Testis dosimetry in individual patients by combining a small-scale dosimetry model and pharmacokinetic modeling-application of¹¹¹In-Ibritumomab Tiuxetan (Zevalin^®)

Abstract

A heterogeneous distribution of radionuclides emitting low-energy electrons in the testicles may result in a significant difference between an absorbed dose to the radiosensitive spermatogonia and the mean absorbed dose to the whole testis. This study focused on absorbed dose distribution in patients at a finer scale than normally available in clinical dosimetry, which was accomplished by combining a small-scale dosimetry model with patient pharmacokinetic data. The activity in the testes was measured and blood sampling was performed for patients that underwent pre-therapy imaging with 111 In-Zevalin ® . Using compartment modeling, testicular activity was separated into two components: vascular and extravascular. The uncertainty of absorbed dose due to geometry variations between testicles was explored by an assumed activity micro-distribution and by varying the radius of the interstitial tubule. Results showed that the absorbed dose to germ cells might be strongly dependent on the location of the radioactive source, and may exceed the absorbed dose to the whole testis by as much as a factor of two. Small-scale dosimetry combined with compartmental analysis of clinical data proved useful for gauging tissue dosimetry and interpreting how intrinsic geometric variation influences the absorbed dose.

The Relevance of Dosimetry in Precision Medicine

“…This closure could potentially serve as a bridge between organ and tissue dosimetry and in the interpretation of intrinsic geometric variation and its uncertainties in absorbed dose. An example of this approach in a pretherapy clinical study with 111 In-ibritumomab tiuxetan was given by Meerkhan et al (62). The authors focused on the dosimetry for the testicle and presented significant differences in the absorbed dose to the radiosensitive germ cells depending on the location of the radioactive source region and geometry variations of the seminiferous tubule (62).…”

“…An example of this approach in a pretherapy clinical study with 111 In-ibritumomab tiuxetan was given by Meerkhan et al (62). The authors focused on the dosimetry for the testicle and presented significant differences in the absorbed dose to the radiosensitive germ cells depending on the location of the radioactive source region and geometry variations of the seminiferous tubule (62). Further research is needed in this area for establishing dose-response relationships.…”

Quantitative γ-H2AX immunofluorescence method for DNA double-strand break analysis in testis and liver after intravenous administration of 111InCl3

“…Concerning absorbed dose-effect relationships of radiopharmaceuticals, it is conventionally assumed that a radiopharmaceutical is homogeneously distributed within the source region, giving a uniform deposition of the radiation energy within the target region. However, it is known that the absorbed dose to individual cells depends on the microscopic distribution of the radioactivity [40][41][42][43]. Thus, a recurring important question in internal radiation dosimetry research is the link between the quantity of the absorbed dose and certain biological effects in the volume of energy deposition.…”