Bone scanning: Radionuclidic reaction mechanisms

doi:10.1016/S0001-2998(76)80032-3

Seminars in Nuclear Medicine

Volume 6, Issue 1, January 1976, Pages 3-18

https://doi.org/10.1016/S0001-2998(76)80032-3 Get rights and content

One of the major successes of nuclear medicine in recent years has been the clinical utility of the ^99mTc-Tabeled bone-imaging agents. This article is concerned with the evidence available for the mechanisms by which these and other such radiopharmaceuticals localize at sites in the skeleton.

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Dosimetry of Bone Seeking Beta Emitters for Bone Pain Palliation Metastases
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Citation Excerpt :
Studies demonstrated that diphosphonates strongly bind to calcium phosphates, including hydroxyapatite. Microautoradiographic studies indicated that radiolabeled diphosphonates do not bind to osteoid but within calcified trabecular bone, below the osteoid layer.41 The metabolism of pyrophosphate and diphosphonate showed a chemical bond to the surface of hydroxyapatite.
Amongst cancer patients, bone pain due to skeletal metastases is a major cause of morbidity. A number of beta-emitting radiopharmaceuticals have been used to provide internal radiotherapy of bone metastases and provide palliative pain relief. In this article we describe the different physical characteristics of the various beta emitting radionuclides which have been used in this clinical setting and the potential impact of differences in dose-rate on radiobiological outcomes. A detailed review of the biodistribution of these treatments, based on both in-vivo clinical investigations and post mortem autoradiography assessments is provided. These treatments result in physiological delivery of radiation doses to the target disease as well as to critical healthy organs. Particular attention is paid to the radiation doses received by normal bone tissue, bone marrow as well as metastatic bone disease. The underlying models of radiation transport within bone and bone marrow are reviewed alongside the practical steps that must be taken to acquire and analyse the information require for clinical dosimetry assessments. The role of whole body measurements, blood and faecal assays as well as both planar and tomographic gamma camera imaging are considered. In addition we review the rationale for allocating measured bone uptake between trabecular and cortical bone tissue. The difference between bone volume and bone surface seeking radiopharmaceuticals are also discussed. This review also extends to the development of preclinical models of bone metastases which may inform future dosimetric calculations. Finally, we also present a comprehensive review of the dosimetry of the established treatments ⁸⁹Strontium-chloride; ³²Phosphorus; ¹⁸⁸Rhenium-hydroxyethylidine disphosphonate; ¹⁸⁶Rhenium-1,1-hydroxyethylidene disphosphonate (¹⁸⁶Re-HEDP); ¹⁵³Samarium-ethylenediaminetetramethylene phosphonate; as well as the emerging treatments ¹⁸⁸Rhenium-zoledronic acid; ¹⁸⁸Rhenium-ibedronat; ¹⁷⁷Lutetium-zoledronic acid; and ¹⁷⁷Lutetium ethylenediaminetetramethylene phosphonate. This review highlights not only the inter treatment differences in the radiation absorbed doses delivered to metastatic disease by different radiopharmaceuticals but also the intra treatment differences which result in a large range of observed doses between patients.
Osteomyelitis of the Thumb in a 21-Year-Old Chiropractic Patient: A Case Report
2018, Journal of Chiropractic Medicine
Citation Excerpt :
A radionuclide scan may detect a bone infection as early as 2 days after the onset.18 A positive bone scan does not specifically make the diagnosis but does measure the increase blood flow and reactive new bone formation seen in osteomyelitis.19 Bone scans have a high sensitivity and a poor specificity.
The purpose of this case report is to describe the presentation of a patient with osteomyelitis of the thumb.
A 21-year-old man presented with painful, red, and edematous thumb pain over the anterior and posterior surface for a duration of 4 days. The patient reported no trauma or recent operation. The patient was treated conservatively for capsulitis. The patient’s symptoms worsened within 2 days, and he was referred for additional imaging consisting of a bone scan. The bone scan showed increased uptake, resulting in a change of diagnosis to suspected osteomyelitis. The patient was referred to a medical doctor for care that consisted of antibiotics and physiotherapy.
Despite treatment, the patient had some mild permanent damage to the range of motion of the joint and soft tissue volume loss.
