By Scott Williams, MD

April 3, 2002 --

Technetium-MDP Chemistry & Pharmacology

Bone is a composite material of inorganic crystals bound to protein [4]. The mineral phase, built of crystals containing mainly calcium and phosphate, is called hydroxyapatite and this is bound to a matrix largely consisting of a single protein- collagen [4]. Collagen provides toughness to bone, making it less brittle so that is better resists mechanical stress [4]. Healthy adult bone is in homeostasis- with a constant rate of remodeling due to the activity of osteoblasts laying down new bone and osteoclasts resorbing old bone in response to mechanical stresses [4]. The bone consists of two components- a compact (cortical) component and a cancellous (trabecullar) component that serve different functions [4]. Although cortical bone forms most of the bone mass (80%), it represents a minority of the bone surface which is mostly trabecullar bone) [4].

Technetium-MDP (Methylene diphosphonate) is the agent used for bone imaging (a typical preparation of the radiopharmaceutical is 95% bound to technetium). It is an organic analog of pyrophosphate and contains an organic P-C-P bond. Tc-MDP undergoes protein binding in the blood- only unbound tracer is available for bone uptake [4]. The agent affixes to the bone surface by the process of chemisorption- attaching to hydroxyapatite crystals in bone and calcium crystals in mitochondria. After administration, it is postulated that Tc-MDP dissociates into its technetium and MDP moieties which are then adsorbed onto the organic and inorganic (hydroxyapatite) phases, respectively [2]. About 40-50% of the compound will be affixed to bone by 3 to 4 hours after injection. The adsorption of Tc-MDP to hydroxyapatite appears to increase at low Ph [4].

Excretion is primarily renal [4] and 70% of the administered dose is eliminated by 6 hours. For an adult patient, the usual dose is 20 to 25 mCi. The whole body dose is 0.01 rad/mCi; the urinary bladder is the critical organ, receiving about 0.1-0.2 rad/mCi. The radiation dose from a Tc-MDP bone scan is approximately 4.2-5.3 mSv (420 mrem) [3,4].

The mechanism for increased uptake (increased activity) of the tracer in osseous lesions is multifactorial:

  • Increased blood flow: Bone in hyperemic regions is exposed to more tracer over any given time period. Because the extraction of the radiotracer is non-linear and tends to plateau, increased flow will only result in an increase in bone activity compared to normal bone of about 1.5 to 2 times.
  • Areas and rate of new bone formation (surface area): In these areas there is increased osteoid formation and increased mineralization of osteoid. Newly forming hydroxyapatite crystals are of smaller size than mature crystals and provide a greater surface area for binding.
  • Interruption of sympathetic supply: See Reflex Sympathetic Dystrophy discussion.


(1) Radiographics 2003; Love C, et al. Radionuclide bone imaging: an illustrative review. 23: 341-358

(2) J Nucl Med 1993; Jan.: p.104

(3) J Nucl Med 2009; Iagaru A, et al. Novel strategy for a cocktail 18F-fluoride and 18F-FDG PET/CT scan for evaluation of malignancy: results of the pilot phase study. 50: 501-505

(4) J Nucl Med 2013; Wong KK, Piert M. Dynamic bone imaging with 99mTc-labeled diphosphonates and 18F-NaF: mechanisms and applications. 54: 590-599

Copyright © 2002

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