Page 165 - 89Zr-Immuno-PET:Towards a Clinical Tool to Guide Antibody-based Therapy in Cancer

89Zr-immuno-PET in a phase I trial
all radioactivity concentrations were converted to antibody concentrations by the following formula: CmAb = (AC / ID) * DmAb, where CmAb is the mAb concentration in mg/mL and DmAb is the total (=labeled + unlabeled) antibody dose administered in mg.
All measured time points were combined to derive a time antibody concentration curve. Subsequently, using trapezoidal integration, the AUC in mg·h·mL-1 was calculated. For each tissue, the tissue-to-blood AUC ratio was obtained by dividing the tissue AUC by the blood pool AUC. Data, averaged over the number of patients per dose cohort, are presented as mean ± SD.
RESULTS
Patient characteristics
Thirteen patients with advanced CD44-expressing solid tumors were included. Five cohorts with different doses of antibody were evaluated: 1 mg (n=1), 100 mg (n=3), 200 mg (n=2), 450 mg (n=5) and 675 mg (n=2). These dose cohorts were determined based on safety as assessed in the main phase I trial. Subsequently, the imaging dose was increased when imaging and tumor characteristics were not satisfactory (e.g. no visible tumor uptake due to uptake in normal tissues/high background). Patient details are provided in Table 1. In each case CD44 expression was confirmed by central reviewing of tumor biopsies (Figure 1S in Supplementary Data).
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Table 1 Patient details
Patient Gender Tumor type
CD44 expression (IHC)
1 F
2 M
3 M
4 M
5 M
6 F
7 M
8 M
9 M
10 M
11 F
12 M
13 M
squamous cell carcinoma cervix adenocarcinoma oesophagus colorectal carcinoma melanoma
colorectal carcinoma
squamous cell carcinoma cervix basaloid carcinoma tonsil
squamous cell carcinoma oesophagus colorectal carcinoma cholangiocarcinoma
squamous cell carcinoma earcanal colorectal carcinoma
colorectal carcinoma
Membrane Score 3
2 (focal)
2 (focal)
3
2
2 (focal) 3
3
2
3
3
2 (focal) 3
H-Score Biopsy location 285 lung
30 oesophagus
25 liver
250 liver
130 peritoneal 65 cervix 135 lung
210 neck left 85 liver
200 liver
260 neck left 35 liver
218 liver
163