This case demonstrates the importance of considering osteomyelitis as a differential diagnosis. Amputation was avoided for this patient because of the early recognition and referral.
SPECT/CT in Postoperative Foot and Ankle Pain
2018, Seminars in Nuclear Medicine
Citation Excerpt :
However, quality and resolution of both MRI and CT images are often impaired by artifacts from metal implants or even from microscopic metal wear.6 Bone scintigraphy using Technetium-99m-labeled bisphosphonates is performed to evaluate bone pathology on a functional level with the intensity of tracer uptake depending on regional blood flow, osteoblastic activity, and on altered sympathetic nerve supply.7 With regard to the clinical situation, a correlation between bone pain and the degree of radionuclide uptake was described more than 30 years ago.8
Postoperative pain is a clinically relevant issue in orthopedic patients, affecting more than 40% 1 year after foot and ankle surgery. Because of the very complex anatomy with many different joints and several motion axes, clinical examination and conventional imaging are sometimes not sufficient to identify a local pain generator. Local uptake of bone-seeking radiopharmaceuticals is known to correlate accurately with sites of pain generating foci and, thus, bone scintigraphy has been an established method to evaluate these respective patients for many years. However, the specificity is rather low if only planar images are acquired. The development of SPECT and especially of hybrid SPECT and CT imaging has significantly enhanced the specificity of this technique. The combination of both functional and morphological imaging, ideally performed with a dedicated SPECT/CT system to minimize misregistration owing to motion artifacts and to enhance image quality by attenuation correction, allows an early and reliable detection of pathologic bone processes, even in patients where radiological imaging with MRI or CT is hampered by metal implants. In diabetic patients with a neuropathic Charcot osteoarthropathy, infection can be differentiated from inflammatory bone alterations (causing bone marrow edema) almost certainly using SPECT/CT with radiolabeled white blood cells and antigranulocyte antibodies, allowing an individual and precise treatment planning either in the initial course of the disease or even after surgery.
This article reviews the most frequent clinical challenges in patients after foot and ankle surgery, including a description of the various surgical procedures, the different imaging options with their advantages and disadvantages, and aims to integrate bone SPECT/CT into the clinical diagnostic workup.
Semi-quantitative analysis of scintigraphic findings in the hands of adults without osteoarticular disease
2017, Revista Colombiana de Reumatologia
La gammagrafia ósea es uno de los estudios más frecuentemente utilizados para el abordaje diagnóstico de la patología osteoarticular, sin embargo, no se conocen patrones claros de normalidad para algunos sitios anatómicos, llevando a tasas altas de variabilidad interobservador, como es el caso de la evaluación de las manos. No se encuentra en la literatura una descripción del patrón gammagráfico normal sobre manos, por lo cual pretendemos describir el patrón de captación más frecuente en una población adulta sin enfermedad osteoarticular.
Se hizo un análisis prospectivo de 156 gammagrafías óseas sobre manos que cumplieron el criterio de inclusión. Se delinearon regiones de interés en el carpo, metacarpo, articulaciones interfalángicas proximales y distales de los dedos índice y medio de ambas manos; se tomaron las cuentas totales, se analizaron promedios y desviación estándar, y se hizo análisis semicuantitativo de la imagen.
Se incluyeron 36 hombres (23%) y 119 mujeres (77%), la edad media fue de 44,9 ± 13,9. Los promedios de las cuentas totales disminuyeron progresivamente de proximal a distal en todos los grupos de edad y en ambos géneros, siguiendo la siguiente proporción: carpo 4,4 veces más que metacarpo; metacarpo 1,7 veces más que interfalángica proximal; interfalángica proximal 1,4 veces más que distal.
En manos de pacientes adultos, sin enfermedad osteoarticular, sin distinción de género y edad, encontramos un patrón gammagráfico en «degradé» con mayor concentración isotópica en carpo, seguida del metacarpo y de las articulaciones interfalángicas proximales y distales.
