^99mTc-Demotate 1: first data in tumour patients—results of a pilot/phase I study

Somatostatin receptor (SSTR) scintigraphy with indium-111 DTPA-octreotide has become a routine diagnostic procedure in oncology. However, it suffers some drawbacks concerning the limited availability, suboptimal imaging properties and elevated radiation burden of ¹¹¹In. We have recently been involved in the development of a new tetraamine-functionalised [Tyr³]octreotate derivative (Demotate 1) that can be easily labelled with technetium-99m at high specific activities. ^99mTc-Demotate 1 showed promising properties in preclinical studies. In this study we report on the first experience with ^99mTc-Demotate 1 in patients. Six patients (mean age 56 years) with carcinoid tumours (n=2) or endocrine pancreatic tumours (n=4) with previously positive SSTR scintigraphy were enrolled in the study. Patients were injected with 500–600 MBq ^99mTc-Demotate 1. Clinical and laboratory parameters were controlled up to 3 months p.i. Blood samples were taken at various time points up to 24 h p.i., and urine was collected up to 24 h. Whole-body images were acquired at 15–30 min, 1–2 h, 4 h and 24 h p.i. with additional single-photon emission tomography imaging at 1–4 h. Blood excretion was very rapid, with <2%ID in plasma after 1 h, and urinary excretion <20% ID after 6 h. Two patients complained of mild gastrointestinal problems and paraesthesia, but no other adverse reactions were observed. SSTR-positive tumours were rapidly visualised as early as 15 min p.i., with maximum tumour uptake (up to 19% ID) and tumour/organ ratios as early as 1 h p.i. Organs of predominant physiological uptake were the spleen and the kidneys, with no intestinal excretion detectable up to 24 h. ^99mTc-Demotate 1 detected 11 lesions while In-Oct detected ten; differences in uptake behaviour were observed in three patients. This study shows for the first time that peptides derivatised with a tetraamine ligand for labelling with ^99mTc show suitable properties for receptor imaging in patients. ^99mTc-Demotate 1 is a promising agent for the visualisation of SSTR-positive lesions in patients, allowing rapid imaging as early as 1 h p.i.; some differences are observed in pharmacokinetic behaviour compared with ¹¹¹In-DTPA-octreotide.