Immunomodulatory effects of targeted radionuclide therapy.

It is now clear that conventional radiation therapy can reinstate cell death immunogenicity. Recent preclinical data indicate that targeted radionuclide therapy that irradiate tumors at continuous low dose rate also can elicit immunostimulatory effects and represents a promising strategy to circumvent immune checkpoint inhibitor resistance. In this perspective, we discuss the accumulating preclinical and clinical data suggesting that activation of the immune system through the cGAS-STING axis and the release of extracellular vesicles by irradiated cells, participate to this antitumor immunity. This should need to be considered for adapting clinical practices to state of the art of the radiobiology and to increase targeted radionuclide therapy effectiveness.

Clinical implementation of PLANET® Dose for dosimetric assessment after [177Lu]Lu-DOTA-TATE: comparison with Dosimetry Toolkit® and OLINDA/EXM® V1.0.

BACKGROUND: The aim of this study was to compare a commercial dosimetry workstation (PLANET® Dose) and the dosimetry approach (GE Dosimetry Toolkit® and OLINDA/EXM® V1.0) currently used in our department for quantification of the absorbed dose (AD) to organs at risk after peptide receptor radionuclide therapy with [177Lu]Lu-DOTA-TATE. METHODS: An evaluation on phantom was performed to determine the SPECT calibration factor variations over time and to compare the Time Integrated Activity Coefficients (TIACs) obtained with the two approaches. Then, dosimetry was carried out with the two tools in 21 patients with neuroendocrine tumours after the first and second injection of 7.2 ± 0.2 GBq of [177Lu]Lu-DOTA-TATE (40 dosimetry analyses with each software). SPECT/CT images were acquired at 4 h, 24 h, 72 h and 192 h post-injection and were reconstructed using the Xeleris software (General Electric). The liver, spleen and kidneys masses and TIACs were determined using Dosimetry Toolkit® (DTK) and PLANET® Dose. The ADs were calculated using OLINDA/EXM® V1.0 and the Local Deposition Method (LDM) or Dose voxel-Kernel convolution (DK) on PLANET® Dose. RESULTS: With the phantom, the 3D calibration factors showed a slight variation (0.8% and 3.3%) over time, and TIACs of 225.19 h and 217.52 h were obtained with DTK and PLANET® Dose, respectively. In patients, the root mean square deviation value was 8.9% for the organ masses, 8.1% for the TIACs, and 9.1% and 7.8% for the ADs calculated with LDM and DK, respectively. The Lin's concordance correlation coefficient was 0.99 and the Bland-Altman plot analysis estimated that the AD value difference between methods ranged from - 0.75 to 0.49 Gy, from - 0.20 to 0.64 Gy, and from - 0.43 to 1.03 Gy for 95% of the 40 liver, kidneys and spleen dosimetry analyses. The dosimetry method had a minor influence on AD differences compared with the image registration and organ segmentation steps. CONCLUSIONS: The ADs to organs at risk obtained with the new workstation PLANET® Dose are concordant with those calculated with the currently used software and in agreement with the literature. These results validate the use of PLANET® Dose in clinical routine for patient dosimetry after targeted radiotherapy with [177Lu]Lu-DOTA-TATE.

[Bone quality evaluation in allograft hand transplant]. / Évaluation de la qualité de l'os dans les allogreffes de main.

Five bilateral forearms allograft have been performed between January 2000 and July 2009 in Lyon (France). The first four patients (three males, one female) have been the subject of an assessment of the bone quality of those allografts. The techniques selected for this study were: radioclinical analysis, bone scintigraphy, MRI, bone densitometry and High Resolution peripheral Quantitative Computed Tomography (HR-PQCT). Histology has been performed only on the first patient unilaterally grafted in 1998 who did not take part in this clinical research protocol, after amputation of his rejected graft. On the clinical, radiological and scintigraphical aspects, donor bone integration in hands allograft are good on a macroscopic point of view considering the healing and the general reaction of the bone in situation of fractures, infection and growth. The scintigraphy does not show important variations compared to the ones we can observe on contact with osteosynthesis material or during bone autografts. MRI found neither focal nor periosteal anomaly on grafted bone. The bone densitometry did not show significant difference with secondary osteoporosis one can observe in other grafted patients under immunosuppressive treatment. The HR-PQCT showed for the three males patients, a higher loss in volumetric density, for grafted bone than in the recipient patient control skeleton. Due to the few patients of this series, and the discrepancies in follow-up duration, the presented data have to be confirmed with further studies.