Dosimetry

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Radioiodine administration has been based on three different approaches: empirical fixed activity, dose limited by safe upper limits of blood dosimetry, and quantitative absorbed tumor dosimetry.

Fixed activities of 1.1-3.7GBq for remnant ablation and 3.7-7.4GBq for therapy are based on experience. They are known to be safe and this is the most widely used system but insufficient 131I may be delivered to eradicate tumor [22]. To overcome this problem some centers administer up to 11.1GBq (300mCi) in patients with distant metastases [79]. This may be associated with greater toxicity and unnecessary whole-body radiation exposure.

Activities administered within a safe upper limit of blood dose is an alternative method. Radioiodine administration is limited by bone marrow reserve with excessive doses resulting in hematological depression. Benua et al. recommended a maximum upper limit of 2 Gy blood dose [81]. Serious hematological complications were more common when blood doses exceeded 2 Gy compared to administrations below these limits (28% versus 6%, respectively). A number of centers perform this routinely to assist safe 131I administration.

Quantitative tumor dosimetry is the third alternative [68]. The rationale is that tumors have different biological behavior in different individuals which merits 131I treatment on a calculated patient-specific basis (Figure 15.5). Measurement of the absorbed dose in tumor has several advantages. Firstly, overtreatment and overall radiation exposure is kept to a minimum; an absorbed dose can vary widely with fixed activities, from ineffective to excessive. Secondly, it is the best way to determine whether future 131I therapy will be effective, so that treatment can be optimized and unnecessary treatment avoided. The greatest advantage is that adequate doses can be calculated to give the highest probability that tumor will be successfully eradicated [21,22].

Since the early 1970s, many attempts have been made to calculate the radiation dose absorbed by thyroid remnants and metastatic deposits [24]. Three parameters must first be determined: the initial activity (Ao) in the target tissue, the effective half-life of the radioiodine (Te), and the mass of tissue (m). We use single photon emission computed tomography (SPECT) or positron emission tomography

Figure 15.5 Dose map displaying absorbed dose within shoulder metastases from a patient with differentiated thyroid cancer calculated from voxel-based quantitative dosimetry using RMDP (Radionuclide Multimodality Dosimetry Package).Isobars represent varying absorbed doses.

imaging to measure the volume (mass) of metabolically active thyroid tissue or tumor and, after iodine treatment, perform sequential quantitative scans from which activity-time curves can be produced. By fitting the data and extrapolating to the time of administration, the initial activity in the target tissue and the effective half-life of iodine are determined. Calculations are then performed using the medical internal radiation dosimetry (MIRD) formula: D (absorbed dose) = 0.16AoTe/m.

Preliminary analysis of 25 dosimetric studies in patients with metastatic lesions has shown a wide variation of 5 to 621 Gy in the radiation absorbed dose from a fixed administered 131I activity of 5.5GBq [82]. There was evidence of a dose-response relationship, clearly explaining the spectrum of clinical response. Unfortunately, MIRD calculations are based on several assumptions, in particular that radioactivity is uniformly distributed throughout tumor and that washout of 131I from these tissues is governed by a single exponential function. If these assumptions are inaccurate, errors will be introduced into dosimetry estimates. In addition, errors in each of the other parameters (percentage uptake, target activity, effective half-life, and organ mass) will contribute to a combined error of absorbed dose [83]. Given all the problems with dosimetry and the potential for large errors, it could be questioned whether trying to perform dose calculations is worthwhile. However, with current efforts to produce accurate sequential registered three-dimensional SPECT images and dose-volume histograms of therapy distributions, a greater level of accuracy should be achieved, eventually resulting in improved effectiveness of treatment [84-89].

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