The radiological response of patients with advanced bone metastases to lutetium-177-labeled DOTA-ibandronic acid assessed by metabolic tumor volume

Abstract

Purpose: Effective management of patients undergoing treatment with lutetium-177 labeled DOTA-ibandronic acid (¹⁷⁷Lu-DOTA-IBA) necessitates the identification of radiological response biomarkers that can mitigate disease progression and facilitate patient stratification for subsequent treatment decisions. This study aims to evaluate the metabolic tumor volume (MTV) as a quantitative measure of radiological response in bone metastases using gallium-68 labeled DOTA-ibandronic acid (⁶⁸Ga-DOTA-IBA) PET/CT.

Methods: In a single-center retrospective study, ⁶⁸Ga-DOTA-IBA PET/CT scans of patients with bone metastases who received ¹⁷⁷Lu-DOTA-IBA injections. Eligible patients had available PET/CT scans both prior to ¹⁷⁷Lu-DOTA-IBA therapy and at treatment cessation. The Hermes system was employed to delineate regions of interest at baseline and at treatment cessation to measure the MTV of bone metastases. Spearman's rank correlation coefficient was utilized to assess the correlation between MTV and the baseline covariate, alkaline phosphatase (ALP). The Cox proportional hazards model and Kaplan-Meier curves were used to evaluate the association between baseline covariates, their changes at treatment termination, and overall survival (OS). The C-index measured the predictive discrimination of covariates for OS.

Results: Baseline ⁶⁸Ga-DOTA-IBA PET/CT images were available for 54 patients. Additionally, 30 patients underwent both baseline and post-treatment ⁶⁸Ga-DOTA-IBA PET/CT scans. Baseline MTV demonstrated a moderate correlation with ALP. Among baseline covariates, MTV and ALP were significantly associated with OS. Following treatment discontinuation, MTV decreased in 57% of patients, while ALP decreased in 83%. As a continuous variable, the relative change in MTV after treatment compared to baseline was significantly associated with OS, with a C-index of 0.69. Patients exhibiting a decrease in both MTV and ALP had a significantly longer median OS compared to those with a decrease in ALP alone.

Conclusions: Both baseline MTV and its changes at treatment cessation were significant parameters associated with OS. The study warrants prospective validation of MTV as a quantitative imaging response biomarker for predicting OS in patients with BM treated with ¹⁷⁷Lu-DOTA-IBA.

Keywords: 177Lu-DOTA-ibandronic acid; Bone metastases; Imaging biomarker; Metabolic tumor volume.

Fig. 1

Flow chart illustrating the evaluable patients

Fig. 2

⁶⁸Ga-DOTA-IBA PET MIP images of a 54-year-old man with lung cancer accompanied multiple metastases (including lymph node and bone metastases). MTV value decreased after Three treatment with ¹⁷⁷Lu-DOTA-IBA. Utilize the Hermes system to delineate hotspots (shown as red) for MTV calculations

Fig. 3

The Waterfall plot of the ALP (red) and MTV (green) change in each patients by number of ¹⁷⁷Lu-DOTA-IBA injections

Fig. 4

Kaplan Meier demonstrating the median overall survival of patients with ¹⁷⁷Lu-DOTA-IBA treatment induced decline in levels of ALP (n = 10) in comparison to patients with both treatment induced decline in both MTV and ALP levels (n = 15)