RADIOISOTOPE SCAN IN BONE & JOINT DISORDERS

By-
Dr. G. N. Mahapatra,
Consultant & Chief, Dept. of Nuclear Medicine & RIA,
Lilavati Hospital, Bandra, Mumbai - 400 050.

Bone scanning has been done with a variety of tracers in the past 30 to 40 yrs. Demonstrating
metastatic disease, primary tumors infections, injuries and a wide variety of other diseases & c
onditions far sooner than conventional x-rays. The unique advantage on bone scan over others
is of its increased sensitivity in detecting early disease process which looks normal in
conventional X-ray or a lytic lesion in CT scan where the entire skeleton is surveyed at a
reasonable exposure.

Radio Pharmaceuticals

I. Technetium MDP (Methylene Diphosphonate)

II. Thallium - 201

III. Gallium - 67

IV. I-131 /-MIBG, I-123

V. Tc-99m labeled leucocyte scan

Tc - 99 MDP Bone Scan

We currently use Tc-99m - Methylene Diphosphonate (MDP) or HDP (hydroxy diphosphonate)
which provide excellent images because of the greater information density afforded by our ability
to give larger doses of Tc99m because of its favourable physical characteristics.

The Tc99m phosphate bone seeking agents depend on intact blood supply & osteogenic activity
of the bone for lcoalization. Images made several hours after injection provide a physiologic map
of the distribution of osteogenic activity in the body & allow early detection due to an underlying
feature of skeletal pathology that the bones react to a wide variety of disease & conditions with
an osteogenic response. Fig. - 1 demonstrates a physiological distribution of the radiotracer in
the skeletal system in the anterior & posterior projection. The various approaches for bone
imaging is routinely done following IV administration of a Tc99m Phosphate bone seeking
radiopharmaceuticals include whole body imaging or spot planar images made 3 to 4 hours
after the injection, vascular flow studies made during injection followed by early post static
imaging made within a min. or so after injection showing relative hyperemia. SPECT reconstruction
slices increase the further sensitivity and spatial localization.

Various Indications of MDP Bone Scan

I. Primary bone tumors e.g. Osteosarcoma, Ewings sarcoma etc.

II. To rule out metastatic bone disease following primary Ca e.g. Cabreast, Ca lung, Ca prostate etc.

III. Avascular necrosis of femoral head.

IV. Bonecyst.

V. Bone infection such as osteomyelitis.

VI. Stress fracture or following vehicular accident with normal conventional x-ray findings.

VII. Metabolic bone disease such as Paget's disease, Osteomalacia, Hyperparathyroidism, renal osteodystrophy, hypertrophic pulmonary osteoarthropathy.

VIII. Compression fracture of the spine.

IX. Leg perthe's disease.

X. Sacroillitis.

Thallium-201 Whole Body Imaging

THALLIUM-201 is a potassium analogue & is take by active tumor cells. It is particularly useful in
detecting brain tumors in equivocal MRI scans & differentiate tumor recurrence from radiation necrosis.
This technique is useful in detecting occult metastatic lesion also in the bone. Apart form its use it can
also differentiate the prosthetic infection from prosthetic loosening in the case of following hip
or knee joint replacement surgery.

L-131 MIBG Whole Body Scan Imaging

500-600 micro curie I-131 MIBG ( Metaiodo Benzyl guanidine ) is injected in I. V. route
& 24 hrs, 48 hrs following injection the whole body imaging is carried out. If any lesion
especially in the diagnosis of disseminated malignant pheochrocytoma affecting the bones
can be revealed with greater specificity & sensitivity.

Gallium-67 Whole Body Imaging

Gallium 67 citrate is a cyclotron produced Gamma emitting radiotracer with a half life of 3 days.
Gallium is useful for imaging areas of infection, inflammation & tumors. Patients may be imaged
at 24 hrs., 48 hrs. & 72 hrs. post injection.

Infected hip/knee prosthesis can be scanned with gallium-67 usually in conjunction with a
MDP bone scan. In an infection of greater than 14 days/2 weeks duration, Ga-67 is useful or less than 14 days / 2 weeks, technetium-99 m labelled white cells scanning is mre appropriate.

