JNM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH 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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wolfram, R. M.
Right arrow Articles by Sinzinger, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wolfram, R. M.
Right arrow Articles by Sinzinger, H.
Journal of Nuclear Medicine Vol. 43 No. 9 1254-1258
© 2002 by Society of Nuclear Medicine

Basic Science Investigations

Radioiodine Therapy Induces Dose-Dependent In Vivo Oxidation Injury: Evidence by Increased Isoprostane 8-Epi-PGF2{alpha}

Roswitha M. Wolfram, MD1, Alexandra C. Budinsky, MS2, Barbara Palumbo, MD3, Renato Palumbo, MD3 and Helmut Sinzinger, MD4,5

1 Department of Angiology, University of Vienna, Vienna, Austria
2 Clinical Division of Oncology, Department of Internal Medicine I, University of Vienna, Vienna, Austria
3 Institute of Nuclear Medicine, University of Perugia, Perugia, Italy
4 Department of Nuclear Medicine, University of Vienna, Vienna, Austria
5 Wilhelm Auerswald Atherosclerosis Research Group (ASF) Vienna, Vienna, Austria


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
131I is the treatment of choice for differentiated thyroid cancer and hyperthyroidism. A relationship between low-density lipoprotein oxidation and radioiodine therapy-related side effects, consequently inducing increased formation of 8-epi-prostaglandin F2{alpha} (PGF2{alpha}) in situ, has recently been reported by several investigators. Isoprostanes, among them 8-epi-PGF2{alpha}, have been associated with increased oxidation injury due to various pathologic conditions in vivo. The aim of this study was to investigate the possible induction of oxidative stress as a consequence of 131I therapy. Methods: 8-epi-PGF2{alpha} was examined in plasma, serum, and urine in 42 patients undergoing radioiodine treatment of hyperthyroidism or thyroid cancer. The 8-epi-PGF2{alpha} levels were analyzed daily for 1 wk and thereafter at different points up to 12 wk after treatment. Results: The isoprostane levels showed an increase after application of radioiodine in all investigated compartments. The effect was significantly higher and longer lasting after higher-activity therapy (2,960 or 7,400 MBq) than after lower-activity therapy (185 or 740 MBq). Conclusion: These findings document a significant, dose-dependent in vivo oxidation injury as a consequence of therapeutic radioiodine application to the salivary gland.

Key Words: radioiodine therapy • oxidation injury • isoprostanes • 8-epi-prostaglandin F2{alpha}


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
For certain types of hyperthyroidism and for remnants after total thyroidectomy in patients with differentiated thyroid cancer, 131I is the treatment of choice (1). Examination of lipoproteins after radioiodine therapy recently showed that low-density lipoprotein (LDL), temporarily, and high-density lipoprotein, later, are undergoing oxidative modification as a consequence of therapy (2). Oxidized LDLs in turn are known to be atherogenic (3), because they are rapidly taken up by monocytes or macrophages through pathways mediated by scavenger receptors (3). These pathways do not have a feedback control (4); thus, lipids may be taken up excessively. Consequently, the lipids are stored in macrophages, which are transformed into lipid-loaded foam cells (5). During LDL oxidation, the isoprostane 8-epi-prostaglandin F2{alpha} (PGF2{alpha}), among other isoprostanes, is generated in situ after free radical-mediated peroxidation of arachidonic acid (6). These isoprostanes are stable prostaglandinlike compounds and have been shown to be reliable markers of in vivo oxidation injury (7). Immunochemical and immunohistochemical studies revealed that both oxidized LDL and 8-epi-PGF2{alpha} are predominantly found along foam cells in the vascular wall (8,9). The aim of this study was to investigate whether therapeutic application of 131I leads to an alteration of isoprostane levels in plasma, serum, and urine, reflecting possible oxidation injury from this therapy.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Patients being treated with different activities of 131I (185, 740, 2,960, or 7,400 MBq) were examined during and after radioiodine therapy. Samples of blood and urine were collected in the morning on the day before therapy and daily thereafter until the 8th day, as well as after 2, 3, 4, 6, 8, 10, and 12 wk. Smokers were excluded because of their severely elevated levels of 8-epi-PGF2{alpha} (10,11). A total of 42 patients (18 men, 24 women) were investigated (Table 1).


