99mTc-Medronate (MDP)

Background

Bone metastases are common in patients with advanced malignancies. Autopsy series have shown an incidence of approximately 70% in breast and prostate cancer and 35% in lung cancer. Osseous metastases can profoundly influence quality of life and prognosis. Early and accurate detection is important for therapeutic planning, and many imaging modalities can be used for this purpose.

Technetium-99m methylene diphosphonate (MDP) is one of the most commonly used tracers for SS and its mechanism of action involves a complex interaction of bone repair and blood flow. SS targets the bony cortex, binding to the hydroxyapetite produced when the bone attempts to repair damage caused by metastases. As a whole body imaging modality, bone scan is currently the method of choice for detecting asymptomatic osseous metastases during initial staging or restaging of patients with malignancies that produce blastic or mixed bone metastases, such as prostate, breast, and lung cancer. 

Description

^99mTc-Medronate (or ^99mTc-MDP or ^99mTc-Methylenediphosphonate) is a generic SPECT agent to delineate areas of altered osteogenesis.

Clinical applications

MDP like all phosphonate derivatives has a high affinity for hydroxyapatite crystals which form the inorganic structure of the bone tissue. ^99mTc-MDP is therefore, indicated for bone metastases detection, the imaging of altered bone metabolism in primary bone tumors,  the imaging of bone inflammation, bone post-traumatic lesions, rheumatoid lesions or aseptic necrosis as well as the examination of the repair process in damaged bone tissue. In certain cases, ^99mTc-MDP finds some applications in cardiac imaging, but more common tracers have substituted MDP in cardiology. Doses per patient are in the range 10 to 20 mCi.

Availability

^99mTc-MDP is sold under the brand names 6-MDP or 8-MDP kit (Lacomed), CIS MDP (CIS bio, US MA 1979), Draximage-MDP-10 or MDP-25 (Draximage; marketed since 1978), IFE MDP TC.52S (ISOpharma), McK-8, McK-8/3 or PoltechMDP (POLATOM), MDP (ANSTO), MDP (IDB/AAA), MDP (Pars Isotope), MDP (ROTOP), MDP Tc-IK-10 (Izotop), Medrocis (IBA Molecular (Curium); marketed since 1980; EU MA 2002), Medronate kit (Pharmalucence), Medronate Injection (Radpharm Scientific), MON-MDP (Monrol), MPI- MDP (Medi-Physics), Osteolite (Lantheus), ROTOP-MDP (ROTOP), Skeleton (Medi- Radiopharma), Stannous Agent MDP (Mediam), Tc99m-Medronate (Mallinckrodt), TCK-30 (BRIT), Techne^® MDP (Fuji Film), Technefor (DiaMed, Russian MA 1987), Wuxi Jiangyuan.

Formulations that have been withdrawn include: Amerscan Medronate II^® (GE Healthcare; EU MA 1997), AN-MDP (Syncor, acquired by Cardinal Health in 2002), CIS-MDP-NDA and Osteolite (Pharmalucence), Frosstimage MDP (BMS), Lenoscint (MDS Nordion; EU MA 1998), MDP-Bracco™ (Bracco; US MA 1981, discontinued 2015), MDP Multidose (GE Healthcare), MDP Squibb (BMS), Osteolite (Pharmalucence), Solco^® SMDP (Solmed/Sorin), Tc99m-Medronate (Amersham withdrawn 2005), Technescan MDP (Mallinckrodt; EU MA 1987).

In 2020 in the USA, a dose of Medronate is charged around US$ 15.

Competition

MDP is the most useful generic product for bone scintigraphy and all major radiopharmaceutical manufacturers offer this tracer in their catalogues.

There are several marketed agents useful for bone scintigraphy in both SPECT (^99mTc-HEDP, ^99mTc-HDP, ^99mTc-DPD) and PET modalities (¹⁸F-NaF). All of them are generics. Their use is dependent upon local availability and authorizations, as well as price, but it seems that the highest quality of images is obtained with the PET tracer ¹⁸F-NaF, which is also the most expensive.

Comments

New radiopharmaceuticals for therapy in bone metastasized cancers such as ¹⁸⁸Re-HEDP or ¹⁷⁷Lu-HEDP, or even ²²³Ra-Chloride, show a beta emission that provides a signal sufficient for imaging and in certain cases could substitute for the ^99mTc-derivatives in the future.

Note

The company Chengdu Yunke Pharmaceutical Co. Ltd sells a proprietary medronate derivative labeled with Technetium-99 (care! ⁹⁹Tc not ^99mTc), called Yunke (⁹⁹Tc-MDP) for the therapy of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Yunke has been available in China since 1997. It has been proven that ⁹⁹Tc-MDP treatment can inhibit macrophage infiltration together with downregulation of pro-inflammatory cytokines, including TNF-α and IL1-β, ICAM-1, and MMPs. In the past 10 years other applications of this drug have been explored such as treatment of osteoporosis and different diseases involving osteogenesis.

Despite the labeling with ⁹⁹Tc (decay product of ^99mTc and long half-life of 211,100 years), Yunke is not considered by the authorities as a radioactive substance and the doses used are such that the therapeutic effect is mainly due to the biphophonate toxicity. Yunke is definitely not to be considered as a radiotherapeutic agent.

1. https://doi.org/10.1038/bjc.1965.3 ↩︎