Bone and joint disease has a high incidence and impact on the population. The bone scan is a diagnostic tool that provides important metabolic and clinical information, therefore the interpretation of the images by the nuclear medicine physician must be very precise. The isotopic distribution pattern in hands has not yet been described. For this reason a description is presented of common scintigraphic findings in adults without osteoarticular disease.
A prospective analysis was conducted on 156 hands of patients whose bone scans met inclusion criteria. There were delineated regions of interest in the carpal, metacarpal, proximal, and distal interphalangeal joints of the second and third fingers of both hands. An analysis was made, including the total counts, means, and standard deviations. The cut-offs were selected using the normal distribution, which was defined as the cut at the 99th percentile of each variable. A semi-quantitative analysis was made of the images.
The study included 36 men (23%) and 119 women (77%), and the mean age was 44.9 ± 13.9. The mean total counts gradually decreased from proximal to distal in all age groups and in both genders in the following proportions: the activity in carpus was 4.4 fold more than the metacarpus; the metacarpus was 1.7 fold more than proximal interphalangeal joint; proximal interphalangeal joint was 1.4 fold more than distal one.
A scintigraphic pattern consisting of a gradual decrease from proximal to distal joints (degradation) was found in the hands of adults without bone and joint disease, regardless of gender and age.
The bone scan
2012, Seminars in Nuclear Medicine
Citation Excerpt :
Osteoblasts form an osteoid matrix that is later mineralized with hydroxyapatite crystals. 99m-Tc diphosphonates chemisorb6 and bind to the hydroxyapatite crystals in proportion to local blood flow and osteoblastic activity and are therefore markers of bone turnover and bone perfusion. They rapidly localize to bone and clear quickly from background, making them favorable for imaging.
Bone imaging continues to be the second greatest-volume nuclear imaging procedure, offering the advantage of total body examination, low cost, and high sensitivity. Its power rests in the physiological uptake and pathophysiologic behavior of 99m technetium (99m-Tc) diphosphonates. The diagnostic utility, sensitivity, specificity, and predictive value of 99m-Tc bone imaging for benign conditions and tumors was established when only planar imaging was available. Currently, nearly all bone scans are performed as a planar study (whole-body, 3-phase, or regional), with the radiologist often adding single-photon emission computed tomography (SPECT) imaging. Here we review many current indications for planar bone imaging, highlighting indications in which the planar data are often diagnostically sufficient, although diagnosis may be enhanced by SPECT. ¹⁸F sodium fluoride positron emission tomography (PET) is also re-emerging as a bone agent, and had been considered interchangeable with 99m-Tc diphosphonates in the past. In addition to SPECT, new imaging modalities, including ¹⁸F fluorodeoxyglucose, PET/CT, CT, magnetic resonance, and SPECT/CT, have been developed and can aid in evaluating benign and malignant bone disease. Because ¹⁸F fluorodeoxyglucose is taken up by tumor cells and Tc diphosphonates are taken up in osteoblastic activity or osteoblastic healing reaction, both modalities are complementary. CT and magnetic resonance may supplement, but do not replace, bone imaging, which often detects pathology before anatomic changes are appreciated. We also stress the importance of dose reduction by reducing the dose of 99m-Tc diphosphonates and avoiding unnecessary CT acquisitions. In addition, we describe an approach to image interpretation that emphasizes communication with referring colleagues and correlation with appropriate history to significantly improve our impact on patient care.
Synthesis, characterization, and in vivo skeletal localization of a new <sup>99m</sup>Tc-based multidentate phosphonate chelate: 5-Amino-1,3-bis(ethylamine-(N,N dimethyl diphosphonic acid) acetamido) benzene
2007, Bioorganic and Medicinal Chemistry
The tetraphosphonate ligand, 5-amino-1,3-bis(ethylamine-(N,N-dimethyl diphosphonic acid) acetamido) benzene (IPTMP) used in the present study was prepared from 5-nitroisophthalate dimethylester to label with radionuclide for targeted diagnosis and therapy. The synthesized multidentate phosphonate ligand was characterized on the basis of spectroscopic techniques, which exhibited good metal ion control properties when complexed to ^99mTc with high in vitro and in vivo stability. Excellent quality bone images of rabbit were imaged showing rapid clearance of background activity and visualization of skeleton at 1 h.