View this table:
[in this window]
[in a new window]
  		TABLE 1 Patient Characteristics

 
Blood was drawn the morning after a fast of at least 12 h and was tested for levels of lipids, lipoproteins, thyroid-stimulating hormone, creatinine, and 8-epi-PGF2{alpha} and for safety parameters (glutamyltranspeptidase, glutamate-oxalacetate-transaminase, creatine kinase, glutamate-pyruvate-transaminase, and LDH). A 24-h urinary sample was collected at the same time, and after total urinary volume had been assessed, an aliquot was stored at -70°C.

Serum 8-Epi-PGF2{alpha}
Blood was drawn into glass vials, which were placed immediately into a water bath at 37°C for exactly 60 min. Serum was then removed after centrifugation (4°C, 1,000g, 10 min) and stored until determination (no longer than 2 wk at less than -70°C) (12). To evaluate oxidation injury in vivo, the most prostaglandinlike isoprostane compartment was chosen and 8-epi-PGF2{alpha} was determined by a specific immunoassay. To evaluate interassay variability, the respective sample was determined several times in several assays. Intraassay variability was evaluated by assaying the same sample several times during the same assay procedure. Interassay variability within the normal range amounted to 3.8% ± 1.2%, whereas intraassay variability was 1.9% ± 0.7% (normal range, 150–250 pg/mL, n = 17).

Plasma 8-Epi-PGF2{alpha}
Blood samples were anticoagulated with 2% ethylenediaminetetraacetic acid and 1 mg/mL (final blood volume) acetylsalicylic acid. Immediate centrifugation at 4°C to obtain plasma was done at 1,000g for 10 min. Plasma was removed and stored at less than -70°C for no longer than 2 wk before determination. Interassay variability within the normal range was 5.5% ± 1.7%, whereas intraassay variability was 2.5% ± 0.7% (normal value, <20 pg/mL, n = 11).

Urinary 8-Epi-PGF2{alpha}
Urine was collected over a period of 24 h. Aliquots (10 mL) were taken for extraction and adjusted to pH 4.0 with formic acid. The eluate was subjected to silicic acid chromatography and further eluted. This final eluate was dried, recovered in buffer, and assayed after dilution. Cross-reactivity of the antibody with prostaglandins was less than 2%. Values are given in picograms of 8-epi-PGF2{alpha}/mg creatinine. Interassay variability within the normal range was 6.4% ± 2.3%, whereas intraassay variability was 2.7% ± 0.8% (normal range, 150–250 pg/mg creatinine, n = 14).

8-Epi-PGF2{alpha}-Assay
8-epi-PGF2{alpha} was determined after extraction and purification by chromatography. In vitro artifactual formation of 8-epi-PGF2{alpha} (which eventually could easily be generated by in vitro autooxidation of arachidonic or other fatty acids) was excluded by comparison with immediate measurements showing no difference in the respective eicosanoid. Cross-reactivity of the antibody was 8.6% for 8-epi-PGF2{alpha}.

