Changes in biodistribution on 68Ga-DOTA-Octreotate PET/CT after long acting somatostatin analogue therapy in neuroendocrine tumour patients may result in pseudoprogression

Martin H Cherk,Rodney J Hicks,Michael S Hofman,Grace Kong

doi:10.1186/s40644-018-0136-x

Abstract

BackgroundTo evaluate the effects of long-acting somatostatin analogue (SSA) therapy on 68Ga-DOTA-octreotate (GaTate) uptake at physiological and metastatic sites in neuroendocrine tumour (NET) patients.MethodsTwenty-one patients who underwent GaTate PET/CT before and after commencement of SSA therapy were reviewed. Maximum standardized uptake values (SUVmax) were measured in normal organs. Changes in uptake of 49 metastatic lesions in 12 patients with stable disease were also compared. Serum chromogranin-A (CgA) levels were available for correlation between scans in 17/21 patients.ResultsMean thyroid, spleen and liver SUVmax decreased significantly following SSA therapy from a baseline of 5.9 to 3.5, 30.3 to 23.1 and 10.3 to 8.0, respectively (p = < 0.0001 for all). Pituitary SUVmax increased from 10.2 to 11.0 (p = 0.004) whereas adrenal and salivary gland SUVmax did not change. Tumour SUVmax increased in 7 of 12 patients with stable disease; CgA was stable or decreasing in 5 of these patients. 30/49 (61%) metastatic lesions had an increase in SUVmax and lesion-to-liver uptake ratio increased in 40/49 (82%) following SSA therapy.ConclusionLong-acting SSA therapy decreases GaTate uptake in the thyroid, spleen and liver but in most cases increases intensity of uptake within metastases. This has significant implications for interpretation of GaTate PET/CT following commencement of therapy as increased intensity alone may not represent true progression. Our findings also suggest pre-dosing with SSA prior to PRRT may enable higher doses to be delivered to tumour whilst decreasing dose to normal tissues.

Highlights

To evaluate the effects of long-acting somatostatin analogue (SSA) therapy on 68Ga-DOTA-octreotate (GaTate) uptake at physiological and metastatic sites in neuroendocrine tumour (NET) patients
Changes in metastatic lesion uptake SUVmax of 49 metastatic lesions in patients with stable disease (n = 12) were measured at baseline and following long acting somatostatin analogue therapy (1–5 lesions measured per patient) (Table 2). 30/49 (61%) of metastatic lesions had an increase in SUVmax following somatostatin analogues (SSA) therapy
Our findings demonstrate that long-acting SSA therapy has variable effects on physiological 68Ga-DOTAOctreotate uptake in different organs with reduction of uptake in the thyroid gland, spleen and liver, slight increase in uptake in the pituitary gland and no effect on salivary and adrenal gland uptake

Summary

Introduction

To evaluate the effects of long-acting somatostatin analogue (SSA) therapy on 68Ga-DOTA-octreotate (GaTate) uptake at physiological and metastatic sites in neuroendocrine tumour (NET) patients. The high prevalence of SSTR overexpression in NETs has enabled the use of synthetic somatostatin analogues (SSA) to control symptoms related to over production of biologically active amines and peptide hormones frequently associated with NETs and to possibly delay disease progression [5,6,7,8]. These are generally administered as slow-release formulations to increase patient convenience. PRRT using 177Lu-DOTA-octreotate or 90Y–DOTA-octreotate have significant efficacy in controlling NETs that have progressed despite SSA therapy and is considered when GaTate PET uptake at tumour sites is greater than background liver uptake, indicating a sufficient target [10,11,12,13,14]

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