**2. Mechanism and technique of skeletal radionuclide imaging**

Bone scintigraphy is one of the most common investigations performed in nuclear medicine and routinely used in the evaluation of patients with cancer for suspected bone metastases and in various benign musculoskeletal conditions. The uptake of radiotracers in bone is associated with local osteoblastic activity and regional blood flow. More radiopharmaceutical is delivered to hyperemic areas. Either increased blood flow or increased osteogenesis for many types of lesions results in higher tracer uptake than in unaffected or normal parts of the skeleton.

Skeleton System 289

**Z(p) N(n) isotopic mass (u) half-life Decay** 

99mTc 43 56 98.9062547(21) 6.0058 hr IT (99.99%) 99Tc 140.5 keV β-

Upon intravenous injection, the uptake of 99mTc-MDP appears to be related to bone metabolic activity and to skeletal blood flow. 99mTc-MDP exhibits a specific affinity for areas of altered osteogenesis. The adsorption is believed to occur primarily to the mineral phase of bone, with little biding to the organic phase. The uptake is significantly higher in amorphous calcium phosphate than in mature crystalline hydroxyapatite, which helps explain the avidity of the tracer for areas of increased osteogenic activity. Localized areas of decreased skeletal accumulation of 99mTc-MDP may be seen in areas of reduced or absent regional blood flow (i.e. bone infarction) and in areas where the skeleton has been destroyed

99mTc (V)-DSMA and 99mTc-MIBI are usually used in seeking tumors in soft tissues. Also there are reports on the 99mTc (V)-DSMA scintigraphy as a monitor in the response of bone disease to vitamin D3 therapy in renal osteodystrophy and 99mTc (V)-DSMA whole body

Gallium-67 (67Ga) is also a single photon emitting radionuclide; it is an iron analogue which avidly binds to iron-binding proteins. It competes for iron sites in transferring and is absorbed by lysosomes and endoplasmic reticulum of white blood cells. It has been used in the evaluation of unknown original fever, chronic inflammations, detection and localization of osteomyelitis and/or disk space infection, etc. The excitation energy of 67Ga is 93.3 keV (36%) and has a life time of 3.26 days. 67Ga scintigraphy has been used to determine the

Thalium-201 (201Tl) is another single photon emitting radionuclide, it has been used in many different SPECT imaging protocols such as myocardial perfusion imaging, skeleton imaging, tumor positive imaging, parathyroid imaging combined with pertechnetate, etc. 201Tl decays by electron capture and gamma emitter with subsequent gamma emission of 68.9 to 80.3

Although the role of 201Tl scintigraphy for staging the disease of bone tumor and differentiation of benign from malignant lesions is limited, it has provided important information on the management of patients with bone tumors. 201Tl scintigraphy reflects the disease activity after treatment and it should be used to determine the treatment response

PET, which is short for positron emission computed tomography, is the most advanced equipment in the field of nuclear medicine even in the area of image science. Lots of kinds of positron emitting radionuclide have been used in practice, such as 18F, 11C (carbon-11), 15O (oxygen-15), 13N (nitrogen-13), etc. The most widely used radionuclide is fluorine-18 (18F) and carbon-11 (11C). The 18F radiolabelled and 11C labelled skeletal radiopharmaceuticals are used in PET imaging, which reflect the bone metabolism. The following table (table 2)

Table 1. The nuclear physics characteristics of radionuclide 99mTc

to the point that no bone matrix elements are present for uptake to occur.

scan in detection of metastases in thyroid medullary cancer.

treatment response in soft tissue tumors, such as osteosarcoma.

and for early diagnosis of recurrence in bone soft tissue tumors.

keV (94%) and has a life time of 3.04 days.

summarizes their nuclear physics characteristics.

**2.1.2 Positron emitting agents** 

**excitation energy isotope(s)** 

**mode(s)** 

(.0037%) 99Ru

**Daughter** 

**Nuclide symbol** 

The accumulation of radionuclide in bone is related to both vascularity and rate of bone turn over. Increased blood supply to an area of bone result in increased activity in a blood-pool image (obtained immediately after radiopharmaceutical administration).

