JNM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brenner, W.
Right arrow Articles by Henze, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brenner, W.
Right arrow Articles by Henze, E.
Journal of Nuclear Medicine Vol. 44 No. 2 247-251
© 2003 by Society of Nuclear Medicine

Basic Science Investigations

Bone Uptake Studies in Rabbits Before and After High-Dose Treatment with 153Sm-EDTMP or 186Re-HEDP

Winfried Brenner, MD, Willm Uwe Kampen, MD, Corinna Brümmer, MD, Corinna von Forstner, MD, Maaz Zuhayra, PhD, Norbert Czech, MD, Claus Muhle, MD and Eberhard Henze, MD

Clinic of Nuclear Medicine, University Hospital Kiel, Kiel, Germany


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
The aim of this animal study was to measure the bone uptake of 99mTc-hydroxymethylene diphosphonate (HDP) before and after high-dose treatment with 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) or 186Re-(tin)1,1-hydroxyethylidene diphosphonate (HEDP) to prove or disprove post-therapeutic alterations of bone uptake of radiolabeled bisphosphonates. Methods: Quantitative bone scanning using 100 MBq 99mTc-HDP was performed on 12 rabbits before and 8 wk after radionuclide therapy with 1,000 MBq of either 153Sm-EDTMP or 186Re-HEDP. Whole-body images were acquired at 3 min, 3 h, and 24 h after injection, and the activities for the whole body, urinary bladder, and soft tissue were measured by region-of-interest technique. From these data, bone uptake was calculated as initial whole-body activity minus urinary excretion and remainder soft-tissue activity. Results: In animals treated with 153Sm-EDTMP (n = 6), no differences could be proven for the bone uptake of 99mTc-HDP at 24 h after injection before and after therapy (51.1% ± 5.5% vs. 48.0% ± 6.1%, P > 0.05). There were also no significant differences for the remainder soft-tissue activities and the urinary excretion rates before and after therapy. Similar results were obtained in rabbits treated with 186Re-HEDP: Bone uptake (44.8% ± 6.7% vs. 40.4% ± 4.9%, P > 0.05) and urinary excretion revealed no significant differences before and after treatment. Conclusion: No significant impairment of bone uptake of 99mTc-HDP could be observed 8 wk after high-dose radionuclide bone therapy. Because both the biokinetic data obtained for 186Re-HEDP and 153Sm-EDTMP and the myelotoxic effects were quite similar in rabbits to those in patients, it seems justifiable to expect the same result (i.e., no significant alteration of bone uptake of radiolabeled bisphosphonates) in patients undergoing a second radionuclide therapy within 2–3 mo after standard treatment with 186Re-HEDP or 153Sm-EDTMP.

Key Words: 99mTc-hydroxymethylene diphosphonate • 186Re-(tin)1,1-hydroxyethylidene diphosphonate • 153Sm-ethylenediaminetetramethylenephosphonate • bone uptake • post-therapeutic alterations


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Treatment with 186Re-(tin)1,1-hydroxyethylidene diphosphonate (HEDP) or 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) for pain has been proven safe and successful in patients with widespread osseous metastases (1–6). Because the duration of pain relief is limited to a mean of 2–3 mo, subsequent therapy is recommended as long as blood cell counts, that is, leukocyte and platelet counts, are in the normal range. A drop in the level of platelets and leukocytes in the peripheral blood—the major side-effect of that treatment modality—is caused by irradiation of stem cells in the bone marrow by the ß-particles of the skeleton-bound radiopharmaceutical (3,7). Thereby, it is known that higher activities of the radiopharmaceutical go along not only with higher grades of myelotoxicity but also with higher success rates for pain improvement (4,8). Consequently, skeletal uptake of administered activity is a main determinant of both radiation damage to bone marrow and the success of radionuclide therapy for bone pain. However, no data have been available on the skeletal uptake of radiolabeled bisphosphonates administered 2–3 mo after radionuclide bone therapy. The aim of this animal study, therefore, was to calculate bone uptake of 99mTc-hydroxymethylene diphosphonate (HDP) before and 8 wk after high-dose treatment with 153Sm-EDTMP or 186Re-HEDP to test whether bone uptake was impaired after therapy. We used a recently introduced method based on 3-phase bone scanning to quantify skeletal uptake of radiolabeled bisphosphonates (9,10).


