Visualization in the ipsilateral lymph nodes secondary to extravasation of a bone-imaging agent in the left hand: a case report

Axillary or elbow lymph node visualization after subcutaneous infiltration of the bone-imaging agent on a routine bone scintigraphy has been reported. The prostate cancer patient in this case report underwent bone scintigraphy; in 3-h bone images, the lymph nodes in the wrist, elbow, and axillary regions were simultaneously visualized. This was caused by extravasation of the intravenous injection of bone-imaging agent in the dorsal part of the patient's hand.     

Clinical evaluation of some phosphorus bone-imaging agents: concise communication.

Four different Tc-99m labeled phosphorus-based bone-imaging agents were compared by a scan-evaluation technique in which the skeletal uptake was visually assessed at selected sites. A detailed statisticalanalysis of scans, by each of three independent evaluators, on a total of 140 different patients showed that two of the agents (based on pyro- and on trimetaphosphate) were superior. The statistical analysis showed good agreement between the investigators and consistency in thier repeat evaluations.     

Skeletal PET with 18F-fluoride: applying new technology to an old tracer.

Although (18)F-labeled NaF was the first widely used agent for skeletal scintigraphy, it quickly fell into disuse after the introduction of (99m)Tc-labeled bone-imaging agents. Recent comparative studies have demonstrated that (18)F-fluoride PET is more accurate than (99m)Tc-diphosphonate SPECT for identifying both malignant and benign lesions of the skeleton. Combining (18)F-fluoride PET with other imaging, such as CT, can improve the specificity and overall accuracy of skeletal (18)F-fluoride PET and probably will become the routine clinical practice for (18)F-fluoride PET. Although (18)F-labeled NaF and (99m)Tc-diphosphonate have a similar patient dosimetry, (18)F-fluoride PET offers shorter study times (typically less than 1 h), resulting in a more efficient workflow, improved patient convenience, and faster turnarounds of reports to the referring physicians. With the widespread availability of PET scanners and the improved logistics for the delivery of (18)F radiopharmaceuticals, prior limitations to the routine use of (18)F-fluoride bone imaging have largely been overcome. The favorable imaging performance and the clinical utility of (18)F-fluoride PET, compared with (99m)Tc-diphosphonate scintigraphy, support the reconsideration of (18)F-fluoride as a routine bone-imaging agent.     

Clinical comparison of bone scintigraphy with 99Tcm-DPD, 99Tcm-HDP and 99Tcm-MDP

The bone-imaging agents MDP, DPD and HDP were compared radiochemically (only minor differences were found) in 12 patients with prostatic and 12 patients with breast carcinoma. Each patient received both MDP and either DPD or HDP. The scintigraphic examinations were compared visually and quantitatively. The uptake ratio normal bone/soft tissue was higher for DPD and HDP than for MDP. The ratio pathologic bone/normal bone was highest for MDP, particularly for prostatic carcinoma. The differences in this ratio for breast carcinoma were in general non-significant. The observed differences were minor and of little practical importance.     

Diffuse pulmonary uptake of 99mTc bone-imaging agents: case report and survey

Over the past 5 years, we have encountered 6 cases of diffuse pulmonary uptake of 99m-Tc bone-scanning agents (incidence, 0.04%). To assess the significance of this phenomenon, we reviewed all of the cases reported since 1974 (Including our series, a total of 32 cases). Three groups can be discerned, the first consisting of 24 patients without radiological calcifications in the lungs and with hypercalcemia of different origins (mostly hyperparathyroidism). Of the eight autopsies performed in this group, seven revealed extensive calcifications in alveolar walls and lung vessels; the other autopsy showed no calcification at all and only bronchopneumonic lesions. The second group consists of 6 patients in chronic dialysis. The last group consists of 2 patients having diffuse pulmonary alveolar microlithiasis with extensive radiologic calcifications. The mechanism of lung uptake of 99m-Tc bone-imaging agents is probably the same as that of bone uptake (chemisorption on hydroxyapatite crystals), although other uptake mechanisms have also been discussed. Bone scintigraphy can be useful in the detection of early pulmonary calcifications, which have been associated with impaired pulmonary function and, due to their size, are generally not detected by X-ray.     

Indium-113m-labeled polyfunctional phosphonates as bone-imaging agents.