Statistical Analysis
Values are presented as mean ± SE; significance was determined using the Student t test; P < 0.05 was considered statistically significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 CONCLUSION
 REFERENCES
 
Plasma 8-Epi-PGF2{alpha}
In patients treated with 185 MBq, 8-epi-PGF2{alpha} increased continuously until reaching a significant maximum by days 3 and 4 after treatment and then dropped continuously until reaching pretherapeutic levels after 3 wk (Fig. 1). In patients treated with 740 MBq, a significant increase of 8-epi-PGF2{alpha} was found after day 2, reaching the highest levels on days 3 and 4. After 3 wk, the levels continuously decreased until reaching pretherapeutic levels. From day 2 until week 2, a significantly higher plasma 8-epi-PGF2{alpha} was observed, with the highest levels occurring on days 3–5. The 8-epi-PGF2{alpha} plasma levels on days 2, 3, 4, 5, 6, 7, and 8, as well as after 2 wk, were significantly higher in the 740-MBq treatment group than in the 185-MBq treatment group. In the 7,400-MBq treatment group, we found a significant increase of plasma 8-epi-PGF2{alpha} after day 2 until week 8, and this increase also reached a maximum on days 3 and 4. The levels of 8-epi-PGF2{alpha} on days 2, 3, 4, 5, 6, 7, and 8, as well as after weeks 2, 3, and 8, were significantly higher in the 7,400-MBq treatment group than in the 185-MBq treatment group.



View larger version (24K):
[in this window]
[in a new window]
  		FIGURE 1. Kinetic of plasma 8-epi-PGF2{alpha} after radioiodine therapy. Dose-dependent increase in 8-epi-PGF2{alpha} is seen, with maximum at days 3 and 4 after therapy. Decline seems also to be dose dependent. D = day; W = week.

 
Serum 8-Epi-PGF2{alpha}
In the 185-MBq treatment group, the levels increased until reaching a peak on days 3 and 4; the increase was not, however, statistically significant at any time, and the levels dropped to pretherapeutic values after 6 d (Fig. 2). After patients received a treatment activity of 740 MBq, their serum 8-epi-PGF2{alpha} increased significantly on days 1, 2, 3, 4, and 5; reached the highest levels on days 3 and 4; and dropped to pretherapeutic levels after 2 wk. No statistically significant difference in levels of serum 8-epi-PGF2{alpha} was found between the 740-MBq treatment group and the 185-MBq treatment group. After patients received an activity of 2,960 MBq, a significant increase of serum 8-epi-PGF2{alpha} was observed from day 2 until week 6, with maximum levels occurring on days 3 and 4. The levels of serum 8-epi-PGF2{alpha} on days 2, 3, 4, 5, 6, 7, and 8, and also after weeks 2, 3, 4, and 6, were significantly higher in the 2,960-MBq treatment group than in the 185-MBq treatment group. After patients received 7,400 MBq, we found significantly increased levels of plasma 8-epi-PGF2{alpha} from day 2 through the rest of the observation period, with the highest levels occurring on days 4 and 5. The serum levels of 8-epi-PGF2{alpha} after day 2 and until week 12 were significantly higher in the 7,400-MBq treatment group than in the 185-MBq treatment group.



View larger version (23K):
[in this window]
[in a new window]
  		FIGURE 2. Kinetic of serum 8-epi-PGF2{alpha} after radioiodine therapy. Dose-dependent increase in 8-epi-PGF2{alpha} is seen, with maximum at days 3 and 4 after therapy. Decline seems also to be dose dependent. D = day; W = week.

 
Urinary 8-Epi-PGF2{alpha}
In the 185-MBq treatment group, the urinary 8-epi-PGF2{alpha} levels increased until reaching a maximum on days 3 and 4 (Fig. 3). Afterward, the urinary 8-epi-PGF2{alpha} decreased continuously and reached pretherapeutic levels after day 6, but none of the measured levels was statistically significant. After patients received an activity of 740 MBq, a significant increase of urinary 8-epi-PGF2{alpha} levels was observed on days 3, 4, 5, 6, 7, and 8, with a maximum occurring on days 3 and 4. The urinary 8-epi-PGF2{alpha} levels decreased after day 4 and reached pretreatment levels after 3 wk. No statistically significant difference in levels was found between the 740-MBq treatment group and the 185-MBq treatment group. In the 2,960-MBq treatment group, a significant increase was observed after days 1, 2, 3, 4, 5, 6, 7, and 8, as well as after weeks 2, 3, and 4, with the highest levels of urinary 8-epi-PGF2{alpha} occurring on days 3 and 4. The urinary 8-epi-PGF2{alpha} levels were significantly higher in the 2,960-MBq treatment group than in the 185-MBq treatment group from day 2 through week 4. In the 7,400-MBq treatment group, we found a significant increase of urinary 8-epi-PGF2{alpha} levels from day 1 through week 12, with the highest levels occurring on days 3 and 4. We found significantly higher urinary 8-epi-PGF2{alpha} levels in the 7,400-MBq treatment group than in the 185-MBq treatment group on days 2, 3, 4, 5, 6, 7, and 8, as well as after weeks 2, 3, 4, and 6.