In case of long standing Osteomyelitis , in conjunction with a bone scan. Gallium is very useful in assessing active infection on going bone modeling.

In case of neoplasia especially lymphoma, Gallium -67 is useful for diagnosis, stagin & follow up particularly mediastinal lymphoma after radiotherapy to detect the presence of viable tumor or recurrence which is difficult on CT or MRI scan. Bone lymphomas are also detected with greater specificity in junction with baseline MDP bone scan.

Tc-99 m HMPAO Labeled Leucocyte Scan

This is a novel technique of labeling white blood cells in vitro with Tc99m pertechnetate by the help of lipophilic compound i.e. HMPAO (Hexamethy1 propylene amine oxime). the invitro labeling procedure takes about 40-45 mins. After which it is injected in slow IV infusion which can localize the focus of active infection such as Acute from chronic osteomyelitis, prosthetic infection from loosening in hip or knee replacement surgery etc. The sensitivity & specificity in localising the focus of infection is 98% & 99% respectively.

Malignant / Benign Bone Lesions (1&3 ANSWER HERE)

Bone scan is very sensitive for detecting both primary & secondary bone tumors. In the case of breast & prostate bony secondry, the bone scan can be positive some months before plain film radiology. Bone scan is also very sensitive for benign bone lesions such as Osteoidosteoma & osteochondroma.]

Bone Infection
Osteomylelitis

Bone scanning will detect changes early as 24 hrs. after the onset of symptoms. Plain films of radiology can take upto 10 days to detect changes. Particularly useful in children & in differentiating between osteomylitis & cellulitis.

Septic Arthritis

Characteristic particular bone changes ( increased rim of uptake of radiotracer at its periphery with central cold area ) will differentiate osteomyelitis from septic arthritis.

Arthritis

Characteristic increased uptake of the radiotracer in involved aras will disclose early disease prior to x-ray changes. Useful for differentiating between active & inactive disease. Very sensitive in detecting early sacroilitis.

Avascular Necrosis

Avascular necrosis (AVN) affects both children (leg-perthes) and adults. Various etiologies of AVN include trauma (30%-50% femoral neck fractures lead to AVN), steroids, alcohol, pancreatitis, haemoglobinopathies (i.e. sickle cell disease, polycythaemia etc.), Gaucher's disease. Although the disease mechanism is not worked out, some proponents suggest that fat embolism is a common denominator, Fat emboli from fatty liver, destabilization and coalescence of plasma lipoproteins and or disruption of fatty bone marrow and other fat deposits are three mechanisms by which AVN can occur.

The central factor in AVN is vascular insufficiency form occlusion leading to cellular anoxia & death of haemopoitic cells at 6-12 hrs., osteocytes and other bone cells at 12-48 hrs. and marrow fat cells at 2-5 days. Usually the femoral head cartilage is not acffected because it is avascular.

Three phase bone scan in acute phase shows reduction of blood flow through the artery of the affected joint and the head of the bone. With the same pattern in immediate post static image followed by cold are in the joint and the head of the bone in 4 hrs. static delayed images. In recovery phase from the acute reduction of blood flow in avascular necrosis (AVN); the pattern of diagnosis of AVN changes in three phase bone scan. In the early vascular phase reduction of blood supply through the involved artery may not be there. However immediate post static image shows cold area in the affected joint & the head portion of the bone. However delayed static images shows an increased area of tracer accumulation in the trochanteric & neck region of the head suggesting scan evidence of revascularization. If it is associated with fracture neck of femur with the scan evidence of revascularization, then the chance of healing by natural osteoblatic activity is bright as compared to the area of involvement having no sign of revascularization where prosthetic hip or knee replacement will be the treatment of choice.

Sport Medicine

Bone is very sensitive for early periostitis in sports people. Stress fractures particularly of the tibia & metarsals show up abnormal area of accumulation of the radiotracer before x-ray changes. On plain x-rays 50% of tibial stress fractures are not detected. Scaphoid fractures & fractures of the neck in the elderly are usually very difficult to detect with plain x-rays. Bone scanning is very sensitive in both these areas.