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Animals and Study Design
Studies were performed on 12 female New Zealand White rabbits, 10–12 wk old and weighing a mean (±SD) of 2.5 ± 0.2 kg (Charles River, Kissleg, Germany). They were sufficiently large to undergo scintigraphic bone uptake measurements. For radionuclide bone therapy, we used 186Re-HEDP (Mallinckrodt, Petten, The Netherlands) (n = 6) and 153Sm-EDTMP (CIS, Gif-Sur-Yvette, France) (n = 6). Both tracers were administered intravenously at a standard activity of 400 MBq per kilogram of body weight. This dose has been proven myelotoxic in rabbits. It induces, in the platelet and leukocyte counts of their peripheral blood, a drop comparable to that in patients treated with standard activities as described recently (11). The main reason that higher activities are needed in rabbits than in patients is that, in rabbits, the bones are much smaller and the bone marrow much less, compared with the range of the ß-particles. The result is lower irradiation of the bone marrow in rabbits than in patients, in whom a higher proportion of the ß-rays is deposited in the bone marrow.

All animal studies were approved by the Ministerium für Umwelt, Natur und Forsten des Landes Schleswig-Holstein (X 252-72241.121-17 56-8/98) according to the German Law of the Protection of Animals.

One week before and 8 wk after radionuclide treatment, quantitative bone scanning was performed as described below after administration of 100 MBq of 99mTc-HDP (Mallinckrodt, Petten, The Netherlands). Furthermore, quantitative scanning was also performed after application of 186Re-HEDP and 153Sm-EDTMP to calculate the skeletal uptake of the respective radiopharmaceutical.

Scintigraphic Skeletal Uptake Measurement
Whole-body images were acquired simultaneously from anterior and posterior views at 3 min, 3 h, and 24 h after a bolus injection of the respective radiopharmaceutical (99mTc-HDP, 186Re-HEDP, or 153Sm-EDTMP). The acquisition time was 1 min in the blood-pool phase and 10 min for the later images. For each rabbit, images were obtained under the same conditions using a double-head gamma camera (Bodyscan; Siemens, Erlangen, Germany) equipped with high-resolution collimators for low energy. The energy windows were 140 keV ± 15%, 137 keV ± 15%, and 103 keV ± 15% for 99mTc, 186Re, and 153Sm, respectively.

For each image, the activities of the whole body, the urinary bladder, and the soft tissue of the flank were measured by region-of-interest (ROI) technique from both anterior and posterior views. Additionally, for uptake measurements of 186Re-HEDP or 153Sm-EDTMP, a rectangular ROI adjacent to the body was used to measure the bremsstrahlung of the ß-particles of the radionuclide. An example of ROI positions is given in Figure 1. From these data, the geometric mean for each ROI was calculated after correction for different acquisition times; for radioactive decay; and, in cases of 186Re-HEDP or 153Sm-EDTMP, for bremsstrahlung. The initial whole-body activity of each rabbit was used as the reference value for further calculations of activity data, which are given as a percentage of initial whole-body activity. According to a simplified 3-compartment model, soft-tissue activity as compared with initial whole-body activity equals the activity of the flank as compared with the initial flank activity at 3 min after injection. Urinary excretion was determined by the difference of whole-body activities between the reference image at 3 min and the image of interest plus urinary bladder activity. From these data, bone uptake was calculated for 24 h after injection as 100% of initial whole-body activity minus both urinary excretion and soft-tissue retention as described in detail elsewhere (9,10).



View larger version (60K):
[in this window]
[in a new window]
  		FIGURE 1. ROI positions on posterior whole-body scintigram of rabbit 3 h after injection of 1,000 MBq of 186Re-HEDP.

 
Statistical Analysis
Data are given as mean ± 1 SD. A 2-tailed Student t test for unpaired data (including both the test of David, Pearson, and Stephens to prove normal distribution of the data and the F test) was used to evaluate statistical differences between rabbit subgroups, with P < 0.05 considered statistically significant (12).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 CONCLUSION
 REFERENCES
 
The mean bone uptake of 99mTc-HDP at 24 h after injection before treatment with 153Sm-EDTMP was 51.1% ± 5.5% of initial whole-body activity. Eight weeks after radionuclide therapy, the mean bone uptake value, 48.0% ± 6.1%, showed no significant difference (P > 0.05) from the pretreatment result (Table 1). Also, no significant differences between before- and after-therapy values could be proven for the remainder soft-tissue activities (16.4% ± 5.3% vs. 17.8% ± 3.5%) or for the urinary excretion rates at 24 h after injection (31.6% ± 3.0% vs. 34.2% ± 4.7%).