View larger version (24K):
[in this window]
[in a new window]
  		FIGURE 3. Kinetic of urinary 8-epi-PGF2{alpha} after radioiodine therapy. Dose-dependent increase in 8-epi-PGF2{alpha} is seen, with maximum at days 3 and 4 after therapy. Decline seems also to be dose dependent. D = day; W = week.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
CONCLUSION
 REFERENCES
 
8-epi-PGF2{alpha} belongs to a series of bioactive prostaglandin F2-like compounds that are generated in vivo by free radical and LDL particle-mediated, nonenzymatic peroxidation of arachidonic acid (13). 8-epi-PGF2{alpha} is mitogenic and a vasoconstrictor and displays a potential proaggregation effect on human platelets measured in plasma, serum, and urine. 8-epi-PGF2{alpha} has been shown to be a reliable marker for oxidation injury and to increase in association with cigarette smoking (14), hypercholesterolemia (12,15), diabetes (16,17), and advanced age. The potential role of 8-epi-PGF2{alpha} in radiation therapy and radioiodine therapy as a new, noninvasive method of assessing radiation injury has not been investigated so far. The increased levels of 8-epi-PGF2{alpha} in plasma, serum, and urine in patients undergoing radioiodine therapy reflect the oxidative and possible radiation injury in these patients. In our study, we could demonstrate a dose-dependent increase of 8-epi-PGF2{alpha} after radioiodine therapy. The isoprostane values showed a comparable behavior in all investigated compartments. Although in the 185-MBq group no statistically significant increase of 8-epi-PGF2{alpha} could be found, an administered activity of 740 MBq led to significantly elevated values, further increasing with administration of 2,960 MBq and 7,400 MBq. In the last 2 groups, significance was found not only in comparisons with pretherapeutic levels but also in comparisons with levels after administration of 185-MBq activities. Furthermore, serum and urinary 8-epi-PGF2{alpha} values showed a significant increase after treatment with an activity of 7,400 MBq, consequently dropping after a peak at days 4 and 5 and days 3 and 4, respectively, but not reaching pretherapeutic values after 12 wk of follow-up. The peak concentrations reached in plasma, serum, and urine are comparable with results obtained from recent studies investigating the increase of 8-epi-PGF2{alpha} in cigarette smokers (18) and hyperlipoproteinemia patients (12). The somewhat elevated values of 8-epi-PGF2{alpha} seen before therapy in patients receiving a high 131I dose may be due to the athyrotic stage and the associated hyperlipidemia in these patients, who had mean cholesterol values at the time of therapy of 308 ± 36 and 322 ± 39 mg/dL, respectively. Our results indicate that 131I therapy of the thyroid gland can induce oxidative stress in vivo and is not restricted to the area of administration but is detectable, in a dose-dependent manner, even in plasma, serum, and urine. These results further suggest that the increase of isoprostanes after radioiodine therapy is partially reversible at low activities. However, in patients receiving an 131I activity of as high as 7,400 MBq, the values did not decrease to pretherapeutic values throughout the 12-wk follow-up period (as is analogous to observations in former heavy smokers, whose isoprostane levels dropped significantly after smoking cessation but never reached the values of healthy nonsmokers (14)). Long-term observations are therefore necessary. Alterations in circulating isoprostanes have been found in a variety of diseases. Isoprostanes, with their proaggregation (19), proliferative vasoconstriction (12,20), and mitogenic action, may favor impairing actions on various tissues.

