**4. General overview and final remarks**

18 Will-be-set-by-IN-TECH

of primary showers and therefore obtaining straightforwardly the corresponding absolute dose distribution. This information will be necessary for the calculation of radiobiological

The 3D absolute dose distribution constitutes the basic required information for implementing suitable algorithms devoted to estimate the TCP and NTCP. As mentioned previously, the linear quadratic model has been implemented for TCP estimation. As example of how to proceed, it has been arbitrary taken a total infused activity of 1mCi and typical values for the LQ radiobiological parameters have been used according to the literature, namely *α* = 0.12*Gy*−<sup>1</sup> and *β* = 0.0137*Gy*−<sup>2</sup> given a relationship of *α*/*β* = 8.7591. Figure 19 reports the

Fig. 19. TCP for the slice of interest obtained for 1*mCi* activity delivered by 131I.

However, it is necessary to remark that in real clinical situations TCP and NTCP estimation will require the implementation of some mechanism dedicated to the identification of normal/tumor tissue regions in order to proceed with the assigment of the corresponding radiobiological parameters. Actually, TCP evaluations have to be applied to tumor region, whereas NTCP evaluations apply to normal organs, each having different radiobiological parameter values. Once the previous step is accomplished the calculation method is

Similarly, it can be proposed some model for calculating the NTCP. With the aim of highlighting the required procedure, typical radiobiological values for the LKB model have

Fig. 18. Relative dose distribution on virtual patient irradiated by 131I.

obtained TCP distribution for the slice of interest.

performed following the procedure described above.

quantities.

The adequacy of the developed radiation transport simulation code based on PENELOPE v.2008 for nuclear medicine and focused on beta-emitters dosimetry has been preliminary investigated checking the consistency of the results expected when considering electron transport in the energy range from 5*keV* to 5*MeV*.

In this sense, dose point kernels have been calculated for several monoenergetic and spectral sources including the most commonly used radionuclides for typical nuclear medicine therapies.

Contrary to other works, it was considered the *RCSDA* range for both monoenergetic and spectrum sources, instead of the *X*<sup>90</sup> parameter used commonly on spectrum sources. Therefore it could be not straightforward to compare the obtained results for radionuclides with those reported by other authors. However, it does not constitute a significant drawback because comparisons can be performed for monoenergetic emission sources, which may help for assessing the reliability and accuracy of the proposed method.

It is interesting to comment about the obtained results for sDPK when inserting inhomogeneities. It has been found that non negligible abrupt changes appear in sDPK curves poducing remarkable discontinuity on the sDPK derivate. This behaviour may make difficult or actually avoid adequate analytical calculation of sDPK, as could be the case of realistic clinical situations. In this sense, it constitutes one of the main advantages of developing and implementing MC methods devoted to reliable radiation transport computation.

Technical features of simulation process have been studied in detail including convergence of representative observable mean values and standard deviations. In view of the specific requirements for most of the calculation performed in this work, it has been found that 107 primary showers seems to be a convenient and suitable compromise between calculation time and accurate enough results.

Regarding the investigations about the separation and characerization of the different contributions to the total absorbed dose, it should be mentioned that the main contribution comes from primary radiation, as expected. Although clearly non negligible, scattering contributions are always significantly lower than the primary component to absorbed dose. In addition, it has been shown how to obtain the different dose contributions at different

Several application examples have been added considering typical clinical situations in order

Dosimetry for Beta-Emitter Radionuclides by Means of Monte Carlo Simulations 285

As result from the proposed method, it was possible to characterize the scaled dose point kernel, as an important parameter of common daily use in nuclear medicine practice. In addition, the computation of sDPK has been also used for taking advantage of preliminary assessment of reliability and accuracy of the performed dosimetric calculations with the

