Single-centre experience with peptide receptor radionuclide therapy for neuroendocrine tumours (NETs): results using a theranostic molecular imaging-guided approach.

AIM: To summarise our centre's experience managing patients with neuroendocrine tumours (NETs) in the first 5 years after the introduction of peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-octreotate (LUTATE). The report emphasises aspects of the patient management related to functional imaging and use of radionuclide therapy. METHODS: We describe the criteria for treatment with LUTATE at our centre, the methodology for patient selection, and the results of an audit of clinical measures, imaging results and patient-reported outcomes. Subjects are treated initially with four cycles of ~ 8 GBq of LUTATE administered as an outpatient every 8 weeks. RESULTS: In the first 5 years offering LUTATE, we treated 143 individuals with a variety of NETs of which approx. 70% were gastroentero-pancreatic in origin (small bowel: 42%, pancreas: 28%). Males and females were equally represented. Mean age at first treatment with LUTATE was 61 ± 13 years with range 28-87 years. The radiation dose to the organs considered most at risk, the kidneys, averaged 10.6 ± 4.0 Gy in total. Median overall survival (OS) from first receiving LUTATE was 72.5 months with a median progression-free survival (PFS) of 32.3 months. No evidence of renal toxicity was seen. The major long-term complication seen was myelodysplastic syndrome (MDS) with a 5% incidence. CONCLUSIONS: LUTATE treatment for NETs is a safe and effective treatment. Our approach relies heavily on functional and morphological imaging informing the multidisciplinary team of NET specialists to guide appropriate therapy, which we suggest has contributed to the favourable outcomes seen.

Partial volume effect in SPECT & PET imaging and impact on radionuclide dosimetry estimates.

Objectives: The spatial resolution of emission tomographic imaging systems can lead to a significant underestimation in the apparent radioactivity concentration in objects of size comparable to the resolution volume of the system. The aim of this study was to investigate the impact of the partial volume effect (PVE) on clinical imaging in PET and SPECT with current state-of-the-art instrumentation and the implications that this has for radionuclide dosimetry estimates. Methods: Using the IEC Image Quality Phantom we have measured the underestimation in observed uptake in objects of various sizes for both PET and SPECT imaging conditions. Both single pixel measures (i.e., SUVmax) and region of interest mean values were examined over a range of object sizes. We have further examined the impact of the PVE on dosimetry estimates in OLINDA in 177Lu SPECT imaging based on a subject with multiple somatostatin receptor positive paragangliomas in the head and neck. Results: In PET, single pixel estimates of uptake are affected for objects less than approximately 18 mm in minor axis with existing systems. In SPECT imaging with medium energy collimators (e.g., for 177Lu imaging), however, the underestimates are far greater, where single pixel estimates in objects less than 2-3×the resolution volume are significantly impacted. In SPECT, region of interest mean values are underestimated in objects less than 10 cm in diameter. In the clinical case example, the dosimetry measured with SPECT ranged from more than 60% underestimate in the largest lesion (28×22 mm in maximal cross-section; 10.2 cc volume) to >99% underestimate in the smallest lesion (4×5 mm; 0.06 cc). Conclusion: The partial volume effect remains a significant factor when estimating radionuclide uptake in vivo, especially in small volumes. Accurate estimates of absorbed dose from radionuclide therapy will be particularly challenging until robust solutions to correct for the PVE are found.

Theranostic SPECT reconstruction for improved resolution: application to radionuclide therapy dosimetry.

BACKGROUND: SPECT-derived dose estimates in tissues of diameter less than 3× system resolution are subject to significant losses due to the limited spatial resolution of the gamma camera. Incorporating resolution modelling (RM) into the SPECT reconstruction has been proposed as a possible solution; however, the images produced are prone to noise amplification and Gibbs artefacts. We propose a novel approach to SPECT reconstruction in a theranostic setting, which we term SPECTRE (single photon emission computed theranostic reconstruction); using a diagnostic PET image, with its superior resolution, to guide the SPECT reconstruction of the therapeutic equivalent. This report demonstrates a proof in principle of this approach. METHODS: We have employed the hybrid kernelised expectation maximisation (HKEM) algorithm implemented in STIR, with the aim of producing SPECT images with PET-equivalent resolution. We demonstrate its application in both a dual 68Ga/177Lu IEC phantom study and a clinical example using 64Cu/67Cu. RESULTS: SPECTRE is shown to produce images comparable in accuracy and recovery to PET with minimal introduction of artefacts and amplification of noise. CONCLUSION: The SPECTRE approach to image reconstruction shows improved quantitative accuracy with a reduction in noise amplification. SPECTRE shows great promise as a method of improving SPECT radioactivity concentrations, directly leading to more accurate dosimetry estimates in small structures and target lesions. Further investigation and optimisation of the algorithm parameters is needed before this reconstruction method can be utilised in a clinical setting.

Diagnostic performance of whole-body SPECT/CT in bone metastasis detection using 99mTc-labelled diphosphate: a systematic review and meta-analysis.

AIM: To evaluate the diagnostic performance of whole-body (WB) integrated single photon emission tomography (SPECT)/computed tomography (CT) in detecting bone metastasis (BM) and to investigate whether WB-SPECT/CT offered any additional benefit value compared to planar bone scintigraphy (PBS) with 99mTc-hydroxy-methylene diphosphonate or 99mTc methylene diphosphonate. MATERIALS AND METHODS: Medline, EMBASE, SCOPUS, Web of Science, and CINAHL were searched systematically up to 28 August 2019. All studies using histopathological analysis and/or follow-up imaging and clinical data as the reference standard were eligible for inclusion. RESULTS: Eleven studies (1,611 patients) were analysed. Based on patient analysis, the sensitivity, specificity, and area under the curve (AUC) of WB-SPECT/CT were 92% (92% confidence interval [CI], 89-95%), 95% (95% CI, 94-96%), and 0.9835, respectively, in the case of negative equivocal findings for BM, and 94% (95% CI, 91-96%), 94% (95% CI, 92-95%), and 0.9790, respectively, when regarded positive. On a lesion basis, these parameters were 91% (95% CI, 89-94%), 96% (95% CI, 94-97%), and 0.9906, respectively, in the case negative equivocal findings, and 92% (95% CI, 89-94%), 95% (95% CI, 94-97%), and 0.9898, respectively, when regarded positive. Comparing 1,265 patients from eight studies, higher sensitivity (92% versus 74%, p=0.04) and specificity for WB-SPECT/CT against PBS (93% versus 80%, p=0.01) in the case of positive equivocal findings; however, when regarded negative, WB-SPECT/CT demonstrated higher sensitivity (91% versus 70%, p=0.01), but no significant difference was apparent in specificity (94% versus 89%, p=0.07). CONCLUSION: Compared to PBS, WB-SPECT/CT had superior diagnostic accuracy in BM detection and exhibited a more reliable performance with less equivocal results.