Compression / crush fractures in osteopenia : the bone scan is useful to differentiate between new & old fractures.

Fractures in small children ( battered baby syndrome ). The bone scan is very sensitive for small fractures & the whole body can be scanned with very little radiation exposure compared with multiple x-rays.

Metabolic Bone Disease

Tc99MDP bone scanning has great potential in the diagnosis & investigation of metabolic bone disease such as hyperparathyroidism, osteomalacia, renal osteodystrophy & hypertrophic pulmonary osteo arthropathy etc.

It can help in screening for the presence of metabolic bone diseases, assessing the severity of known disease & following the effects of therapy.

Osteomalacia ( softening of the bone ) is characterised by failure of the osteoid matrix to calcify & form bone as a result of an associated or relative deficiency of vit.D. The bone scan appearances in osteomalcia strongly suggest the presence of a metabolic bone disorder. There is a generalised increase in the tracer uptake in the skeleton producing "super scan" with non-visulisation of kidneys. the axial skeleton, long bones, periarticular aras and manible appear prominent. The costo-chondral junction appears prominent showing arosary head appearance on the scan. A characteristic appearance of the sternum may be seen du to increased accumulation which is described as "neck tie sign". Pseudo fractures are common in severe osteomalacia.

Renal Osteodystrophy

Renal osteodystrophy is a common consequence of chronic renal failure. Due to impaired renal conversion of 25-hydroxy cholecalciferol to I-125-dihydroxy cholecalciferol ( the active metabolic of vit. 'D') there is malabsorption of calcium & compensatory hyperparathyroidism. Hence the lesions in renal osteodystrophy are a mixture of osteomalacia, osteitis fibrosa, osteosclerosis & osteoporosis.

The calvaria & mandible are particularly prominent. The tracer uptake intensity is highest in renal osteodystrophy, costo-chondral junction beading & neck tie sign on the sternum are commonly seen. Renal images are not visualised.

Primary Hyper Parathyrodism

Has a wide clinical spectrum of which bone involvement is only one fact. Patients with primary hyperparathyroidism may have bone scan ranging from normal to those found in renal osterodystrophy depending upon the severity of the bone disease. Focal hot spots may be due to vertebral collapse, ectopic calcification of bone cysts.

Paget's Disease

In India we see this condition extremely uncommonly. In general, bone scan is able to detect Paget's bone involvements more easily than Radilogy. Quantitative determination of Tc-99m MDP uptake in assessing response to treatment show good correlation with fall in urinary hydroxy-proline excretion & serum alkaline-phosphatase.

Hypertrophic Osteroarthopathy

Hypertrophic osteoarthropathy is a characteristic clinical syndrome of osteoarthropathy due to various pulmonary & non-pulmonary disorders. Hypertrophic osteoarthropathy remains unknown, endocrine substances such as oestrogen, adreno corticotrophic hormone (ACTH) & growth hormone (GH) secreted by pulmonary cancers, are considered possible causes. Bone scintigraphy using Tc-99m phosphate complexes is a sensitive method of detecting hypertrophic osteoarthropathy. It shows intense symmetrical uptake in the distal protions of the long bones, patellae, feet & phalanges of the hands. A linear increase in the MDP uptake along the cortical margins of the distal femur, tibia & fibula. X-ray findings of the extremities show a periosteal reaction with subperiosteal bone formation. Serum growth hormones are elevated which may be caused by ectopic growth hormone secreation from the pulmonary tumor.

Joint Sciontigraphy

Radio nuclide joint imaging has evolved slowly over the last two decasdes into a clinically useful method of diagnosis & chronologic evaluation of joint desease. It remains unquestionably important that skeletal scintigraphy reveals osseous alterations earlier than radiological procedures. The x-ray shows morphological changes where as the scintigraphy ( as funtion tomography ) makes metabolic change visible. Utilised radiopharmaceuticals (Tc-99m ) Technetium MDP or different phosphate complexes labelled Tc99-m methylene diphosphonate is a bone seeker which attaches it self to calcium deposits. The linked radio nuclide (Tc-99m) ( physical half life 6 hrs. ) makes the ditribution visible. Every wher that there is increased osseous tumor occurring ( as also in arthrosis & in tumors ), MDP shows pathologically increased concentration of activity. 2 to 3 hrs. after IV injection of the radio pharmaceuticals is the best time to make bone scintigraphy ("late phase"). In the joints, a pathological accumulation in the late phase speaks for arthrosis.

