic bone scan images were assessed at 3.5 h. Additional whole-body scans (10 min, 1, 2, 3 and 4 h) were analysed for 99m Tc-MDP skeletal plasma clearance (Kbone). Regional Kbone differences were obtained for the whole skeleton and six regions (calvarium, mandible, spine, pelvis, upper and lower extremities). Bone turnover markers (BTM) were also measured. Results Most subjects showed visual changes on 3- and 18month bone scan images that disappeared after 6 months off therapy. Enhanced uptake was seen predominantly in the calvarium and lower extremities. Whole skeleton Kbone displayed a median increase of 22 % (3 months, p=0.004) and 34 % (18 months, p=0.002) decreasing to 0.7% (6 months off therapy). Calvarium Kbone changes were three times larger than other sites. After 6 months off therapy, all Kbone and BTM values returned towards baseline

Stem cells from human extracted deciduous teeth expanded in foetal bovine and human sera express different paracrine factors after exposure to freshly prepared human serum

Background: The response of stem cells to paracrine factors within the host’s body plays an important role in the regeneration process after transplantation. The aim of this study was to determine the viability and paracrine factor profile of stem cells from human extracted deciduous teeth (SHED) pre-cultivated in media supplemented with either foetal bovine serum (FBS) or pooled human serum (pHS) in the presence of individual human sera (iHS). Methods: SHED (n=3) from passage 4 were expanded in FBS (FBS-SHED) or pHS (pHS-SHED) supplemented media until passage 7. During expansion, the proliferation of SHED was determined. Cells at passage 7 were further expanded in human serum from four individual donors (iHS) for 120 hours followed by assessment of cell viability and profiling of the secreted paracrine factors. Results: Proliferation of SHED was significantly higher (p<0.05) in pHS supplemented media compared to FBS supplemented media. pHS-SHED also maintained their higher proliferation rate compared to FBS-SHED in the presence of iHS. In iHS supplemented media, FBS-SHED expressed significantly higher levels of SDF-1A (p<0.05) after 24 hours compared to pHS-SHED. Similar results were found for HGF (p<0.01), LIF (p<0.05), PDGF-BB (p<0.05), SDF-1A (p<0.01), and IL-10 (p<0.05) when cell culture supernatants from FBS-SHED was profiled 120 hours post-incubation. Conclusion: SHED expanded in pHS instead of FBS have higher proliferative capacity and show an altered secretion profile. Further studies are needed to determine whether these differences could result in better engraftment and regeneration following transplantation

Patterns, Variants, Artifacts, and Pitfalls in Conventional Radionuclide Bone Imaging and SPECT/CT

Bone scintigraphy is one of the most common investigations performed in nuclear medicine and is used routinely in the evaluation of patients with cancer for suspected bone metastases and in various benign musculoskeletal conditions. Innovations in equipment design and other advances, such as single-photon emission computed tomography (SPECT), positron emission tomography, positron emission tomography/computed tomography (CT), and SPECT/CT have been incorporated into the investigation of various musculoskeletal diseases. Bone scans frequently show high sensitivity but specificity, which is variable or limited. Some of the limited specificity can be partially addressed by a thorough knowledge and experience of normal variants and common patterns to avoid misinterpretation. In this review, we discuss the common patterns, variants, artifacts, and pitfalls in conventional radionuclide planar, SPECT, and hybrid bone (SPECT/CT) imaging. Semin Nucl Med 39:380-395 (C) 2009 Elsevier Inc. All rights reserved