# Theranostics of Bone Metastases: The Role and Prospects of Bisphosphonate Radiopharmaceuticals

**Authors:** Yu Qian, Guangxing Yin, Yuhao Jiang, Peiwen Han, Junbo Zhang

PMC · DOI: 10.3390/ph19020295 · Pharmaceuticals · 2026-02-10

## TL;DR

This review explores how bisphosphonate-based radiopharmaceuticals can improve the diagnosis and treatment of bone metastases through personalized nuclear medicine.

## Contribution

The paper highlights the evolution and future directions of bisphosphonate-based theranostic agents for bone metastases.

## Key findings

- Bone-targeted radiopharmaceuticals are crucial for both diagnosing and treating bone metastases.
- Bisphosphonates serve as effective molecular scaffolds for developing next-generation theranostic agents.
- Theranostic strategies aim to enable individualized and precise dosimetry for improved patient outcomes.

## Abstract

Bone metastasis is among the most common complications of advanced malignant tumors and severely affects prognosis in patients. Nuclear medicine, particularly bone-targeted radiopharmaceuticals, plays a unique and pivotal role in the diagnosis and treatment of bone metastases. This review systematically outlines the evolutionary trajectory of bone-targeted radiopharmaceuticals. It revisits functional bone imaging agents based on Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET), as well as recently developed therapeutic radiopharmaceuticals for bone metastases. Building on this foundation, this article focuses on the advanced paradigm of “theranostics” in nuclear medicine, encompassing strategies for theranostic radionuclide pairing and the development of single-radionuclide theranostic agents, aiming to achieve individualized and precise dosimetry. Moreover, this review emphasizes bone-targeting molecular scaffolds, such as bisphosphonates, and highlights their potential and direction for optimization through rational drug design, with the goal of developing a new generation of highly effective and low-toxicity theranostic platforms. This work aims to provide systematic insights for enhancing the precise management of bone metastases.

## Full-text entities

- **Genes:** Irak1bp1 (interleukin-1 receptor-associated kinase 1 binding protein 1) [NCBI Gene 65099] {aka 4921528N06Rik, Aabp3, Aip70, Simpl}, H2ax (H2A.X variant histone) [NCBI Gene 15270] {aka H2A.X, H2afx, Hist5-2ax, gammaH2ax}, Tdrd7 (tudor domain containing 7) [NCBI Gene 85425] {aka Pctaire2bp}, Alb (albumin) [NCBI Gene 11657] {aka Alb-1, Alb1, BCL001, BCL002, BPL001}
- **Diseases:** breast cancer (MESH:D001943), renal toxicity (MESH:D007674), pathological fractures (MESH:D005598), vascular calcification (MESH:D061205), Bone Metastases (MESH:D009362), bone marrow toxicity (MESH:D001855), cytotoxicity (MESH:D064420), bone (MESH:D001847), spinal cord compression (MESH:D013117), osteolytic lesions (MESH:D030981), injury to (MESH:D014947), prostate cancer (MESH:D011471), PC-3 (MESH:D015324), bone pain (MESH:D010146), lung cancer (MESH:D008175), skeletal disorders (MESH:C564967), Cancer (MESH:D009369)
- **Chemicals:** 186Re (MESH:C000615079), beta-alanine (MESH:D015091), HYNIC (MESH:C117288), uranium (MESH:D014501), 99mTc-MAG3-HBP (MESH:C517543), Alendronate (MESH:D019386), HBED-CC (MESH:C075313), iodine (MESH:D007455), Ga (MESH:D005708), PBS (MESH:D007854), sodium acetate (MESH:D019346), CTMP (MESH:C045337), isocyanide (MESH:D003486), 188Re (MESH:C000615081), risedronate (MESH:D000068296), Bisphosphonate (MESH:D004164), calcium (MESH:D002118), 161Tb-HEDP (-), 103Pd (MESH:C000615531), cisplatin (MESH:D002945), ibandronate (MESH:D000077557), S (MESH:D013455), 3-acetylpyridine (MESH:C010835), pyridine (MESH:C023666), stannous chloride (MESH:C023599), 186Re-MAMA-HBP (MESH:C512982), 68Ge (MESH:C000615436), HEDP (MESH:D012968), 131I- (MESH:C000614965), phenylalanine (MESH:D010649), hydroxyapatite (MESH:D017886), 68Ga (MESH:C000615430), squaric acid (MESH:C030042), 18F (MESH:C000615276), leucine (MESH:D007930), bipyridyl (MESH:D015082), ZOL (MESH:D000077211), terbium (MESH:D013725), 109Pd (MESH:C000615532), tricine (MESH:C100184), 186Re-HEDP (MESH:C101598), thiourea (MESH:D013890), NOTA (MESH:C048993), acetamide (MESH:C030686), scandium (MESH:D012538), pamidronate (MESH:D000077268), 186Re-MAMA-BP (MESH:C512981), tungsten-188 (MESH:C000615076), 177Lu (MESH:C000615061), metal (MESH:D008670), pertechnetate (MESH:D013670), 99Mo (MESH:C000615515), T (MESH:D014316), phosphate (MESH:D010710), P (MESH:D010758), 225Ac (MESH:C000615155), DOTA (MESH:C071349), O (MESH:D010100), 99mTc (MESH:D013667), 90Y (MESH:C000615496)
- **Species:** Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** PC-3 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0035), MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), Balb/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023)

## Full text

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## Figures

20 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12943370/full.md

## References

155 references — full list in the complete paper: https://tomesphere.com/paper/PMC12943370/full.md

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Source: https://tomesphere.com/paper/PMC12943370