However, more intresting for the indication fo radiosynoviorthesis is the "early phase" ( soft tissue scintigraphy ), if joint images are produced approximately 10 mins. after the injection, it has not yet arrived in the bone. The images represent the distribution in the blood pool & the soft tissues. If there is an inflammation of the articular mucosa (synovitis) with the connected hyperaemia, accordingly an increased concentration of activity is shows; Arthritis.

If immediately after injection images in quick sequences are made (dynamic scintigraphy), the initial blood flow of the pictured region is demonstrated ( radio nuclide angiography ).

Combining these three phases in one study it is termed triple phase scintigraphy or multiple phase scintigraphy. Triple phase scintigraphy includes therefore

  • Phase one : Radio nuclide Angiography
  • Phase two : Early phase or blood pool phase soft tissue scintigraphy.
  • Phase Three : Late phas skeletal ( bone ) scintigraphy.

With the help of the ROI ( region of interest ) technique, it is possible to estimate quantitatively the proportion of arthrosis versus arthritis.

The triple phase scintigraphy is the best way of documenting the arthritic / arthrotic conditon of a joint so that it is desirable to do before performing the radiosynoviorathrosis.

In practice however the phase 2 ( soft tissue scintigraphy ) study is sufficient, since it is evidence of arthritis that serve as an indication for radiosynoviorthesis.

To determine indicaiton for radiosynviorathrois in activated arthrosis. It is important to compare the arthrosis component with the arthritis componene. Only with the proof of a clean synovitis ( Phase - 2 scintigraphy ) through scintigraphy does radiosynoviorthesis seems promising & therefore indicated. Frequently this late phase can be froegone, if actual X rays shows the osseous changes.

Radio Synoviorthesis

The term radiosynoviorthesis was first used by Delbarre et al 1968. This means the restoration ( orthersis ) of the synovia by radionuclides. Through local application of radioactive agents, an attempt is made to influence the synovial processes favourabley as an alternative to surgical synovectomy.

At first ( 1963 ) the radionuclide Gold-198 in the colloidal form was used for radiosynoviorthesis, especiall of the knee joints. However because of the unwanted whole body radiation does through the gamma ray component & due to it sspread to lymph nodes & liver, it has been abandoned.

Presently Beta emitting radionuclides are used, also have no or only a minimal gamma ray component. For radiosynoviorthesis isotopes are applied decaying by emitting beta energy. The characteristics of Beta particle are a) the Beta particle energy should be suffecient to penetrate & able the synovial tissue but not so great as to damage underlying articular cartilage or undrelying skin. b) the radionuclide should be attached to particles which are sufficiently small to be phagocytosed but not so small that they might leak from the joint before that occurs. The appropriate range is 2-5 um c) the particle should be biodegradable, because otherwise granulomatous tissue could be induced.

Various radionuclides are available for radiosynoviorthesis. Their selection depends on the size of the joint planned to treat, the smaller the joint, the shorter the radiation penetrating distance.

Yttrium-90 Rhenium-186 Erbium-169 Physical Half life 2.7 days 3.7 days 9.5 days Radiation Beta Beta & Gamma Beta Beta energy (me V) 2.26 0.98 0.34 Tissue range (mm) Max 11.0 3.7 1.0 Mean 3.6 1.2 0.3 Compound Citrate Sulfide Citrate

 

Large Medium Small Joints Knee Shoulder Elbow MCP Wrist PIP Hip DIP Superior & Inferior MIP tarsal joint

Mechanism of Action

Yttrium-90 in colloidal suspensions is formed after phagocytosis especially in the superficial but also relatively seen in the somewhat deeper layers of the synovia, however rarely in the cartilage area.