The developed simulation code adapted for nuclear medicine radiation transport and dose delivering has been successfully integrated and complemented with dedicated algorithms devoted to patient image reading and interpreting for both anatomical and metabolic patient-specific medical images. Therefore, as example of the potentiality of the developed calculation system, it was shown how to estimate realistic dose distributions computed over reliable patient-specific virtual phantoms using activity information from SPECT DICOM images and the geometries and materials obtained from CT DICOM images. Furthermore, dose volume histograms (DVH) as well radiobiological quantities, like TCP and NTCP can be straightforwardly determined once 3D absorbed dose is already calculated. In base on the obtained performance, it should be emphasized that, after further rigorous tests and benchmarkings, the proposed calculation system would be able to provide accurate and reliable information enough to suggest its consideration as a suitable and useful tool for

A. Sánchez-Crespo, P. & Larsson, S. (2004). Positron flight in human tissues and its influence

Bielajew, A. & Salvat, F. (2001). Improved electron transport mechanics in the penelope

D.J. Brenner, L.R. Hlatky, P. H. E. H. & Sachs, R. (1995). A convenient extension of the

E.B. Bolch, L.G. Bouchet, J. R. B. W. J. S. R. H. A. E. B. A. S. C. & Watson, E. (1999). Mird

G. Luxton, P. K. & King, C. (2008). A new formula for normal tissue complication probability

H. Yoriyaz, M. S. & dos Santos, A. (2001). Monte carlo mcnp-4b–based absorbed dose

*Beam Interactions with Materials and Atoms* Vol. 173(Issue 3): 332 – 343. Dale, R. (1988). Radiobiological assessment of permanent implants using tumour

*journal of radiation oncology, biology, physics* Vol. 32(No. 2): 379 – 390.

on pet image spatial resolution, *European Journal of Nuclear Medicine and Molecular*

monte-carlo model, *Nuclear Instruments and Methods in Physics Research Section B:*

repopulation factors in the linear-quadratic model, *British Journal of Radiology* Vol.

linear-quadratic model to include redistribution and reoxygenation, *International*

panphlet no. 17: The dosimetry of nonuniform activity distributions - radionuclide s values at the voxel level, *The Journal of Nuclear Medicine* Vol. 40(No. 1): 11S – 36S. F. Botta, A. Mairani, G. B. M. C. A. D. D. A. F. A. F. M. F. G. P. G. P. & Valente, M. (2011).

Calculation of electron and isotopes dose point kernels with fluka monte carlo code for dosimetry in nuclear medicine therapy, *Medical Physics* Vol. 38(No. 7): 3944 – 3954.

(ntcp) as a function of equivalent uniform dose (eud), *Physics in Medicine and Biology*

distribution estimates for patient-specific dosimetry, *The Journal of Nuclear Medicine*

to support the exposed concepts and procedures.

developed code.

**5. References**

routine dosimetric calculations.

*Imaging* Vol. 31(No. 1): 44 – 51.

62(No. 735): 241 – 244.

Vol. 53(No. 1): 23 – 36.

Vol. 42(No. 4): 662 – 669.

positions and therefore obtaining that relative importance of scattering component varies significantly according to the tally position. Furthermore, the relative balance between primary and scattering contributions has shown to be dependent upon the physical properties of specific considered material.

Nevertheless, in the case of monoenergetic sources it has been obtained that the relative greater importance of the scattering contribution occur at distances larger than the *RCSDA* and it could be inferred that the same may happen for radioisotopes.

It can been concluded that a characterization of primary and scattering contributions to the total absorbed demand significant efforts. However, the importance of investigating about this would be relevant for further radiobiological studies, because they can take advantage from the characterization of dose components for assessing improved results including LET-weighted dosimetry. When dealing with beta-minus emitters the relative impact of performing LET-weighted dosimetry could be somehow negiglibe becuase of the almost constant LET depence on electron kinetic energy within the range of clinical interest. However, on the other hand, implementing this kind of procedures could be really important for alpha-emitters dosimetry due to the involved high LET values and variations between energy fluence and particle type associated to primary and scattering components.