The localization of various bone imaging agents is related to exchange with ions in the bone. The process of exchange of an ion native to bone for a labelled, bone-seeking ion is termed heter-ionic exchange. Calcium phosphate is the main inorganic constituent of bone; however, calcium is also found in the form of carbonate and fluoride. Calcium is located in microcystals of hydroxyapatite. Analog elements of calcium, such as strontium-85 (85Sr), are believed to exchange with the calcium. Flurorine-18 (18F) exchanges with hydroxyl ion in the hydroxyapatite. The accumulation of labelled phosphate compounds is probably related to the exchange of the phosphorus groups onto the calcium of hydroxyapatite. Although these mechanisms are not completely understood, the principle of bone imaging is fairly basic. Calcium analogs or phosphate compounds have a low concentration in blood and tissues, and this will supply a good bone-to-soft tissue background ratio.

Radiopharmaceuticals used for bone imaging sometimes can localize in soft tissue areas, demonstrating not only calcification but also infarction, inflammation, trauma, and tumor. The portion of any radiopharmaceutical that does not accumulate in bone and tissue or stays in the circulation is eliminated from the body by various routes, depending on the radiopharmaceutical. 85Sr can be concentrated in the gastrointestinal tract for several days. 18F-fluoride (18F-NaF) and phosphate scans labelled with technetium-99m (99mTc) demonstrate activity in the kidneys and bladder, since these agents are excreted through the urinary tract.

### **2.1 Radiopharmaceuticals**

Because of different radiopharmaceutical defining the imaging type, it is necessary to introduce some tracers widely used in clinical departments. Radiopharmaceuticals are classified into three goups; single photon emitting agents, positron emitting agents and therapeutic radiopharmaceuticals according to the radiation types.

#### **2.1.1 Single photon emitting agents**

SPECT, which is short for single photon emission computer tomography, is the most widely used equipment in departments of nuclear medicine. There are lots of different kinds of single photon emitting radionuclides, however not all of them are suitable for skeleton imaging. The most widely used radionuclide is technetium-99m (99mTc).

Technetium-99m is a metastable nuclear isomer of technetium-99, symbolized as 99mTc. Technetium- 99m emits gamma rays which can be detected by SPECT. It is well suited to the role because it emits readily detectable 140 keV (excitation energy) gamma rays, and its halflife for gamma emission is about 6 hr. The short half life of the isotope (in terms of humanactivity and metabolism) allows for scanning procedures. The following table (table 1) summarizes its nuclear physics characteristics.

The agents are composed of radiation emitter and chemical or biologic molecules. The Tc-99m-labelled skeletal radiopharmaceuticals are distributed rapidly throughout the extracellular fluid space. For example, 99mTc-methylene diphosphonate (99mTc-MDP) is the most famous tracer of skeletal imaging, 99mTc (V)-2, 3-dimercaptosuccinic acid (99mTc (V)- DSMA), and 99mTc-sestamibi (99mTc-MIBI) are also used in skeletal and soft tissue tumors imaging.

The accumulation of radionuclide in bone is related to both vascularity and rate of bone turn over. Increased blood supply to an area of bone result in increased activity in a blood-pool

The localization of various bone imaging agents is related to exchange with ions in the bone. The process of exchange of an ion native to bone for a labelled, bone-seeking ion is termed heter-ionic exchange. Calcium phosphate is the main inorganic constituent of bone; however, calcium is also found in the form of carbonate and fluoride. Calcium is located in microcystals of hydroxyapatite. Analog elements of calcium, such as strontium-85 (85Sr), are believed to exchange with the calcium. Flurorine-18 (18F) exchanges with hydroxyl ion in the hydroxyapatite. The accumulation of labelled phosphate compounds is probably related to the exchange of the phosphorus groups onto the calcium of hydroxyapatite. Although these mechanisms are not completely understood, the principle of bone imaging is fairly basic. Calcium analogs or phosphate compounds have a low concentration in blood and tissues,

Radiopharmaceuticals used for bone imaging sometimes can localize in soft tissue areas, demonstrating not only calcification but also infarction, inflammation, trauma, and tumor. The portion of any radiopharmaceutical that does not accumulate in bone and tissue or stays in the circulation is eliminated from the body by various routes, depending on the radiopharmaceutical. 85Sr can be concentrated in the gastrointestinal tract for several days. 18F-fluoride (18F-NaF) and phosphate scans labelled with technetium-99m (99mTc) demonstrate activity in the kidneys and bladder, since these agents are excreted through the

