VI Autologous Bone Marrow Transplantation.pdf - Blog Science ...

ies. 10
Longer blood half-lives have been observed for such antibodies, which will
lead to increased bone marrow toxicity in comparison to RIT with murine antibodies
labeled with similar activity. 11
The selective removal of radiolabel from
humanized immunoconjugate in normal tissues might be possible by the introduction
of a labile linker between the chelated-radioisotope and the immunoglobulin.
Enzymes present in normal tissues, but absent in tumor could cleave
the low molecular weight linker chelate isotope complex from the
radioimmunoconjugate. This would lead to rapid urinary elimination of radioactivity
from normal tissues without significantly decreasing radioactivity in
tumor. This principle was applied successfully in experimental animal models. 7
RADIOISOTOPE SELECTIONS
The most appropriate isotopes for RTF are listed in Table 1. For diagnostic
and targeting applications, gamma emitters with energies in the 100-200 KeV
range are optimal. For therapeutic purposes localized energy deposition is required.
Radionuclides with high energy beta emissions (> 1 MeV) are desirable
for clinically detectable human cancer, (i.e.tumor over 1 cm in diameter). For
smaller tumors lower energy beta emissions, alpha emissions, or Auger electrons
might be more suitable. Such patients will have clinically undetectable tumors,
obviating possibilities for tumor targeting and tumor dosimetry studies.
This decreases the interest in the application of RLT in an adjuvant setting, as RIT
requires further optimization, which can only be achieved in studies of patients
with measurable disease.
The half-life of the radioisotopes should be long enough to allow substantial
accumulation of radioimmunoconjugate in the tumor, i.e. > 24 hours for intact
immunoglobulins. Shorter half-lives of radioisotope are appropriate for diagnostic
radiolabeled immunoglobulin fragments. Isotopes with a long half-life (>5
days) will cause more normal tissue damage if they are not ehminated early and
decay in circulation and normal organs.
Rhenium-186 is a good example of an isotope with an acceptable half-life
(3.8 days) and acceptable emissions for diagnostic purposes (0.137 MeV gamma)
and therapeutic purposes (1.07 MeV beta). Yttrium 90 (t 1/2 2.7 days) has a more
powerful beta emission (2.3 MeV), but no scannable gamma emission. Indium
111 (t 1/2 2.8 days, gamma emissions 0.173 - 0.247 MeV) has been utilized in low
activity prior to Yttrium injections in an effort to predict the behavior of the Yttrium
labeled immunoconjugate. This can only be of value if the biodistribution
and pharmacokinetics of the immunoconjugate are independent of the radioactive
label used. Stable Yttrium complexation requires 8 ligands while for Indium
7 ligands suffice. Cyclic dianhydride DTPA and site specific GYK DTPA are examples
of chelate-immunoconjugates with insufficient ligands for Yttrium chelation
and are ineffective therapeutic agents. 8
Iodine-131 is becoming a less attractive
radionuclide for RIT. Its half-life is long (8 days); its gamma emissions contain
high energy photons that decrease the accuracy of diagnostic scans; its beta
emissions are weak (0.61 MeV) and will deliver lower and more inhomogeneous
doses to larger tumor masses than isotopes with higher energy beta emissions.
In addition the volatile nature of Iodine can cause hazardous vapors in
radiopharmacy and patient rooms.
SIXTH INTERNATIONAL SYMPOSIUM ON AUTOLOGOUS BONE MARROW TRANSPLANTATION 99