Nuclear medicine imaging for bone metastases assessment: what else besides bone scintigraphy in the era of personalized medicine?

Abstract

Accurate detection and reliable assessment of therapeutic responses in bone metastases are imperative for guiding treatment decisions, preserving quality of life, and ultimately enhancing overall survival. Nuclear imaging has historically played a pivotal role in this realm, offering a diverse range of radiotracers and imaging modalities. While the conventional bone scan using ^99mTc marked bisphosphonates has remained widely utilized, its diagnostic performance is hindered by certain limitations. Positron emission tomography, particularly when coupled with computed tomography, provides improved spatial resolution and diagnostic performance with various pathology-specific radiotracers. This review aims to evaluate the performance of different nuclear imaging modalities in clinical practice for detecting and monitoring the therapeutic responses in bone metastases of diverse origins, addressing their limitations and implications for image interpretation.

Keywords: 18 F-FDG; 18 F-fluorocholine; 18F-DOPA; 18F-NaF?; 68Ga-DOTA; 99mTc; bone metastases; bone scan.

Figure 1

^99mTc-HMDP SPECT/CT in a first patient with a bone metastatic prostate adenocarcinoma under first generation hormonotherapy for 2 years, showing a right posterior iliac sclerotic bone metastasis with a high uptake (A,B). Routine follow-up 6 months later showed shading of the iliac metastasis and less intense uptake (E,F), linked to a progression confirmed by a rising PSA and subsequent imaging. ^99mTc-HMDP SPECT/CT in a second patient with a bone metastatic breast invasive lobular carcinoma, displaying a vertebral sclerotic metastasis with a high uptake at initial staging (C,D). Routine follow-up 12 months later showed a shadowing of the metastasis and a less intense uptake (G,H), indicative of a therapeutic response confirmed by clinical evolution and subsequent imaging.

Figure 2

¹⁸F-FDG PET/CT (A,B) and ^99mTc-HMDP SPECT/CT (C,D) in a 75 years-old woman referred for initial staging of an invasive lobular carcinoma of the breast, showing multiples subcentimetric sclerotic bone lesions, linked to a diffuse bone invasion on the rest of the scans (not shown), without ¹⁸F-FDG and ^99mTc-HMDP uptake, corresponding to bone metastases confirmed by biopsy.

Figure 3

⁶⁸Ga-PSMA PET/CT [anterior MIP (A), sagittal PET/CT (B)] and ¹⁸F-Fluorocholine PET/CT [anterior MIP (C), sagittal PET/CT (D)] illustrating the difference in sensitivity between the two radiotracers, ⁶⁸Ga-PSMA PET/CT showing more bone metastases than ¹⁸F-Fluorocholine scan.

Figure 4

¹⁸F-FDG (A) and ⁶⁸Ga-DOTATOC (B–D) PET/CT results (anterior MIP, coronal PET/CT, coronal CT) in a 48 years-old woman with grade 2 metastatic pancreatic neuroendocrine tumor showing multiple bone sclerotic metastases characterized by intense and pathologic ⁶⁸Ga-DOTATOC uptake. ¹⁸F-FDG PET/CT failed to detect metastatic spread.

Figure 5

Typical example of “flip-flop” effect (anterior PET MIP, sagittal PET/CT) in a patient with metastatic low-grade (G1) small bowel NET. 18F-FDOPA PET showed multiple sclerotic bone metastases (A,B) not detectable by 18F-FDG PET (C,D), emphasizing the role of tumor grade in the selection of the optimal diagnostic radiotracer.