Cross-fire doses from β-emitting radionuclides in targeted radiotherapy. A theoretical study based on experimentally measured tumor characteristics

Abstract

A mathematical model based upon histological findings of cell cluster distributions in primary breast cancers and lymph node metastases was developed. The model is unique because it accounts for tumor cell cluster formations within both primary tumors and metastases. The importance of inter-cell cluster cross-fire radiation dose for beta-emitting radionuclides of different energies was studied. The cell clusters were simulated as spheres with 15, 25 and 50 microm radii having a homogeneous radioactivity distribution. The self-dose as well as the dose distribution around the spheres was calculated for seven radionuclides, (90)Y, (188)Re, (32)P, (186)Re, (159)Gd, (131)I and (177)Lu using the GEANT4 Monte Carlo code. Generally, the self-dose was decreasing with increasing energy of the emitted beta particles. An exception was (188)Re which, compared to (32)P, had higher beta energy as well as higher self-dose. This was due to the higher emission of conversion and Auger electrons in the (188)Re-decay. When the cell clusters had a mean distance that was shorter than the maximum range of beta-particles, then the inter-cluster cross-fire radiation contributed significantly to the absorbed dose. Thus, high-energy beta-particles may, in spite of a low self-dose to single clusters, still be favorable to use due to the contribution of inter-cluster cross-fire radiation.

In Vitro comparison of 213Bi- and 177Lu-radiation for peptide receptor radionuclide therapy

“…Despite this we assumed that the cells were homogeneous distributed, as clustering of cells can still occur, leading to an increase of the absorbed dose caused by cross-fire effect of neighboring cells. This was often observed in studies using low energy β-particles such as 177 Lu [31]. Therefore, this might have resulted in an underestimation of the absorbed dose caused by 177 Lu in our calculations.…”

“…The maximum path length in tissue for α-particle is 50–100 μm and for β-particle is 1–10 mm. Absorbed dose by cross-fire contributed from 177 Lu after incubation with 177 Lu-DOTATATE can be neglected, since the maximum path length of 177 Lu in tissue is approximately 2000 μm [30], the dose caused from cross-fire effect of 177 Lu was less than 1x10 -12 Gy with a distance of the 1500 μm [31]. As for 213 Bi-DOTATATE, the maximum path length of 213 Bi is 80 μm and the distance between the cells was >1500 μm, an additional dose to the calculated absorbed dose caused by cross-fire effect was not taken into account.…”

The La antigen is over-expressed in lung cancer and is a selective dead cancer cell target for radioimmunotherapy using the La-specific antibody APOMAB®

“…The anti-tumour potency of mAbs can be improved by arming mAbs with radionuclides and cytotoxic drugs, creating the new therapeutic modalities of radioimmunotherapy (RIT) and antibody drug conjugates, respectively. Although armed mAbs usually target tumour cell-surface antigens, they can also elicit bystander killing of surrounding, antigen-negative tumour cells [5,6]. Successful β-emitting RIT has led to the approval of two agents for treating CD20-positive B-cell lymphomas, although RIT for non-haematological malignancies has been limited by heterogeneous antigen expression and radio-resistance among other factors reviewed by [7].…”

The Somatostatin Analog 188Re-P2045 Inhibits the Growth of AR42J Pancreatic Tumor Xenografts

“…Neuroendocrine tumors, of the pancreas, gut, and lung over-express SSTR (12,13) and for this reason Re-188-P2045 may be an effective therapy for this class of tumors. The studies herein describe proof of concept for Re-188-P2045 therapy in the AR42J rat pancreatic tumor-xenograft nude mouse.…”