View this table:
[in this window]
[in a new window]
  		TABLE 1 Bone Uptake, Soft-Tissue Retention, and Urinary Excretion of 99mTc-HDP in 6 Rabbits at 24 Hours After Injection Before and After Treatment with 1,000 MBq 153Sm-EDTMP

 
Similar results were obtained in rabbits treated with 186Re-HEDP (Table 2). Both the mean bone uptake of 99mTc-HDP (44.8% ± 6.7% vs. 40.4% ± 4.9%) and the urinary excretion of 99mTc-HDP (37.0% ± 6.1% vs. 37.7% ± 4.9%) revealed no significant differences (P > 0.05 each) before and after treatment, although bone uptake values were lower in all animals after therapy. The remainder soft-tissue activity was significantly higher (P < 0.01) after radionuclide therapy (22.0% ± 0.4%) than before (17.7% ± 1.6%).


View this table:
[in this window]
[in a new window]
  		TABLE 2 Bone Uptake, Soft-Tissue Retention, and Urinary Excretion of 99mTc-HDP in 6 Rabbits at 24 Hours After Injection Before and After Treatment with 1,000 MBq 186Re-HEDP

 
Between the 2 rabbit groups treated with either 153Sm-EDTMP or 186Re-HEDP, no significant differences (P > 0.05 each) could be proven for the mean bone uptake, soft-tissue retention, and urinary excretion of 99mTc-HDP (Tables 1 and 2).

The mean bone uptake, soft-tissue retention, and urinary excretion of 153Sm-EDTMP at 24 h after injection were 44.0% ± 6.5%, 9.8% ± 4.4%, and 46.3% ± 7.5%, respectively (Table 3). The corresponding results for 186Re-HEDP were 31.2% ± 1.5%, 16.2% ± 2.7%, and 52.6% ± 3.4%. Thus, a significantly higher bone uptake was found for 153Sm-EDTMP (P < 0.001), whereas soft-tissue retention was significantly lower for 153Sm-EDTMP (P < 0.02). No differences were found between the urinary excretion rates for 186Re-HEDP and 153Sm-EDTMP (P > 0.05).


View this table:
[in this window]
[in a new window]
  		TABLE 3 Bone Uptake, Soft-Tissue Retention, and Urinary Excretion of 153Sm-EDTMP and 186Re-HEDP in Rabbits at 24 Hours After Injection

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
CONCLUSION
 REFERENCES
 
Because bone pain is relieved for only 2–3 mo in most patients undergoing radionuclide therapy with 186Re-HEDP or 153Sm-EDTMP, subsequent therapy is recommended as long as blood cell counts are in the normal range. The activity administered and the extent of radiopharmaceutical uptake by bone are known determinants of the success of this treatment (4,8,13). Radiation doses of up to 3 Gy to bone and bone marrow and of up to 140 Gy to metastatic sites have been reported (3,7,8,14,15), strongly suggesting at least alterations of the local bone metabolism and, thus, uptake of radiolabeled bisphosphonates by bone. For example, reduced bone uptake of radiolabeled bisphosphonates can be observed within the irradiation fields after external radiotherapy (16) that applies center doses of up to 40 Gy. Although comparably high local doses are achieved by radionuclide therapy only in single metastases and not in larger bone areas, most of the skeleton-bound activity of 186Re-HEDP and 153Sm-EDTMP, that is, 20%–50% of the total activity administered (10), is absorbed by nonmetastatic bone tissue. In contrast, in vitro experiments with rat osteoblastlike cells showed inhibitory effects at doses of as low as 100 cGy (17). Similar results, such as a dose-dependent decrease in cellular differentiation and proliferation and a decrease in the production of transforming growth factor ß1 and vascular endothelial growth factor as markers for radiation-induced cytokine profile alterations, were found by Dudziak et al. (18) for dose levels of 40, 400, and 800 cGy. Thus, even the lower irradiation of the bones may have a general effect on bone metabolism and on bone uptake of bisphosphonates. Therefore, it seems important to know about changes in bone uptake some 2–3 mo after radionuclide therapy.