Indium-113m complexed with polyfunctional phosphonates EDTMP (an analog of EDTA with carboxylic groups replaced by phosphate groups) and DTPMP (an analog of DTPA) showed preferential skeletal localization in experimental animals. Excellent images of the rabbit skeleton were obtained with both 113mIn and 111In complexes using the scintillation camera. In tissue radioassay using 85Sr as a simultaneous biologic standard, 113mIn-EDTMP compound showed higher concentration in the skeleton than the DTPMP complex and its bone uptake was comparable to that of 85Sr. Renal excretion was greater for the DTPMP complex (70% vs. 50% for EDTMP at 4 hr) and its blood clearance was faster than EDTMP. EDTMP was found to be the superior agent also to two other polyfunctional phosphonates, NTMP and HMDTMP. Because of the excellent skeletal localization with minimal soft-tissue levels, 113mIn-EDTMP may find use in bone scanning in humans wherever 99mTc bone-imaging agents are not available. These compounds may prove useful also in demonstrating acute myocardial infarcts, particularly for repeat studies after 99mTc bone agents have already been administered.     

Diffuse pulmonary uptake of 99mTc bone-imaging agents: Case report and survey

Over the past 5 years, we have encountered 6 cases of diffuse pulmonary uptake of ^99m-Tc bone-scanning agents (incidence, 0.04%). To assess the significance of this phenomenon, we reviewed all of the cases reported since 1974 (Including our series, a total of 32 cases). Three groups can be discerned, the first consisting of 24 patients without radiological calcifications in the lungs and with hypercalcemia of different origins (mostly hyperparathyroidism). Of the eight autopsies performed in this group, seven revealed extensive calcifications in alveolar walls and lung vessels; the other autopsy showed no calcification at all and only bronchopneumonic lesions. The second group consists of 6 patients in chronic dialysis. The last group consists of 2 patients having diffuse pulmonary alveolar microlithiasis with extensive radiologic calcifications.The mechanism of lung uptake of ^99m-Tc bone-imaging agents is probably the same as that of bone uptake (chemisorption on hydroxyapatite crystals), although other uptake mechanisms have also been discussed.Bone scintigraphy can be useful in the detection of early pulmonary calcifications, which have been associated with impaired pulmonary function and, due to their size, are generally not detected by X-ray.     

Rationale for the use of bone scans in selected metastatic and primary bone tumors

Since the introduction of bone scans in 1951, there have been many studies comparing biologic and physical characteristics of new bone-imaging agents and the results of scintigraphy and radiology in large numbers of patients. Relatively speaking, there have been fewer studies detailing the health benefits and financial cost associated with the use of skeletal scintigraphy. This review concerns these aspects in patients with malignancies of various sites and stages. About 2% of patients with stage I or II breast cancer have bone metastases at the time they first present, whereas nearly 28% of patients with stage III disease have bone metastases. A large percentage of patients with initially negative scans develop bone metastases during the first 3--4 yr; many of them develop them within the first 12--18 mo after initial diagnosis. For patients with lung cancer, the use of bone scans in staging their disease is somewhat controversial. Several studies indicate that the yield of positive bone scans may range from as low as 2% to as high as 35%. Data on the use of bone scans in staging prostatic cancer initially are similar to those in patients with breast cancer, that is, yields of 7% in patients with stage I or II disease and a yield of about 20% with stage III disease. Children with osteosarcoma or Ewing's sarcoma rarely have bone disease distant from the site of their primary bone lesion at presentation. However, a large percentage of them (30%--40% or so) develop bone metastases during the follow-up period. As in the case with patients with breast cancer, about half of these bone metastases are evident by 12--18 mo.     

Thoracic vertebral photopenia may predict fatty changes of the corresponding bone marrow following irradiation

We present a patient with unresectable bronchogenic carcinoma who underwent irradiation, then had four consecutive bone imaging studies in a 26-month period. Apparent photopenia of the upper thoracic vertebrae developed within six months after irradiation and became more apparent in the images thereafter. At autopsy a section of the corresponding bone marrow showed extensive fatty changes with very few residual blood vessels. Radiation damage of the vascular networks may significantly reduce the blood supply, when integrity of the blood supply is essential for delivery of a normal bone image by the bone-imaging agent. Interruption of blood supply may cause photopenia, and this interruption plus irradiation to marrow elements may also affect the hematopoietic activity of the corresponding bone marrow. The occurrence of radiation-induced photopenia on a bone-imaging study may indicate fatty changes of the corresponding marrow.     

Abnormally increased uptake in the palm and the thumb as the result of a bone imaging agent injection into the radial artery

The "glove" phenomenon is caused by arterial injection of a bone-imaging agent into the antecubital fossa. The authors describe a patient who incidentally received an arterial injection of bone-imaging agent into the right distal radial artery near the wrist, which resulted in a "hot" palm and thumb. The phenomenon of hot palm and thumb can be explained by normal anatomic-physiologic blood flow after radial artery injection. The radial artery contributes the blood supply to the thumb through the dorsal metacarpal arteries of the first metacarpals, and the dorsal carpal branch of the radial artery, a branch of the interosseous artery, and dorsal carpal branch of the ulnar artery form the dorsal carpal rete. The normal vascular anatomic-physiologic dynamic constituted the mixture and dilution effects after the distal radial artery injection that resulted in hot areas limited to the palm and thumb of the hand on bone scintigraphy.     