By arthroscopy in humans after Yttrium-90 injection, a depletion in the number & size of synovial villi with decreased hyperemia is formed early, although histologically often a thickening of synovium occurs. Later sclerosing & fibrosing processes of the synovial villi stroma & of the vessels predominate along with a minimal diffuse damage of articular cartilage. Filtration & Resorption of the synovial fluid are reduced.

A few months later mononuclear cell in the synovia have disappeared & with effecitve treatment the synovium is fibrosed. With selective synovia radiation with beta rays, the expected absorbed dose is approximately 7000 to 10000 rad. This produces necrosis of the cells & decrease of the inflammatory cell proliferation. The synovium becoems more & more fibrosed & the disease's destruction will be stopped.

Dosage

It is impossible to calculate precisely the radiation dose absorbed by the synovium. The effective dose depends not only on the particularly isotope & the injected amont but also on numerous other parameters partially interdependent & difficult to quantify.

  • Size of the joint space.
  • Synovial thickness.
  • Synovial strcture ( smooth, cushioned like, fine or rough villous, edematous, coarse )
  • Distribution with the joints.
  • Colloidal absorption in the joint fluid
  • Condition of the joint fluidI
  • nflammatory activity of the synovitis

For the radiosynoviorthesis of the knee joint normally 185 MBq ( 5mCi( Yttrium-90 are applied. All radionuclide have to be tagged with colloid to avoid rapid leaage from the joint. Radiochemical purity must be guarnteed by the supplying company. The maximum total dose should not exceed 20 mCi in a year & per treatment no more than 10 to 12 mCi should be applied. Multiple joints can be treated simultaneously up to a total activiy 400 MBq per session

Yttrium -90 (90Y)

Yttrium citrate or silicate (90 Y colloid) injection solution. Yttrium-90 decays more that 99% by emission of beta particles with an energy of 2.279 meV.

Yttrium citrate & Yttrium siliate are available & that is decisive for the intraarticular application in colloid form ( particle size about 10mm. ) the smaller the particle size the mroe homogenous the distribution in synovial fluid, the larger the particle size, lesser the lymphatic removal. The yttrium micells are fixed in the synovium by colloidopexy.

(90Y) Yttrium is only used for radio synoviorthesis of knee joints.

Rhenum - 186

(186 Re) Rhenium sulfide or 186 Re colloid injection suspension decays under emission fo B-rays. Rhenium sulfide is applied as a colloid with particle size of 5 to 10mm. It is used for Radiosynoviorthesis of the shoulder elbow, wrist , hip & tarsal joints.

  • Recommended dose : Shoulder joint 74 MBq
  • Elbow joint 55.3-74 MBq
  • Wrist joint 55.3-74 MBq
  • Hip joint 185 MBq
  • Superior tarsal joint ankle 74 MBq
  • Inferior tarsal joint 37 MBq
Erbium

(169 Er) Erbium citrate (169 Er-colloid) It decays under emission of beta particles to stable thulium-169. The beta radiation is useful for therapy as maximum .34 Mev. The gamma radiation of 80 Kev is negligible, though is uded for post theraputic distribution scintigraphy. The maximum range is soft tissue is 1 mm, in cartilage 0.7 mm. 169-Er is uded for radiosynoviorthisis of the small joints as the metacarpo phalangeal joints (MCP), the proximal interphalangeal joints (PIP) & the metatarso phalangeal Joints (MTP). Additionally the distal interphalangeal joints (DIP) & tarsometatarsal joints, the thumb base joints can be treated with 169-Er erbium as well.

After the intraarticular injection of 169-Er erbium colloid the radio pharmaceutical is absorbed by the superficial synovial cell lining. The pharmacokinetic is determined by the particle size of the colloid which is in general about 10 mm.

  • DOSE : Thumbs base = 30 MBq
  • MCP = 22 MBq
  • PIP = 18.5 MBq
  • DIP = 15.0 MBq
  • Tarsometatarsal Joint = 22.0 MBq
  • MTP = 30.0 MBq.