The impact of circadian rhythms on medical imaging and radiotherapy regimes for the paediatric patient

Daily rhythmic changes are found in cellular events in cell cycle, DNA repair, apoptosis and angiogenesis in both normal and tumour tissue, as well as in enzymatic activity and drug metabolism. In this paper, we hypothesize that circadian rhythms need to be considered in radiation protection and optimization in personalized medicine, especially for paediatric care. The sensitivity of the eye lens to ionizing radiation makes the case for limiting damage to the lens epithelium by planning medical radio-imaging procedures for the afternoon, rather than the morning. Equally, the tumour and normal tissue response to radiotherapy is also subject to diurnal variation enabling optimization of time of treatment

Successful receptor-mediated radiation therapy of xenografted human midgut carcinoid tumour

Somatostatin receptor (sstr)-mediated radiation therapy is a new therapeutic modality for neuroendocrine (NE) tumours. High expression of sstr in NE tumours leads to tumour-specific uptake of radiolabelled somatostatin analogues and high absorbed doses. In this study, we present the first optimised radiation therapy via sstr using [177Lu-DOTA0-Tyr3]-octreotate given to nude mice xenografted with the human midgut carcinoid GOT1. The tumours in 22 out of 23 animals given therapeutic amounts showed dose-dependent, rapid complete remission. The diagnostic amount (0.5 MBq [177Lu-DOTA0-Tyr3]-octreotate) did not influence tumour growth and was rapidly excreted. In contrast, the therapeutic amount (30 MBq [177Lu-DOTA0-Tyr3]-octreotate) induced rapid tumour regression and entrapment of 177Lu so that the activity concentration of 177Lu remained high, 7 and 13 days after injection. The entrapment phenomenon increased the absorbed dose to tumours from 1.6 to 4.0 Gy MBq−1 and the tumours in animals treated with 30 MBq received 120 Gy. Therapeutic amounts of [177Lu-DOTA0-Tyr3]-octreotate rapidly induced apoptosis and gradual development of fibrosis in grafted tumours. In conclusion, human midgut carcinoid xenografts can be cured by receptor-mediated radiation therapy by optimising the uptake of radioligand and taking advantage of the favourable change in biokinetics induced by entrapment of radionuclide in the tumours

Advances in the diagnostic imaging of pheochromocytomas

Eva Forssell-Aronsson1, Emil Schüler1, Håkan Ahlman21Department of Radiation Physics, 2Department of Surgery, Lundberg Laboratory of Cancer Research, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, SwedenAbstract: Pheochromocytomas (PCs) and paragangliomas (PGLs) are routinely localized by computed tomography (CT), magnetic resonance imaging (MRI), and metaiodobenzylguanidine (MIBG) scintigraphy. CT can identify tumors with high sensitivity but rather low specificity. MRI has higher sensitivity and specificity than CT and is superior to detect extra-adrenal disease. Radioiodinated MIBG scintigraphy has been used for more than 30 years and is based on MIBG uptake via the norepinephrine transporter on the cell membrane. The technique is very useful for whole-body studies in case of multiple primary tumors or metastases. Tumors with sole production of dopamine usually cannot be visualized with MIBG and may require positron emission tomographic (PET) studies with 18F-labeled radiotracers. Somatostatin receptor scintigraphy (SRS) using the radiolabeled somatostatin analog octreotide (based on the expression of the somatostatin receptors 2 and 5 by the tumor) can demonstrate PGL or metastases not visualized by MIBG. In this article, we review the use of MIBG scintigraphy to diagnose PC/PGL and compare the sensitivity and specificity with that of CT and MRI. We also describe the recent SRS and PET techniques and review the latest results of clinical studies by comparing these imaging modalities. Future perspectives of functional imaging modalities for PC/PGL are finally presented.Keywords: MIBG, scintigraphy, pheochromocytoma, paraganglioma, PE