Tc-99m methylene diphosphonate versus Tc-99m pyrophosphate: biologic and clinical comparison.

The biologic and imaging characteristics of Tc-99m MDP and Tc-99m PPi were compared in animals and patients using freeze-dried bone-imaging kits. Biodistribution data in rabbits showed Tc-99m MDP had slightly higher bone uptake, significantly lower blood levels, and faster urinary excretion compared with Tc-99m PPi. Duplicate studies performed on ten patients showed the following: (a) blood clearance of Tc-99m MDP was more prompt and complete, resulting in significantly lower blood levels at 4 hr; (b) urinary excretion was greater with Tc-99m MDP than with Tc-99m PPi; and (c) Tc-99m PPi showed significant red-cell labeling, whereas Tc-99m MDP did not. Image quality was generally better with Tc-99m MDP than with Tc-99 m PPi, although there was no obvious difference in diagnostic sensitivity between the two agents.     

99mTc-labelled Cu(I)-EHDP, a potential skeletal imaging agent

99mTc-Cu-EHDP has been prepared with high labelling yield applying for the first time the method of instantly formed cuprous ions in the mixture. A gel chromatography column scanning technique has been used to study the 99mTc fractions in the preparation. The study of the influence of pH-value on the amount of 99mTc-CU-EHDP fraction shows that pH 1.6 - 1.7 gave the best labelling results. The formation rate of 99mTc-Cu-EHDP complex with a high labelling yield was fast and achieved within a few mins. This suggests the reduction of 99mTc-pertechnetate to Tc (IV). The final preparation was found stable for at least 4 hrs after mixing the reactants with the 99mTc-eluate. Comparative biokinetic studies of 99mTc-Cu-EHDP and 99mTc-Sn-EHDP in rabbits and mice showed a high bone uptake and fast elimination of 99mTc-Cu-EHDP from the skeleton. No significant difference was found in the plasma protein binding of 99mTc-Cu-EHDP and 99mTc-Sn-EHDP in rats as assessed by the GCS-technique. Radionuclide imaging in rabbits, using a gamma camera, showed 99mTc-Cu-EHDP to be a good bone-imaging agent.     

Preparation and biological distribution of technetium diphosphonate radiotracers synthesized without stannous ion

Two HEDP complexes of technetium (either Tc-99 or a mixture of Tc-99 and Tc-99m) have been prepared without the use of stannous ion. The first, Tc(NaBH4)-HEDP, is synthesized by reduction of TcO4- with NaBH4 in the presence of excess HEDP; this is analogous to the preparation of Tc(Sn)-HEDP in commercial kits wherein SN(II) functions as the reductant. The second, Tc-HEDP, is prepared by substitution of HEDP onto the pre-formed, pre-reduced, technetium center TcBr62-. The HEDP-to-Tc ratio in Tc-HEDP was found to be 1.0 by double-labeling procedures (Tc-99 and [3H]HEDP), implying that in solution this material is polymeric or at least dimeric. Preparations of Tc(NaBH4)-HEDP and Tc-HEDP with Tc-99m are excellent bone-imaging agents in both rats and dogs. Tissue distribution studies in rats show that uptake of Tc(NaBH4)-HEDP and Tc-HEDP by the bone is at least equivalent to that achieved by Tc(Sn)-HEDP prepared in commercial kits with Sn(II) as the reductant. Tin is therefore not necessary for the bone-seeking properties of Tc(Sn)-HEDP, and the in vivo distribution of a given HEDP radiotracer seems to depend primarily on the presence of the HEDP ligand and not on the exact nature of the technetium complex itself. Synthesis of technetium radiotracers by a substitution route, rather than by redox, is practicable; this route has the potential of introducing hitherto unattainable flexibility and subtlety into the preparation of technetium radiotracers.     

Myocardial and vascular uptake of a bone tracer associated with secondary hyperparathyroidism

A patient on chronic hemodialysis, with secondary hyperparathyroidism was referred for a radionuclide bone-imaging study. Deposition of 99mTc-methylene diphosphonate (99mTc-MDP) was apparent in the myocardium and abdominal blood vessels, as well as in the skeleton by four-color processed scintigraphy. Plain radiographs of the chest and abdomen demonstrated no calcification in the myocardium or abdominal blood vessels. Several possible mechanism for this uptake are discussed briefly.     

Technetium-99m-labeled stannous imidodiphosphate, a new radiodiagnostic agent for bone scanning: comparison with other 99mTc complexes.