When considering different absorbing media, like lung or bone, it has been obtained that sDPK show qualitatively the same behaviour found for water. Therefore, it seems possible to propose that sDPK could be satisfactory assessed by analytical methods whenever considering homogeneous media. Furthermore, exhaustive analysis and investigations about the precedent results, which have not been discussed in this work, may suggest that simplified models based on linear scaling of stopping powers could provide acceptable conversion between different biological materials. This scenario may strongly improve calculation comfortability for analytical methods. However, it should be emphasized that MC methods would always provide more accurate and reliable results. Actually, MC methods should be strongly recommended when dealing with complex situations, as may be a realistic patient-specific dose distribution calculation.

In addition, it is important to remark that this MC direct simulation on patient images can be very useful and convenient in some selected cases, like the presence of inhomogeneities, whereas in case of homogeneous tissue simple methods due to their less demanding requirements (especially in terms of computation time) even providing results with accuracy more than adequate. In addition, poor image (anatomical or metabolic) resolution may strongly affect MC calculation, which may be taken as a possible drawback of the proposed method.

Significant improvements regarding CPU calculation time may be assessed in some situations appropriate for suitable approximations allowing deterministic computation, but it is out of the scopes of this work. Otherwise when dealing with homogeneous tissues, analytical methods will be more adequate than MC simulations, preserving MC techniques as the most reliable and recommendable method, at least up today, for accurate dosimetry in presence of inhomogeneities.

Summarizing, this work presented a suitable and useful description about the main features involved in the development and implementation of Monte Carlo techniques for nuclear medicine purposes. A general overview of nuclear medicine dosimetry and radiation transport concepts has been presented. In addition, simplified and detailed explanations have been provided about how to design and elaborate dedicated Monte Carlo subroutines for nuclear medicine purposes.

Several application examples have been added considering typical clinical situations in order to support the exposed concepts and procedures.

As result from the proposed method, it was possible to characterize the scaled dose point kernel, as an important parameter of common daily use in nuclear medicine practice. In addition, the computation of sDPK has been also used for taking advantage of preliminary assessment of reliability and accuracy of the performed dosimetric calculations with the developed code.

The developed simulation code adapted for nuclear medicine radiation transport and dose delivering has been successfully integrated and complemented with dedicated algorithms devoted to patient image reading and interpreting for both anatomical and metabolic patient-specific medical images. Therefore, as example of the potentiality of the developed calculation system, it was shown how to estimate realistic dose distributions computed over reliable patient-specific virtual phantoms using activity information from SPECT DICOM images and the geometries and materials obtained from CT DICOM images. Furthermore, dose volume histograms (DVH) as well radiobiological quantities, like TCP and NTCP can be straightforwardly determined once 3D absorbed dose is already calculated. In base on the obtained performance, it should be emphasized that, after further rigorous tests and benchmarkings, the proposed calculation system would be able to provide accurate and reliable information enough to suggest its consideration as a suitable and useful tool for routine dosimetric calculations.

#### **5. References**

20 Will-be-set-by-IN-TECH

positions and therefore obtaining that relative importance of scattering component varies significantly according to the tally position. Furthermore, the relative balance between primary and scattering contributions has shown to be dependent upon the physical properties

Nevertheless, in the case of monoenergetic sources it has been obtained that the relative greater importance of the scattering contribution occur at distances larger than the *RCSDA*

It can been concluded that a characterization of primary and scattering contributions to the total absorbed demand significant efforts. However, the importance of investigating about this would be relevant for further radiobiological studies, because they can take advantage from the characterization of dose components for assessing improved results including LET-weighted dosimetry. When dealing with beta-minus emitters the relative impact of performing LET-weighted dosimetry could be somehow negiglibe becuase of the almost constant LET depence on electron kinetic energy within the range of clinical interest. However, on the other hand, implementing this kind of procedures could be really important for alpha-emitters dosimetry due to the involved high LET values and variations between