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⁺: Supported in part by USPHS Grant GM 18674.

¹: From the Department of Radiology, Harvard Medical School and Peter Bent Brigham Hospital, Boston, Mass., and Miami Valley Laboratories, the Procter & Gamble Company, Cincinnati, Ohio.

²: Alun G. Jones, Ph.D.: Associate in Radiology, Harvard Medical School, Boston

³: Mass. Marion D. Francis, Ph.D.: Senior Scientist, Research and Development Department, Miami Valley Laboratories, the Procter & Gamble Company, Cincinnati, Ohio

⁴: Michael A. Davis, Sc.D.: Assistant Professor of Radiology, Harvard Medical School, Boston, Mass.

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Bone scanning: Radionuclidic reaction mechanisms+

Metabolism and homeostatic function of bone

99mTc-labeled polyphosphate as a skeletal imaging agent

Radiology

Optimization of the ratio of stannous tin: Ethane-1-hydroxyl-1,1-diphosphonate for bone scanning with 99mTc-pertechnetate

J Nucl Med

The inhibition of calcium hydroxyapatite crystal growth by polyphosphonates and polyphosphates

Calcif Tissue Res

Technetium-99m-pyrophosphate kinetics and imaging in metabolic bone disease

J Nucl Med

A proposed mechanism for 99mTc-labeled polyphosphate and diphosphonate uptake by human breast tissue

Radiology

Kinetics of calcium and strontium metabolism in man

Bone growth osteoclastic activity as indicated by radiographic distribution of plutonium

Am J Anat

Strontium

Renal excretion of alkaline earths

Intestinal absorption of strontium

The movement in and out of the skeleton

Rare earth nuclides as potential agents for skeletal imaging

J Nucl Med

157Dy-HEDTA for skeletal imaging

J Nucl Med

The formation and influence of surface phases on calcium phosphate solids

Adv Oral Biol

Deposition of radiogallium (72Ga) in skeletal tissues

J Pharmacol Exp Ther

Investigation of 68Ga-tripolyphosphate as a potential bone scanning agent

Int J Appl Radiat Isot

The binding of gallium by blood serum

J Pharmacol Exp Ther

Physiological effects of small doses of fluoride

Distribution, migration and binding of whole blood fluoride evaluated with radiofluoride

Am J Physiol

The effect of enamel fluoride on acid production by Lactobacillus casei

Arch Oral Biol

18F-fluoride for bone imaging

Semin Nucl Med

The chemical form of 18F used in bone scintigraphy

Br J Radiol

18F-Komplex-verbindungen für die Knochenszintigraphie

Nucl Med

Volumetric method for determination of fluorine

Ind Eng Chem, Anal Ed

Knochendiagnostick mit 18F-Natrium-Hexafluoroaluminat

Dtsch Ges Lesen

^99mTc-labeled polyphosphate as a skeletal imaging agent

Optimization of the ratio of stannous tin: Ethane-1-hydroxyl-1,1-diphosphonate for bone scanning with ^99mTc-pertechnetate

A proposed mechanism for ^99mTc-labeled polyphosphate and diphosphonate uptake by human breast tissue

¹⁵⁷Dy-HEDTA for skeletal imaging

Deposition of radiogallium (⁷²Ga) in skeletal tissues

Investigation of ⁶⁸Ga-tripolyphosphate as a potential bone scanning agent

¹⁸F-fluoride for bone imaging

The chemical form of ¹⁸F used in bone scintigraphy

¹⁸F-Komplex-verbindungen für die Knochenszintigraphie

Knochendiagnostick mit ¹⁸F-Natrium-Hexafluoroaluminat