Imidodiphosphate (IDP) is an analog of pyrophosphate and diphosphonate, with a P-N-P bond instead of P-O-P or P-C-P. We have labeled IDP with 99mTc quantitatively (98%) using stannous ions as the reducing/complexing agent in a freeze-dried kit form. Radiobioassay of this compound was carried out in rabbits and the results were compared with those of eight other Tc-labeled bone-imaging agents, using the performance of simultaneously administered 85Sr as a reference standard. The 99mTc-IDP concentrated 20% higher in the bone, and its soft-tissue and blood levels were lower than with 85Sr. By comparison, the concentrations in the bone of the other 99mTc agents were 20% less than that of 85Sr. Regarding blood levels, Tc-IDP performed worse than the Tc-diphosphonate but better than the pyrophosphate and the other technetium complexes. Scintillation camera images of 99mTc-IDP in both rabbits and dogs showed excellent details of the skeleton. In a preliminary human study, images with 99mTc-IDP were somewhat inferior to those comparably procured with 99Tc-methylene diphosphonate, but count rates with the IDP complex were about twice those with the MDP compound. Because of its better bone uptake, however, it is suggested that 99mTc-IDP may be clinically useful in spite of its relatively slow blood clearance.     

Myocardial and vascular uptake of a bone tracer associated with secondary hyperparathyroidism

A patient on chronic hemodialysis, with secondary hyperparathyroidism was referred for a radionuclide bone-imaging study. Deposition of ^99mTc-methylene diphosphonate (^99mTc-MDP) was apparent in the myocardium and abdominal blood vessels, as well as in the skeleton by four-color processed scintigraphy. Plain radiographs of the chest and abdomen demonstrated no calcification in the myocardium or abdominal blood vessels. Several possible mechanism for this uptake are discussed briefly.     

Uptake of Tc-99m-PIPIDA in pulmonary metastases from a hepatoma

Metastatic pulmonary nodules from a well-differentiated hepatoma were well demonstrated by a Tc-99m-labeled hepatobiliary imaging agent. Uptake of this type of radionuclide by metastases from a primary hepatic malignancy has not previously been reported. Such radiopharmaceuticals may prove useful in the future as imaging agents for primary hepatobiliary tumors.     

Localization of (99m)Tc HMDP in an extraskeletal myxoid chondrosarcoma: a case report

Extraskeletal myxoid chondrosarcoma of the lower extremity is rare, and slowly progressive. The authors of this article present the case of a man with progressive enlargement of the right thigh that underwent bone scintigraphy. The bone images showed a diffuse, moderate increase in uptake in the swollen right thigh. Despite chemotherapy, the patient died 28 mo later. At autopsy, it was confirmed that he had extraskeletal myxoid chondrosarcoma of the right thigh, which had metastasized to the upper arms, left scapula, lungs, pleurae, and right lower quadrant of the abdomen. The myxoid chondroid matrix, a major feature of the extraskeletal myxoid chondrosarcoma, is thought to account for the localization of the bone-imaging agent.     

The role of nuclear medicine in monitoring treatment in skeletal malignancy

The nuclear medicine bone scan has historically been one of the most common investigations to stage and monitor skeletal malignancy. Current guidelines for using radiographs to assess the response of skeletal metastases to systemic therapy are limited in their ability to give a timely result. Despite some minor limitations caused by the flare phenomenon, skeletal scintigraphy remains widely used for this purpose, both clinically and in trials of new cancer treatments. Nuclear medicine has also played an important role in the posttherapy evaluation of primary bone tumors, both with bone agents and nonspecific tumor agents, such as 201Tl. In the future, it is possible that positron emission tomography radiopharmaceuticals such as 18F-fluorodeoxyglucose may prove to be superior in predicting and measuring treatment response in primary and metastatic bone and bone marrow disease, but further work is required in this area.     

Ultrasonic contrast agents: safety considerations reviewed

Ultrasonic contrast agents are usually comprised of a stabilised shell encapsulating a gas bubble. When these are introduced in the body they increase the acoustic scattering from the tissues through which they pass, and especially from the vasculature. Their primary uses lie in cardiological and oncological imaging. However, these microbubbles have the potential to act as centres for acoustic cavitation activity, and so it is important to consider the safety of their use from an acoustic standpoint. The addition of ultrasonic contrast agents to in vitro suspensions of red blood cells has been shown to lead to haemolysis when the sample is exposed to ultrasound at levels which leave the cells unharmed in their absence. In vivo the infusion of gas bubble contrast agents into experimental animals has been shown to enhance the incidence of petechiae and haemorrhage in the intestine. The Mechanical Index (MI) thresholds for the effects seen in vitro lie within the range of MIs available with diagnostic clinical scanners, but in vivo the thresholds lie at the top end of the exposure levels available clinically. No adverse effects in humans arising from the ultrasonic exposure of these contrast agents have been reported to date.