Isoprostanes are established as reliable biomarkers for evaluating the extent of oxidative stress in atherosclerosis-associated diseases, including concomitant risk factors and patterns such as chronic lung disease (21). Isoprostanes have been detected in various tissues and body fluids such as blood (22) and lymph vessels (20,23). Measurement of 8-epi-PGF2{alpha} levels in patients undergoing radioiodine therapy might reflect the extent of oxidative or, in this special case, radiation injury resulting from different forms of treatment, but further investigation is required.


   CONCLUSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
REFERENCES
 
The assessment of isoprostanes, especially 8-epi-PGF2{alpha} levels, in various tissues and body fluids represents a new minimally invasive technique to evaluate the extent of oxidation injury in vivo. This method might allow monitoring of various treatment effects and evaluation of the possible benefits of using antioxidant therapy as an adjuvant to conventional treatment for minimizing therapy-related side effects.


   ACKNOWLEDGMENTS
 
The valuable help of Eva Unger in preparing and typing the manuscript is gratefully acknowledged.


   FOOTNOTES
 
Received Oct. 30, 2001; revision accepted May 6, 2002.

For correspondence or reprints contact: Helmut Sinzinger, MD, Wilhelm Auerswald Atherosclerosis Research Group (ASF) Vienna, Nadlergasse 1, A-1090 Vienna, Austria.