In this animal study, skeletal uptake of 99mTc-HDP was measured as an indicator of bone metabolism before and 8 wk after high-dose treatment with 153Sm-EDTMP or 186Re-HEDP to assess any post-therapeutic impairment of bone uptake. To measure skeletal uptake of the radiolabeled bisphosphonates used in this study, we used a recently introduced method that has been proven valid in patients in comparison with data from literature (9,10). This method is based on scintigraphic 3-phase whole-body imaging in combination with conventional ROI technique and allows calculation of kinetic data for the compartments assumed in this model: bone, soft tissue, and urinary excretion.

Significant alterations of 99mTc-HDP uptake by bone 8 wk after radionuclide therapy with 153Sm-EDTMP or 186Re-HEDP could be excluded in this study. In animals that received 153Sm-EDTMP, uptake by bone was somewhat lower after radionuclide therapy in 4 of 6 rabbits, whereas in all animals treated with 186Re-HEDP, uptake was lower, although not significantly so. On account of follow-up studies in nonmetastatic-tumor patients undergoing repeated bone scintigraphy, we know that variations of up to ±10% in bone uptake are observed within 6 mo in many cases (W. Brenner et al., unpublished data, 2000). These variations are due mainly to the error in measurement of this method rather than to real changes in bone uptake. In this study, in 4 of 6 rabbits treated with 186Re-HEDP and in 1 of 6 rabbits treated with 153Sm-EDTMP, bone uptake values were more than 10% lower after radionuclide therapy, whereas in only 1 of these cases was bone uptake reduced by more than 20%. According to a potential error of measurement of about 10%, these differences were statistically not significant, nor do changes within this range seem crucial from the clinical point of view. Furthermore, these findings have been observed after high-dose treatment, that is, 400 MBq of either 153Sm-EDTMP or 186Re-HEDP per kilogram of body weight: The activities usually applied in patients are 37 and 15–20 MBq per kilogram of body weight for 153Sm-EDTMP and 186Re-HEDP, respectively. Thus, a significant impairment of bone uptake of radiolabeled bisphosphonates in patients undergoing a second radionuclide therapy within 2–3 mo after standard treatment with 153Sm-EDTMP or 186Re-HEDP is not to be expected according to the data provided in this study. Also, no significant changes in urinary excretion and soft-tissue retention of 99mTc-HDP could be observed after administration of 153Sm-EDTMP. Only the remainder soft-tissue activity of 99mTc-HDP was statistically increased after therapy with 186Re-HEDP; urinary excretion rate remained unchanged. High-dose treatment with 186Re-HEDP and 153Sm-EDTMP therefore did not significantly alter the biodistribution of radiolabeled bisphosphonates, suggesting no major impairment of bone uptake in general because of this therapeutic modality.

To justify the transfer of such a conclusion to patients, it seems necessary to check the validity of the animal model for both 153Sm-EDTMP and 186Re-HEDP. At 24 h after injection, kinetic data similar to those reported in patients undergoing radionuclide bone therapy were observed (5,8,10,19,20). The bone uptake values in patients at 24 h after injection were 47.7% ± 11.2% for 153Sm-EDTMP, soft-tissue retention was 12.7% ± 4.7%, and the urinary excretion rate was 39.5% ± 13.8% (10). The corresponding data in rabbits—44.0% ± 6.5% for bone uptake, 9.8% ± 4.4% for remainder soft-tissue activity, and 46.3% ± 7.5% for urinary excretion—showed no significant differences. Similar results were obtained for 186Re-HEDP, although bone uptake values in rabbits, at 31.2% ± 1.5%, were somewhat higher than the 21.8% ± 9.0% observed in patients. Nevertheless, the bone uptake values in rabbits were significantly higher for 153Sm-EDTMP than for 186Re-HEDP, clearly reflecting the same differences between the biodistribution pattern of these radiopharmaceuticals as already observed in patients (10). One point to be addressed, however, is the problem of a solely local change and reduction of bone uptake in metastases or the adjacent bone tissue, which may significantly hamper local-pain palliation in cases of retreatment. Because this point cannot be investigated by the model used in this study, a model with bone tumors or bone metastases is mandatory for further studies. For investigating the general effects of radionuclide bone therapy on bone uptake of bisphosphonates, however, the model used in this study—a normal nontumor model with animals large enough for scintigraphic bone scanning—seemed sufficient despite its limitations.