When considering different absorbing media, like lung or bone, it has been obtained that sDPK show qualitatively the same behaviour found for water. Therefore, it seems possible to propose that sDPK could be satisfactory assessed by analytical methods whenever considering homogeneous media. Furthermore, exhaustive analysis and investigations about the precedent results, which have not been discussed in this work, may suggest that simplified models based on linear scaling of stopping powers could provide acceptable conversion between different biological materials. This scenario may strongly improve calculation comfortability for analytical methods. However, it should be emphasized that MC methods would always provide more accurate and reliable results. Actually, MC methods should be strongly recommended when dealing with complex situations, as may be a realistic

In addition, it is important to remark that this MC direct simulation on patient images can be very useful and convenient in some selected cases, like the presence of inhomogeneities, whereas in case of homogeneous tissue simple methods due to their less demanding requirements (especially in terms of computation time) even providing results with accuracy more than adequate. In addition, poor image (anatomical or metabolic) resolution may strongly affect MC calculation, which may be taken as a possible drawback of the proposed

Significant improvements regarding CPU calculation time may be assessed in some situations appropriate for suitable approximations allowing deterministic computation, but it is out of the scopes of this work. Otherwise when dealing with homogeneous tissues, analytical methods will be more adequate than MC simulations, preserving MC techniques as the most reliable and recommendable method, at least up today, for accurate dosimetry in presence of

Summarizing, this work presented a suitable and useful description about the main features involved in the development and implementation of Monte Carlo techniques for nuclear medicine purposes. A general overview of nuclear medicine dosimetry and radiation transport concepts has been presented. In addition, simplified and detailed explanations have been provided about how to design and elaborate dedicated Monte Carlo subroutines for

energy fluence and particle type associated to primary and scattering components.

and it could be inferred that the same may happen for radioisotopes.

of specific considered material.

patient-specific dose distribution calculation.

method.

inhomogeneities.

nuclear medicine purposes.


**1. Introductions** 

nuclear medicine techniques.

**12** 

*China* 

**Skeleton System** 

*Peking University First Hospital* 

Bone and soft tissue disease is kind of detrimental disease and the precise diagnosis and timely therapy is also the clinical doctors' object of a prolonged endeavour. This chapter will introduce the diagnostic and therapeutic methods of bone and soft tissue diseases with

The singular advantages of skeletal scintigraphy are high sensitivity in detecting early disease and its ability to survey the entire skeleton quickly and reasonable expense. Most broadly, the uptake of skeletal seeking radiotracers depicts osteoblastic activity and regional blood flow to bone. Any medical condition that changes either of these factors in a positive

Radionuclide distribution has played an important role in understanding normal bone metabolism, in addition to the metabolic effects of pathologic involvement. Radionuclide imaging of the skeleton is being used with increasing frequency in the evaluation of abnormalities involving bones and joints. Several studies have demonstrated that different information can be obtained by radionuclide bone imaging compared with radiography and blood chemistry analysis. Innovations in equipment design and other advances, such as single-photon emission computed tomography (SPECT), positron emission tomography (PET), positron emission tomography/computed tomography (PET/CT), positron emission tomography/magnetic resonance imaging (PET/MR) and hybrid SPECT/CT have been

The first part of this chapter introduces the mechanism of skeletal radionuclide imaging, which also reviews part knowledge of skeletal anatomy and physiology. The remainder of the chapter discusses radionuclide imaging of the bones and joints, with an emphasis on the applications of the imaging procedures, and the radionuclide therapy of some bone tumors.

Bone scintigraphy is one of the most common investigations performed in nuclear medicine and routinely used in the evaluation of patients with cancer for suspected bone metastases and in various benign musculoskeletal conditions. The uptake of radiotracers in bone is associated with local osteoblastic activity and regional blood flow. More radiopharmaceutical is delivered to hyperemic areas. Either increased blood flow or increased osteogenesis for many types of lesions results in higher tracer uptake than in

or negative way can result in an abnormal skeletal scintigram.

incorporated into the investigation of various musculoskeletal diseases.

**2. Mechanism and technique of skeletal radionuclide imaging** 

unaffected or normal parts of the skeleton.

Rongfu Wang