Because of different radiopharmaceutical defining the imaging type, it is necessary to introduce some tracers widely used in clinical departments. Radiopharmaceuticals are classified into three goups; single photon emitting agents, positron emitting agents and

SPECT, which is short for single photon emission computer tomography, is the most widely used equipment in departments of nuclear medicine. There are lots of different kinds of single photon emitting radionuclides, however not all of them are suitable for skeleton

Technetium-99m is a metastable nuclear isomer of technetium-99, symbolized as 99mTc. Technetium- 99m emits gamma rays which can be detected by SPECT. It is well suited to the role because it emits readily detectable 140 keV (excitation energy) gamma rays, and its halflife for gamma emission is about 6 hr. The short half life of the isotope (in terms of humanactivity and metabolism) allows for scanning procedures. The following table (table 1)

The agents are composed of radiation emitter and chemical or biologic molecules. The Tc-99m-labelled skeletal radiopharmaceuticals are distributed rapidly throughout the extracellular fluid space. For example, 99mTc-methylene diphosphonate (99mTc-MDP) is the most famous tracer of skeletal imaging, 99mTc (V)-2, 3-dimercaptosuccinic acid (99mTc (V)- DSMA), and 99mTc-sestamibi (99mTc-MIBI) are also used in skeletal and soft tissue tumors

image (obtained immediately after radiopharmaceutical administration).

and this will supply a good bone-to-soft tissue background ratio.

therapeutic radiopharmaceuticals according to the radiation types.

imaging. The most widely used radionuclide is technetium-99m (99mTc).

urinary tract.

imaging.

**2.1 Radiopharmaceuticals** 

**2.1.1 Single photon emitting agents** 

summarizes its nuclear physics characteristics.


Table 1. The nuclear physics characteristics of radionuclide 99mTc

Upon intravenous injection, the uptake of 99mTc-MDP appears to be related to bone metabolic activity and to skeletal blood flow. 99mTc-MDP exhibits a specific affinity for areas of altered osteogenesis. The adsorption is believed to occur primarily to the mineral phase of bone, with little biding to the organic phase. The uptake is significantly higher in amorphous calcium phosphate than in mature crystalline hydroxyapatite, which helps explain the avidity of the tracer for areas of increased osteogenic activity. Localized areas of decreased skeletal accumulation of 99mTc-MDP may be seen in areas of reduced or absent regional blood flow (i.e. bone infarction) and in areas where the skeleton has been destroyed to the point that no bone matrix elements are present for uptake to occur.

99mTc (V)-DSMA and 99mTc-MIBI are usually used in seeking tumors in soft tissues. Also there are reports on the 99mTc (V)-DSMA scintigraphy as a monitor in the response of bone disease to vitamin D3 therapy in renal osteodystrophy and 99mTc (V)-DSMA whole body scan in detection of metastases in thyroid medullary cancer.

Gallium-67 (67Ga) is also a single photon emitting radionuclide; it is an iron analogue which avidly binds to iron-binding proteins. It competes for iron sites in transferring and is absorbed by lysosomes and endoplasmic reticulum of white blood cells. It has been used in the evaluation of unknown original fever, chronic inflammations, detection and localization of osteomyelitis and/or disk space infection, etc. The excitation energy of 67Ga is 93.3 keV (36%) and has a life time of 3.26 days. 67Ga scintigraphy has been used to determine the treatment response in soft tissue tumors, such as osteosarcoma.

Thalium-201 (201Tl) is another single photon emitting radionuclide, it has been used in many different SPECT imaging protocols such as myocardial perfusion imaging, skeleton imaging, tumor positive imaging, parathyroid imaging combined with pertechnetate, etc. 201Tl decays by electron capture and gamma emitter with subsequent gamma emission of 68.9 to 80.3 keV (94%) and has a life time of 3.04 days.

Although the role of 201Tl scintigraphy for staging the disease of bone tumor and differentiation of benign from malignant lesions is limited, it has provided important information on the management of patients with bone tumors. 201Tl scintigraphy reflects the disease activity after treatment and it should be used to determine the treatment response and for early diagnosis of recurrence in bone soft tissue tumors.