Furthermore, we could prove a transient decrease of about 50% and 60% in the leukocyte counts and platelet counts, respectively, of rabbits within 3 wk after radionuclide treatment. These findings are in line with the radiation-induced myelotoxic effects reported for patients treated with the activities recommended for clinical practice (4,21–23). Thus, the findings in rabbits concerning both the bone uptake and the biodistribution of 186Re-HEDP and 153Sm-EDTMP, as well as the radiation-induced myelotoxic effects, are comparable to the findings in patients. Therefore, one seems justified in expecting the same, that is, nonsignificant, effects on bone uptake in patients undergoing radionuclide therapy as are observed in rabbits.


   CONCLUSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
REFERENCES
 
In this study investigating the impact of radionuclide therapy with 186Re-HEDP and 153Sm-EDTMP on bone uptake of radiolabeled bisphosphonates in rabbits, no significant alterations of the bone uptake of 99mTc-HDP could be observed 8 wk after high-dose treatment. Because the biokinetic data obtained for 186Re-HEDP and 153Sm-EDTMP and the myelotoxic effects in rabbits were similar to those in patients, it seems justified to expect the same results on bone uptake in patients as in rabbits. Thus, significant impairment of the bone uptake of radiolabeled bisphosphonates in patients undergoing a second radionuclide therapy within 2–3 mo after standard treatment with 186Re-HEDP or 153Sm-EDTMP is not to be expected according to the data obtained from this animal study.


   ACKNOWLEDGMENTS
 
The authors thank Dr. Hans-Ulrich Wottge and his team for providing perfect animal care service. The authors are grateful for financial support from Mallinckrodt GmbH, Hennef, Germany.


   FOOTNOTES
 
Received Aug. 20, 2001; revision accepted Sep. 24, 2002.

For correspondence or reprints contact: Winfried Brenner, MD, Division of Nuclear Medicine, University of Washington Medical Center, 1959 NE Pacific St., Box 356113, Seattle, WA 98195-6113.

