PHARMACOKINETICS, BIODISTRIBUTION, AND DOSIMETRY OF SPECIFIC AND CONTROL RADIOLABELED MONOCLONAL-ANTIBODIES IN PATIENTS WITH PRIMARY HEAD AND NECK SQUAMOUS-CELL CARCINOMA
A. Maraveyas et al., PHARMACOKINETICS, BIODISTRIBUTION, AND DOSIMETRY OF SPECIFIC AND CONTROL RADIOLABELED MONOCLONAL-ANTIBODIES IN PATIENTS WITH PRIMARY HEAD AND NECK SQUAMOUS-CELL CARCINOMA, Cancer research, 55(5), 1995, pp. 1060-1069
The pharmacokinetics, biodistribution, and dosimetry of an IgG1 radiol
abeled anti-mucin mAb (HMFG1) and an isotype-matched control (4D513) w
ere studied in 29 patients with primary head and neck squamous cell ca
rcinoma. Patients were given injections at 3 fixed time points prior t
o surgery, i.e., 24 (n = 12), 48 (n = 9), or 72 (n = 8) h. They were s
ubsequently classified into two groups based on their immunohistochemi
cal positivity for polymorphic epithelial mucin, Fourteen patients (48
%) were positive, 5 of which were studied with both antibodies; and 15
patients were negative (52%), 7 of which were studied with both antib
odies, There was no significant difference in serum pharmacokinetics a
nd cumulative urinary clearance of the two antibodies, There was no si
gnificant difference in overall normal tissue uptake of specific and c
ontrol antibody; however, when each component of the normal tissue cat
egory was analyzed individually, there was a significantly increased u
ptake of HMFG1 in mucosa as compared to control antibody, Immunohistoc
hemical studies revealed positive staining of mucosa with HMFG1. There
was significantly increased uptake of specific antibody in antigen-po
sitive tumors as compared to uptake of control antibody (P < 0.02). A
tendency for less label loss over time from positive tumors as compare
d to control was documented, Absolute antibody uptake and tumor/normal
tissue ratios demonstrated significant overlap in individual patients
from each category depending on the specific ratio (e.g., tumor/adipo
se tissue) or time point studied; hence arbitrary cutoff values could
not be recommended as indicators of specific uptake, Specificity and l
ocalization indices were the most reproducible indicators of specific
localization. Areas under the curve were calculated for all tissues, a
nd Local dosimetry for the two beta-emitting isotopes I-131 and Y-90 i
s presented. The D-eq values for antigen-positive tumors were 2.9 cGy/
mCi for I-131 and 9.0 cGy/mCi injected for Y-90. For antigen-negative
tumors these values were significantly lower at 0.83 and 2.4 cGy/mCi o
f I-131 and Y-90, respectively. Bone marrow D-eq was calculated to be
0.87 cGy/mCi of I-131-HMFG1 injected. Because the purpose of our ongoi
ng research is to assess the therapeutic potential of the combination
of radiolabeled antibody and external radiotherapy, detailed dose calc
ulation to local dose-limiting tissues is required, D-eq to mucosa was
calculated to be 1.1 and 3.8 cGy/mCi of injected I-131 and Y-90, resp
ectively. We conclude that a 9-10-Gy dose increment may be achieved in
two administrations of 150 mCi of I-131-HMFG1 during a course of exte
rnal radiotherapy, This may lead to improved control of local disease
in patients with head and neck cancer.