Arterial effects of anthracycline: structural and inflammatory assessments in non-human primates and lymphoma patients using 18F-FDG positron emission tomography.

Background: Anthracyclines, such as doxorubicin, are important anti-cancer therapies but are associated with arterial injury. Histopathological insights have been limited to small animal models and the role of inflammation in the arterial toxic effects of anthracycline is unclear in humans. Our aims were: 1) To evaluate aortic media fibrosis and injury in non-human primates treated with anthracyclines; 2) To assess the effect of anthracycline on aortic inflammation in patients treated for lymphoma. Methods: 1) African Green monkeys (AGM) received doxorubicin (30-60 mg/m2/biweekly IV, cumulative dose: 240 mg/m2). Blinded histopathologic analyses of collagen deposition and cell vacuolization in the ascending aorta were performed 15 weeks after the last doxorubicin dose and compared to 5 age- and gender-matched healthy, untreated AGMs. 2) Analysis of the thoracic aorta of patients with diffuse large B-cell lymphoma (DLBCL), at baseline and after doxorubicin exposure, was performed using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in this observational study. The primary outcome was change in maximal tissue-to-background ratio (TBRmax) of the thoracic aorta from baseline to their end-of-treatment clinical PET/CT. Results: In AGMs, doxorubicin exposure was associated with greater aortic fibrosis (collagen deposition: doxorubicin cohort 6.23±0.88% vs. controls 4.67±0.54%; p=0.01) and increased intracellular vacuolization (doxorubicin 66.3 ± 10.1 vs controls 11.5 ± 4.2 vacuoles/field, p<0.0001) than untreated controls.In 101 patients with DLBCL, there was no change in aortic TBRmax after anthracycline exposure (pre-doxorubicin TBRmax 1.46±0.16 vs post-doxorubicin TBRmax 1.44±0.14, p=0.14). The absence of change in TBRmax was consistent across all univariate analyses. Conclusions: In a large animal model, anthracycline exposure was associated with aortic fibrosis. In patients with lymphoma, anthracycline exposure was not associated with aortic inflammation.Further research is required to elucidate the mechanisms of anthracycline-related vascular harm.

Quantitative uptake in 99m Tc-EDDA/HYNIC-TOC somatostatin receptor imaging - the effect of long-acting release somatostatin analogue therapy.

PURPOSE: Withdrawal of long-acting release somatostatin analogue (LAR-SSA) treatment before somatostatin receptor imaging is based on empirical reasoning that it may block uptake at receptor sites. This study aims to quantify differences in uptake of 99m Tc-EDDA/HYNIC-TOC between patients receiving LAR-SSA and those who were not. METHODS: Quantification of 177 patients (55 on LAR-SSA) imaged with 99m Tc-EDDA/HYNIC-TOC was performed, with analysis of pathological tissue and organs with physiological uptake using thresholded volumes of interest. Standardised uptake values (SUVs) and tumour/background (T/B) ratios were calculated and compared between the two patient groups. RESULTS: SUVs were significantly lower for physiological organ uptake for patients on LAR-SSA (e.g. spleen: SUV max 13.3 ±â€…5.9 versus 33.9 ±â€…9.0, P  < 0.001); there was no significant difference for sites of pathological uptake (e.g. nodal metastases: SUV max 19.2 ±â€…13.0 versus 17.4 ±â€…11.5, P  = 0.552) apart from bone metastases (SUV max 14.1 ±â€…13.5 versus 7.7 ±â€…8.0, P  = 0.017) where it was significantly higher. CONCLUSION: LAR-SSA has an effect only on physiological organ uptake of 99m Tc-EDDA/HYNIC-TOC, reducing uptake. It has no significant effect on pathological uptake for most sites of primary and metastatic disease. This should be taken into account if making quantitative measurements, calculating T/B ratios or assigning Krenning Scores. There is the potential for improved dosimetric results in Peptide Receptor Radionuclide Therapy by maintaining patients on LAR-SSA.

Characterisation of 99mTc EDDA/HYNIC-TOC (Tektrotyd) physiological and neuroendocrine tumour uptake using SPECT/CT standardised uptake values: initial experience.

99mTc Ethylene diamine N,N'-diacetic acid hydrazinonicotinamide-conjugated Tyr3-octreotide (99mTc EDDA/HYNIC-TOC) single photon emission tomography/computed tomography (SPECT/CT) imaging of somatostatin receptors is used in the assessment of neuroendocrine tumours (NETs). The objective of this study was to characterise quantitative standardised uptake value (SUV) SPECT/CT of normal physiological uptake and NET disease. Forty-four patients (22 female and 22 male) referred for 99mTc EDDA/HYNIC-TOC SPECT/CT imaging for diagnosis/primary staging (n = 28) or the assessment of residual/recurrent disease (n = 16) were included. SPECT/CT SUVmax values were determined for normal physiological uptake (spleen, kidney, liver and bone) and NET disease (liver metastases, metastatic lymph nodes, bone metastases and intrapulmonary lesions). Statistical testing was performed to compare normal uptake and NET disease uptake in liver and bone (Student's t-test). The highest normal physiological uptake was observed in the spleen (mean SUVmax 29.8, SD 13.7), with lower uptake in the kidneys (16.7, 3.2) and liver (7.3, 2.1). Increased SUVmax values were observed in primary tumour and metastatic disease, greatest in liver metastases (21.8, 13.3), with lower, similar values obtained for metastatic lymph nodes (16.3, 7.5) and intrapulmonary lesions (17.5, 16.8). SUVmax in bone metastases averaged 12.9 (7.0). Significant differences were observed between normal and metastatic SUVmax in the liver and bone (P < 0.01). SPECT/CT SUV quantification is feasible in a manner similar to PET/CT. 99mTc EDDA/HYNIC-TOC SPECT/CT SUVmax has been characterised in NET disease, demonstrating high target to non-target ratios for primary tumours and metastatic lesions.

Optimization of the CT component of SPECT-CT and establishment of local CT diagnostic reference levels for clinical practice.

OBJECTIVE: The aim of this study was to perform a process of optimization and establish local diagnostic reference levels (DRLs) for the computed tomography (CT) component of single-photon emission computed tomography (SPECT)-CT imaging, for use in clinical practice. METHODS: A multidisciplinary group defined categories for the clinical purpose of the CT component of local SPECT-CT examinations. Each of the examinations were assigned a category, and optimization of acquisition and reconstruction parameters was performed to achieve the required image quality. Dose data were collated for 754 SPECT-CT scans performed on three systems over 10 months. The third quartile values for volume CT dose index and dose length product were calculated and established as local DRLs. RESULTS: Four categories of CT examinations were defined: attenuation correction; localization and attenuation correction; localization, characterization and attenuation correction; and diagnostic and attenuation correction. Local DRLs were established for 11 examinations. Reference was made to the proposed national DRLs set by a recent UK survey. CONCLUSION: This work describes a process of optimization and the creation of practical and effective local DRLs. These can be used in local audit of practice. In future, improved descriptors and standardization of SPECT-CT use would allow more practicable UK national DRLs to be created.