1. SKELETAL RADIONUCLIDE IMAGING IV Dr. Hussein Rabie Farghaly Nuclear Medicine Consultant PSMMC

2. CONTENTS Bone and BM physiology & anatomy Bone scan Radiopharmaceutical, preparation, uptake and pharmacokinetics dosimetry, protocols, normal and altered distribution Clinical indication and Skeletal pathology Bone Marrow scan

3. Soft-tissue uptake in radionuclide musculoskeletal imaging Etiologies of true radiopharmaceutical soft-tissue uptake: 1. metastatic calcification, 2. dystrophic calcification, 3. metabolic uptake, 4. compartmental sequestration. 5. Spurious or artifactual

4. A superscan is intense symmetric activity in the bones with diminished renal and soft tissue activity on a Tc 99 m diphosphonate bone scan This appearance can result from a range of aetiological factors: diffuse metastatic disease –prostatic carcinomaprostatic carcinoma –breast cancerbreast cancer –transitional cell carcinoma (TCC)transitional cell carcinoma (TCC) –multiple myeloma (some difference in opinion)multiple myeloma –lymphomalymphoma patchy uptake nonetheless : look at skull and ribs tends to somewhat spare the distal skeleton metabolic bone diseases –renal osteodystrophyrenal osteodystrophy –hyperparathyroidism 1 (often secondary hyperparathyroidism)hyperparathyroidism –osteomalaciaosteomalacia will involve distal skeleton smoother uptake myelofibrosis / myelosclerosis mastocytosis wide spread Paget's diseasemyelofibrosismastocytosisPaget's disease Superscan

5. Differential Diagnosis of a Cold Defect

6. Imaging Findings in Specific Tumors Breast Carcinoma: local invasion of the ribs Disseminated disease. Another important pattern to recognize is involvement of the sternum via the internal mammary nodes (>80%). Metastatic disease to the soft tissues may be seen increased uptake malignant pleural effusions. Tc-99m MDP uptake in hepatic metastasis in breast cancer.

7. Lung Carcinoma - Appendicular involvement is more common with aggressive lung cancer than cancer of the breast or Prostate: Interesting patterns of disease may occur on scintigrams in lung cancer. Because these tumors can easily invade the vasculature, arterial metastases are more common. These tumor emboli can reach the distal extremities. - Also, a characteristic periosteal change is seen in lung cancer due to hypertrophic osteoarthropathy. This is most often seen as linear, parallel “track” uptake in the medial and lateral margins of the long bones, but may be patchy or show skip areas. The patella, scapula, skull, clavicles, and hands and feet may be involved.

8. Neuroblastoma: has a neural crest origin and is the most common solid tumor to metastasize to bone in children. Tc-99m MDP scintigraphy is twice as sensitive as radiographs on a lesion-by-lesion basis. MRI better determines the extent of a lesion than bone scan. I-131 or I-123 MIBG scanning is more sensitive than bone scan for metastases, although the combination of both gives the highest sensitivity. Lesions are typically multifocal and in the metaphyses. However, involvement in the skull, vertebrae, ribs, and pelvis is also common. Early involvement may be symmetric and therefore difficult to diagnose on the bone scan due to the normal intense activity in the ends of growing bones. A unique characteristic of neuroblastoma is the avidity of Tc-99m diphosphonates for the primary tumor. Approximately 30–50% of primary tumors are demonstrated scintigraphically. Occasionally, neuroblastoma are discovered in children undergoing radionuclide imaging to evaluate another condition. Particular attention should be paid to the abdomen Bone metastases in neuroblastoma

9. Other Tumors of Epithelial Origin The sensitivity for renal cell carcinoma is low and best assessed on skeletal survey or by MRI. Likewise, thyroid cancer is rarely detected on skeletal scintigraphy and is better evaluated with iodine-131 or, if noniodine avid by F-18 FDG PET. Gastrointestinal tract and gynecological cancers do not commonly metastasize to bone early in their courses. Late disease involves bone by direct extension.

10. Primary Bone Tumors Malignant Bone Tumors: Primary bone tumors have avid uptake of the bone-seeking Radiopharmaceuticals. These tumors include the primary neoplasms, osteosarcoma, Ewing’s sarcoma, and chondrosarcoma. However, skeletal scintigraphy is seldom used in the workup of primary bone neoplasms because it does not address the questions the orthopedic surgeon needs answered: assessment of soft tissue extension or definition of tumor margins. MRI is the primary modality for osteosarcoma evaluation. Although most primary bone tumors are monostotic, the occasional polyostotic involvement would be missed without a whole body survey of some kind. Both thallium-201 and technetium-99m sestamibi have been used for sarcoma imaging. They may help to determine if the primary tumor is high- or low-grade and serve as a baseline so that it can be used to evaluate response to therapy. The increased uptake in FDG PET of high-grade tumors has been investigated but has not found a significant clinical role.

11. Osteosarcoma of the right distal femur. The degree of tracer accumulation in the lesion is striking. The increased blood flow induced by the osteosarcoma results in increased tracer delivery to the entire limb. This “extended”or augmented pattern of uptake adds to the difficulty in using the skeletal scintigram to determine the margins of primary bon tumors. (The focal activity over the right ribs is a marker.) A, Osteosarcoma of the left distal femur and a metastatic lesion in the left proximal femur. B, CoronalT1- weighted MRI. it missed the second lesion in the proximal femur which was out of the field of view.

12. Multiple Myeloma The most common primary bone tumor in adults is multiple myeloma. It is a tumor of the marrow and typically involves the vertebrae, pelvis, ribs, and skull. Radiographs may only show osteopenia or a permeative pattern that can be confused with metastatic disease. Although bone scan will show some of the lesions as areas of decreased and sometimes increased uptake, radiographs are more sensitive overall for detecting disease. The lower sensitivity of bone scan relates to the lack of reactive bone formation in response to the lesions. Leukemia Bone scan plays a very limited role in the evaluation of leukemia. Patients with leukemia imaged with Tc-99m MDP may show focal increased uptake in areas of marrow infiltration. In blast crisis, diffusely increased uptake that is greater at the ends of the long bones may be present. Lymphoma Hodgkin’s disease will involve the skeleton approximately one third of the time and the bone scan may show focal or diffuse uptake of Tc-99m MDP. Skeletal scintigraphy is less useful in non- Hodgkin’s lymphoma. In general, lymphoma is best evaluated with gallium-67, F-18 FDG PET/CT. Histiocytosis The sensitivity of bone scan varies with the spectrum of disease in histiocytosis. Although uptake is reliably seen in eosinophilic granuloma, detection of histiocytosis is limited, with lesions seen from one-third to two thirds of the time. Frequently, decreased uptake is shown.

13. Benign Bone Tumors Usually, benign bone tumors are characterized by their radiographic appearance. The role of skeletal scintigraphy is very limited in general, although understanding is critical as benign tumors may be encountered during imaging for other reasons. Some benign tumors have intense uptake similar to malignant tumors. These include osteoid osteomas, giant cell tumors, and fibrous dysplasia. Most benign bone tumors are variable in appearance.

14. Benign Bone Lesions on Skeletal Scintigraphy

15. Osteoid osteoma: pinhole images. Internal and external rotation pinhole spot views of the proximal femur in a patient with suspected osteoid osteoma. An area of abnormally increased uptake demonstrated just lateral to the lesser trochanter confirms the clinical suspicion. Conventional tomogram of the right proximal femur reveals a characteristic radiolucent nidus surrounded by sclerotic bone