E-mail: winbren_2000{at}yahoo.com


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 

  1. Maxon HR, Schroder LE, Thomas SR, et al. Rhenium-186(Sn)HEDP for treatment of painful osseous metastases: initial clinical experience in 20 patients with hormone-resistant prostate cancer. Radiology. 1990;176:155–159.[Abstract/Free Full Text]
  2. Maxon HR, Schroder LE, Hertzberg VS, et al. Rhenium-186(Sn)HEDP for treatment of painful osseous metastases: results of a double-blind crossover comparison with placebo. J Nucl Med. 1991;32:1877–1881.[Abstract/Free Full Text]
  3. Graham MC, Scher HI, Liu GB, et al. Rhenium-186-labeled hydroxyethylene diphosphonate dosimetry and dosing guidelines for the palliation of skeletal metastases from androgen-independent prostate cancer. Clin Cancer Res. 1999;5:1307–1318.[Abstract/Free Full Text]
  4. Resche I, Chatal JF, Pecking A, et al. A dose-controlled study of Sm-153-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases. Eur J Cancer. 1997;33:1583–1591.
  5. Serafini AN, Houston SJ, Resche I, et al. Palliation of pain associated with metastatic bone cancer using Sm-153 lexidronam: a double-blind placebo-controlled clinical trial. J Clin Oncol. 1998;16:1574–1581.[Abstract/Free Full Text]
  6. Tian J, Zhang J, Hou Q, et al. Multicenter trial on the efficacy and toxicity of single-dose samarium-153-ethylene diamine tetramethylene phosphonate as a palliative treatment for painful skeletal metastases in China. Eur J Nucl Med. 1999;26:2–7.[Medline]
  7. Bayouth JE, Macey DJ, Kasi LP, Fossella FV. Dosimetry and toxicity of Sm-153-EDTMP administered for bone pain due to skeletal metastases. J Nucl Med. 1994;35:63–69.[Abstract/Free Full Text]
  8. Eary JF, Collins C, Stabin M, et al. Samarium-153-EDTMP biodistribution and dosimetry estimation. J Nucl Med. 1993;34:1031–1036.[Abstract/Free Full Text]
  9. Brenner W, Bohuslavizki KH, Sieweke N, Tinnemeyer S, Clausen M, Henze E. Quantification of diphosphonate uptake based on conventional bone scanning. Eur J Nucl Med. 1997;24:1284–1290.[Medline]
  10. Brenner W, Kampen WU, Kampen AM, Henze E. Skeletal uptake and soft tissue retention of Re-186-HEDP and Sm-153-EDTMP in patients with metastatic bone disease. J Nucl Med. 2001;42:230–236.[Abstract/Free Full Text]
  11. Brenner W, Brümmer C, von Forstner C, Kampen WU, Zuhayra M, Henze E. Myeloprotective potential of amifostine in rabbits undergoing high-dose treatment with Sm-153-EDTMP or Re-186-HEDP [abstract]. Eur J Nucl Med. 2000;27:1124.
  12. Sachs L. Applied Statistics: A Handbook of Techniques. Berlin, Germany: Springer; 1997:351–372.
  13. Collins C, Eary JF, Donaldson G, et al. Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: a phase I/II trial. J Nucl Med. 1993;34:1839–1844.[Abstract/Free Full Text]
  14. Rensburg AJ, Alberts AS, Louw WKA. Quantifying the radiation dosage to individual skeletal lesions treated with samarium-153-EDTMP. J Nucl Med. 1998;39:2110–2115.[Abstract/Free Full Text]
  15. Logan KW, Volkert WA, Holmes RA. Radiation dose calculations in persons receiving injection of samarium-153 EDTMP. J Nucl Med. 1987;28:505–509.[Abstract/Free Full Text]
  16. Fogelman I, Collier BD. An Atlas of Planar and SPECT Bone Scans. Köln, Germany: Deutscher Ärzte-Verlag, 1989:123–124.
  17. Zeng R, Wang J, Yang G. The effects of insulin-like growth factor-II on the proliferation of osteoblast-like cells in vitro. Zhonghua Kou Qiang Yi Xue Za Zhi. 2002;37:58–61.
  18. Dudziak ME, Saadeh PB, Mehrara BJ, et al. The effects of ionizing radiation on osteoblast-like cells in vitro. Plast Reconstr Surg. 2000;106:1049–1061.[Medline]
  19. de Klerk JMH, van Dijk A, van het Schip AD, Zonnenberg BA, van Rijk PP. Pharmacokinetics of rhenium-186 after administration of rhenium-186-HEDP to patients with bone metastases. J Nucl Med. 1992;33:646–651.[Abstract/Free Full Text]
  20. Farhanghi M, Holmes RA, Volkert WA, Logan KW, Singh A. Samarium-153-EDTMP: pharmacokinetic, toxicity and pain response using an escalating dose schedule in treatment of metastatic bone cancer. J Nucl Med. 1992;33:1451–1458.[Abstract/Free Full Text]
  21. Liepe K, Franke WG, Kropp J, Koch R, Runge R, Hliscs R. Comparison of rhenium-188, rhenium-186-HEDP and strontium-89 in palliation of painful bone metastases. Nuklearmedizin. 2000;39:146–151.[Medline]
  22. Sciuto R, Tofani A, Festa A, Giannarelli D, Pasqualoni R, Maini CL. Short- and long-term effects of 186Re-1,1-hydroxyethylidene diphosphonate in the treatment of painful bone metastases. J Nucl Med. 2000;41:647–654.[Abstract/Free Full Text]
  23. Kolesnikov-Gauthier H, Carpentier P, Depreux P, Vennin P, Caty A, Sulman C. Evaluation of toxicity and efficacy of Re-186-hydroxyethylidene diphosphonate in patients with painful bone metastases of prostate or breast cancer. J Nucl Med. 2000;41:1689–1694.[Abstract/Free Full Text]




This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brenner, W.
Right arrow Articles by Henze, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brenner, W.
Right arrow Articles by Henze, E.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH RSS TABLE OF CONTENTS
JOURNAL OF NUCLEAR MEDICINE TECHNOLOGY THE JOURNAL OF NUCLEAR MEDICINE