E-mail: Helmut.Sinzinger{at}akh-wien.ac.at


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 

  1. Gimm O. Thyroid cancer. Cancer Lett. 2001;163:143–156.[Medline]
  2. Haba T, Sakai Y, Koizumi J, Miyamoto S, Mabuchi H, Takeda R. A case of heterozygous familial hypercholesterolemia associated with hyperthyroidism: effects of triiodothyronine on low-density lipoprotein receptor and cholesterol synthesis. Metabolism. 1983;32:1129–1132.[Medline]
  3. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801–809.[Medline]
  4. Henriksen T, Mahoney EM, Steinberg D. Enhanced macrophage degradation of biologically modified low-density lipoprotein. Arteriosclerosis. 1983;3:149–159.[Abstract/Free Full Text]
  5. Aqel NM, Ball RY, Waldmann H, Mitchinson MJ. Monocytic origin of foam cells in human atherosclerotic plaques. Atherosclerosis. 1984;53:265–271.[Medline]
  6. Gopaoul NK, Nourous-Zadeh J, Molect AI, Anggard EE. Formation of PGF2-isoprostanes during oxidative modification of low-density lipoprotein. Biochem Biophys Res Commun. 1994;200:338–343.[Medline]
  7. Morrow JD, Frei B, Longmire AW, et al. Increase in circulating products of lipid peroxidation (F2-isoprostanes) in smokers: smoking as a cause of oxidative damage. N Engl J Med. 1995;332:1198–1203.[Abstract/Free Full Text]
  8. Mehrabi MR, Ekmekcioglu F, Tatzber F, et al. The isoprostane 8-epi-PGF2{alpha} is accumulated in coronary arteries isolated from patients with coronary heart disease. Cardiovasc Res. 1999;43:492–499.[Medline]
  9. Pratico D, Luliona L, Spagnoli L, et al. Monocytes in human atherosclerotic plaque contain high levels of 8-epi-PGF2{alpha}: an index of oxidative stress in vivo [abstract]. Circulation. 1996;94(suppl 1):277.
  10. Chehne F, Oguogho A, Lupattelli G, Palumbo B, Sinzinger H. Effect of quitting and restarting cigarette smoking in patients with clinically manifested atherosclerosis. Prostaglandins Leukot Essent Fatty Acids. 2001;64:307–310.[Medline]
  11. Kromer BM, Tippins JP. Coronary artery constrictions by the isoprostane 8-epi-prostaglandins F2{alpha}. Br J Pharm. 1996;119:1276–1280.[Medline]
  12. Oguogho A, Mehrabi M, Sinzinger H. Increased plasma, serum and urinary 8-epi-prostaglandin F2{alpha} in heterozygous hypercholesterolemia. Wien Klin Wochenschr. 1999;111:113–118.[Medline]
  13. Morrow JD, Harris TM, Roberts LJ II. Noncyclooxygenase oxidative formation of a series of novel prostaglandins: analytical ramifications for measurements of eicosanoids. Anal Biochem. 1990;184:1–10.[Medline]
  14. Reilly M, Delanty N, Lawson JA, Fitzgerald GA. Modulation of oxidant stress in vivo in chronic cigarette smokers. Circulation. 1996;94:19–25.[Abstract/Free Full Text]
  15. Davi G, Alessandrini P, Mezzetti A, et al. In vivo formation of 8-epi-prostaglandin F2{alpha} is increased in hypercholesterolemia. Arterioscler Thromb Vasc Biol. 1997;17:3230–3235.[Abstract/Free Full Text]
  16. Davi G, Ciabattoni G, Consoli A, et al. In vivo formation of 8-iso-prostaglandin F2{alpha} and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation. Circulation. 1999;99:224–229.[Abstract/Free Full Text]
  17. Feillet-Coudray C, Rock E, Coudray C, et al. Lipid peroxidation and antioxidant status in experimental diabetes. Clin Chim Acta. 1999;284:31–43.[Medline]
  18. Pilz H, Oguogho A, Chehne F, Lupattelli G, Palumbo B, Sinzinger H. Quitting cigarette smoking results in a fast improvement of in-vivo oxidation injury (determined via plasma serum and urinary isoprostane). Thromb Res. 2002;99:209–221.
  19. Leitinger N, Blazek I, Sinzinger H. The influence of isoprostanes on ADP-induced platelet aggregation and cyclic AMP-generation in human platelets. Thromb Res. 1997;86:337–342.[Medline]
  20. Sinzinger H, Oguogho A, Kaliman J. Isoprostane 8-epi-prostaglandin-F2{alpha} is a potent contractor of human peripheral lymphatics. Lymphology. 1997;30:155–169.[Medline]
  21. Montuschi P, Collins JV, Ciabattoni G, et al. Exhaled 8-isoprostane as an in-vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am J Respir Crit Care Med. 2000;162:1175–1177.[Abstract/Free Full Text]
  22. Oguogho A, Karanikas G, Kritz H, Riehs G, Wagner O, Sinzinger H. 6-oxo-PGF1alpha and 8-epi-PGF2alpha in human atherosclerotic vascular tissue. Prostaglandins Leukot Essent Fatty Acids. 1999;60:129–234.[Medline]
  23. Oguogho A, Kaliman J, Sinzinger H. Levels of eicosanoids (6-oxo-PGF1alpha and 8-epi-PGF2alpha) in human and porcine lymphatics and lymph. Lymphology. 1998;31:186–189.[Medline]



This article has been cited by other articles:


Home page
 J. Clin. Endocrinol. Metab.Home page
A. Dardano, L. Ghiadoni, Y. Plantinga, N. Caraccio, A. Bemi, E. Duranti, S. Taddei, E. Ferrannini, A. Salvetti, and F. Monzani
Recombinant Human Thyrotropin Reduces Endothelium-Dependent Vasodilation in Patients Monitored for Differentiated Thyroid Carcinoma
J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 4175 - 4178.
[Abstract] [Full Text] [PDF]

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 HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wolfram, R. M.
Right arrow Articles by Sinzinger, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wolfram, R. M.
Right arrow Articles by Sinzinger, H.

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