Validation of an in-house developed therapeutic dosimetric software tool for the treatment of 177Lutetium-DOTATATE peptide receptor radionuclide therapy

Radionuclides are used for therapeutic procedures in nuclear medicine, this treatment has been termed radiopharmaceutical therapy, which differs from external beam radiation therapy, since it uses radiolabelled therapeutic pharmaceutical agents [1]. It is therefore important to perform valid quantification of radionuclide dose in organs and tissues. Internal dosimetry is essential to evaluate the risk and benefit of these nuclear medicine procedures. Computer programs are needed to measure the dose to organs and tissues. Nuclear medicine has benefitted from advances in computer software and this gain was at a rapid pace [2]. Dose quantification using personal computer software in nuclear medicine was first developed in the early 1990’s and was distributed to two thousand users worldwide [3]. Electronic dose calculations were formed by the Radiation Dose Assessment Resource (RADAR) group [4]. This data can be downloaded from the internet website www.doseinfo-radar.com. The MIRD committee of the United States Society of Nuclear Medicine developed the MIRD formulism which has gained acceptance in nuclear medicine [5,6,7]:

$$\overline(_,_)=\sum_\widetilde\left(_,_\right). S(_\leftarrow _)$$

(1)

where:

\(\overline D\;(r_T,T_D)\) is the mean absorbed dose in Gy,

à is the time-integrated activity (TIA) in Bq.s,

rTrepresents the target region,

rs represents the source organ,

and the 'S-value' which is the cumulated activity in the source organ in Gy/Bq.s

The formulism requires knowledge of the cumulated activities, which are numerical values obtained from quantified nuclear medicine images. The ‘S-value’ are Monte Carlo calculation estimates using anthropomorphic phantoms and are radionuclide specific. Fisher-Snyder [8, 9], developed the first anthropomorphic phantom of the human body through a combination of geometric shapes, spheres, cylinders, cones, etc. Cristy et al. [10], then developed a series of phantoms, which represented children and adults of both genders. Stabin et al. [11], developed the female phantom, at three stages of pregnancy and non-pregnant. Other models for organs and structures include the brain [12], eye [13], peritoneal cavity [13], prostate gland [11], bone [12], rectum [14] and tumours [15]. The specific absorbed fractions from the models were “electronically published” by Stabin et al. [16]. This software was written in basic programming language using Visual Basic from Microsoft Corporation, which was later migrated to Windows software [16].

To serve as quality check, a few studies have highlighted the need for development of in-house dosimetry software tools to validate results of commercially available ones [17,18,19,20,21]. An advantage of available dosimetry software packages is that they include image functionality or large databases for S-values. The disadvantage, however, is the exclusion of features for objective calculations of activity to administer, pertaining organ doses and its standard error [19]. Another disadvantage is that most software packages are only commercially available. Whether in-house or commercial, the demand for patient-specific dosimetry necessitates the development of computer software. While many studies have investigated therapeutic dosimetry using in-house or commercial software, comparison of these software is still an open issue. The importance of comparing software tools for accurate absorbed dose calculations are therefore not highlighted in current literature. Authors believe that software comparison studies will assist in predicting possible organ under dosage or over dosage for consequent therapy efficacy or radiation induced toxicity, respectively. Computed absorbed doses can play a role in the amount of activity injected and the actual activity distribution in the organ. The aim of our study was therefore to validate an in-house developed software tool Masterdose using a commercial software tool OLINDA/EXM 1.0 for targeted peptide receptor radionuclide 177Lu-DOTATATE therapy.1

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