EANM dosimetry committee recommendations for dosimetry of 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands

Abstract

The purpose of the EANM Dosimetry Committee is to provide recommendations and guidance to scientists and clinicians on patient-specific dosimetry. Radiopharmaceuticals labelled with lutetium-177 (177Lu) are increasingly used for therapeutic applications, in particular for the treatment of metastatic neuroendocrine tumours using ligands for somatostatin receptors and prostate adenocarcinoma with small-molecule PSMA-targeting ligands. This paper provides an overview of reported dosimetry data for these therapies and summarises current knowledge about radiation-induced side effects on normal tissues and dose-effect relationships for tumours. Dosimetry methods and data are summarised for kidneys, bone marrow, salivary glands, lacrimal glands, pituitary glands, tumours, and the skin in case of radiopharmaceutical extravasation. Where applicable, taking into account the present status of the field and recent evidence in the literature, guidance is provided. The purpose of these recommendations is to encourage the practice of patient-specific dosimetry in therapy with 177Lu-labelled compounds. The proposed methods should be within the scope of centres offering therapy with 177Lu-labelled ligands for somatostatin receptors or small-molecule PSMA.

Keywords: Dosimetry; Lutetium-177; Neuroendocrine; PSMA-targeting ligands; Prostate adenocarcinoma; Somatostatin-receptor ligands.

Fig. 1

Self-absorbed energy per unit of TIA for 177Lu as a function of mass, based on $S$-values for unit density spheres for IDAC-Dose 2.1, Olinda v.1, v.2.1, and v.2.2. The result of LED from recent radionuclide data is also shown (dashed horizontal line) [1]. The blue band indicates an offset of ±2% from the values for IDAC-Dose 2.1

Fig. 2

Quantification of the TIA from a hypothetical TAC. The red line describes the true, underlying activity retention. Black dots indicate activity measurements performed at nominal times of 5, 24, 48, 72, and 168 h. Red dots indicate measurements that were omitted from this nominal scheme. Panels A–I illustrate different sampling and fitting scenarios and also include the estimated TIA as a percentage of the reference TIA. A–C trapezoidal integration based on 5 (A), or 3 data points (B, C) where C includes extrapolation beyond last data point; D–F integration based on mono-exponential curve fitting to 3 data points at different times; G–I integration based on bi-exponential curve fitting to 4–5 data points

Fig. 3

A Histogram of effective decay constants for a patient population with a mean of 0.013 h−1 and coefficient of variation of 27%. B–D Solid lines show TACs estimated from an activity measurement at 96 h (B), 24 h (C), and 196 h (D) combined with the mean population half-life. Dotted lines indicate the standard uncertainty in the respective TAC, yielding relative uncertainties in the TIA that are up to 10% for 96 h (B), 26% for 24 h (C), and 60% for 192 h (D)

Fig. 4

Anterior maximum-intensity projection of pre-therapy [68Ga]Ga-PSMA PET/CT (left) and [177Lu]Lu-PSMA-therapy gamma camera image (right) in a patient treated for metastatic prostate cancer. Large uptake can be observed in the different salivary glands and in lacrimal glands

Fig. 5

[68Ga]Ga-DOTA-TATE PET/CT of the head-and-neck region of a NET patient. Arrows indicate the radiopharmaceutical uptake in the pituitary region