Quantifying the effects of absorbed dose from radioembolisation on healthy liver function with [99mTc]TcMebrofenin.

PURPOSE: To quantify the effects of absorbed radiation dose on healthy liver parenchyma following radioembolisation (RE) using [99mTc]TcMebrofenin to analyse both global and regional liver function. METHODS: Patients having RE to treat hepatic disease underwent a [99mTc]TcMebrofenin hepatobilliary scintigraphy (HBS) study at both baseline and 8 weeks following treatment. Changes in global liver uptake rate were compared with healthy liver absorbed dose measures derived from the post-treatment 90Y PET/CT, including average dose, minimum dose to 70% of the volume (D70) and volume receiving at least 50 Gy (V50). Changes in functional burden associated with treatment and spared liver volumes in patients receiving lobar RE were also assessed, as were changes experienced by regional volumes corresponding to various dose ranges. Standard liver function pathology tests (LFTs) (bilirubin, albumin, ALP, AST, ALT and GGT) were examined for changes between baseline and post-treatment. RESULTS: Thirty-five patients were included in the study, of which, 9 had lobar treatment. A significant linear correlation was found between both baseline global liver uptake rate (negative) and D70 with change in global liver uptake rate. Patients undergoing lobar treatments demonstrated a shift in functional burden, and a significant difference was seen between the mean dose corresponding to liver volumes that increased their functional burden (9 Gy) and those that decreased their functional burden (35 Gy). No baseline LFTs predicted a decrease in global liver function; however, D70 demonstrated a linear correlation with changes in bilirubin and GGT. CONCLUSIONS: Given the significant negative relationship between baseline and change in global liver uptake rate, baseline HBS studies should not be used alone to disqualify patients considered for RE. In terms of treatment planning and evaluation, D70 may be the most appropriate metric of dose, with values greater than 15 Gy indicative of a likely drop in global liver function. The evidence of increasing functional burden in spared liver volumes suggests that patients at risk of complications could benefit from a lobar approach to treatment.

Dual Somatostatin Receptor/FDG PET/CT Imaging in Metastatic Neuroendocrine Tumours: Proposal for a Novel Grading Scheme with Prognostic Significance.

Background: PET scans using FDG and somatostatin receptor imaging agents have both been used to study neuroendocrine tumours. Most reports have documented the sensitivity and specificity of each radiopharmaceutical independently, and even suggested the superiority of one over the other for different grades of disease. Aim: The aim of this work was to develop a grading scheme that describes the joint results of both the FDG and somatostatin receptor imaging PET scans in staging subjects with neuroendocrine tumours in a single combined parameter. The grading scheme that has been developed is referred to as the NETPET grade. Methods: This is a retrospective study which assessed subjects who had both FDG and somatostatin receptor PET imaging at our institution within 31 days of each other. The NETPET grade was assigned by experienced nuclear medicine physicians and compared with other clinical data such as WHO grade and overall survival. Results: In the period 2011-2015 we were able to recruit 62 subjects with histologically proven metastatic neuroendocrine tumour for review. The NETPET grade incorporating both the FDG and somatostatin receptor imaging results was significantly correlated with overall survival by univariate analysis (p=0.0018), whereas in this cohort the WHO grade at the time of diagnosis did not correlate with survival. Conclusions: The NETPET grade has promise as a prognostic imaging biomarker in neuroendocrine tumours. It permits the capturing of the complexity of dual radiotracer imaging in a single parameter which describes the subjects' disease and is readily amenable to use in patient management and further research.

In Vivo Measurement and Characterization of a Novel Formulation of [177Lu]-DOTA-Octreotate.

OBJECTIVES: Lutetium-177 can be made with high specific activity and with no other isotopes of lutetium present, referred to as "No Carrier Added" (NCA) 177Lu. We have radiolabelled DOTA-conjugated peptide DOTA-(Tyr3)-octreotate with NCA 177Lu ("NCA-LuTATE") and used it in nearly 40 therapeutic administrations for subjects with neuroendocrine tumours or meningiomas. In this paper, we report on our initial studies on aspects of the biodistribution and dosimetry of NCA-LuTATE from gamma camera 2D whole body (WB) and quantitative 3D SPECT (qSPECT) 177Lu imaging. METHODS: Thirteen patients received 39 NCA-LuTATE injections. Extensive WB planar and qSPECT imaging was acquired at approximately 0.5, 4, 24 and 96 h to permit estimates of clearance and radiation dose estimation using MIRD-based methodology (OLINDA-EXM). RESULTS: The average amount of NCA-Lutate administered per cycle was 7839±520 MBq. Bi-exponential modelling of whole body clearance showed half lives for the fast & slow components of t½=2.1±0.6 h and t½=58.1±6.6 h respectively. The average effective dose to kidneys was 3.1±1.0 Gy per cycle. In eight patients completing all treatment cycles the average total dose to kidneys was 11.7±3.6 Gy. CONCLUSIONS: We have shown that NCA-LuTATE has an acceptable radiation safety profile and is a suitable alternative to Carrier-Added 177Lu formulations. The fast component of the radiopharmaceutical clearance was closely correlated with baseline renal glomerular filtration rate, and this had an impact on radiation dose to the kidneys. In addition, it has less radioactive waste issues and requires less peptide per treatment.