The calculated average absorbed doses to the testis, assuming a mono-exponential elimination, was 20 mGy for animals 4 h P.I. and 0.1 Gy for animals 25 h P.I. If no sacrifice had been carried out, the total absorbed dose to the testis would have been 0.4 Gy, which is the median lethal dose (LD
50) for mice spermatogonia [
29]. The human testis is much more sensitive, where 0.15 Gy causes a pronounced depression of sperm counts (oligospermia), and temporary sterility (azoospermia) has been reported at 0.3 Gy [
25,
26]. However, no significant increase in the number of γ-H2AX foci were seen in the mice exposed to these absorbed doses. However, within the liver of the same mice, the absorbed doses gave rise to a significant increase in the number of γ-H2AX foci per nuclei, even though the absorbed doses to the liver, 0.5 Gy and 3.2 Gy for animals exposed for 4 h and 25 h, respectively, were small in comparison to the absorbed doses held accountable for irradiation effects within the human liver. If no sacrifice had been carried out, the total absorbed dose to the liver would have been 12 Gy, which still is far below the 30–35 Gy from which a 5% incidence of RILD has been observed within the human liver [
15,
37,
38].
In this study, because no complete biokinetic data was collected, the absorbed dose calculation accounted only for self-absorbed doses in the testis and the liver itself; it did not include any cross-dose component originating from activity in the surrounding tissue. For both the testis and the liver, the self-absorbed dose is considered a good estimate of the total absorbed dose. It is known that
111In is taken up within the tubuli of the testis, more specifically in the basal layer containing the spermatogonia, after systemic administration of
111InCl
3 [
16,
17,
33]. Absorbed doses from such a heterogeneous activity distribution can be accounted for using small-scale dosimetry models. For the human testis [
41], the self-absorbed dose from
111In to the layer of spermatogonia could be a factor of two higher than the corresponding average absorbed dose to the whole testis. In addition, since
111In is a radionuclide emitting low energy conversion electrons and Auger electrons with high linear energy transfer (LET), the cellular and subcellular distribution will affect the absorbed dose to the nuclei. Rao et al. have shown a likely intranuclear distribution of
111In radiopharmaceuticals within the testicular cells and shown that the subcellular decay sites of high LET Auger-electron emitters primarily determine their radiotoxicity [
31,
33]. An intranuclear localization of
111In, with decay sites close to the DNA, would further increase the absorbed dose to the DNA. Furthermore, within the liver, published studies [
52‐
54] have shown a heterogeneous radiopharmaceutical distribution after intravenous injections, where radiolabeled colloids such as metal–plasma protein complexes [
17,
20‐
22] tend to accumulate within the liver macrophages, i.e., Kupffer cells. According to a small-scale anatomical model of the human liver tissue for radiation dosimetry [
42], the locally absorbed dose close to the source of the activity (e.g., the Kupffer cells) would increase slightly (5–10%) for 10% of the hepatocytes, whereas the self-absorbed dose to the Kupffer cells themselves would be 25 times higher than the average absorbed dose. Hence, a non-uniform radionuclide distribution within the studied tissues is likely present, both on a cellular and on a subcellular level. This, in combination with the high LET from the Auger emissions from
111In, may result in a non-uniform absorbed dose distribution to the different cells within the tissues, which may affect the accuracy of our results.