Biodistribution and radiation dosimetry of 11C-labelled docetaxel in cancer patients

Abstract

Purpose: Docetaxel is an important chemotherapeutic agent used for the treatment of several cancer types. As radiolabelled anticancer agents provide a potential means for personalized treatment planning, docetaxel was labelled with the positron emitter (11)C. Non-invasive measurements of [(11)C]docetaxel uptake in organs and tumours may provide additional information on pharmacokinetics and pharmacodynamics of the drug docetaxel. The purpose of the present study was to determine the biodistribution and radiation absorbed dose of [(11)C]docetaxel in humans.

Methods: Biodistribution of [(11)C]docetaxel was measured in seven patients (five men and two women) with solid tumours using PET/CT. Venous blood samples were collected to measure activity in blood and plasma. Regions of interest (ROI) for various source organs were defined on PET (high [(11)C]docetaxel uptake) or CT (low [(11)C]docetaxel uptake). ROI data were used to generate time-activity curves and to calculate percentage injected dose and residence times. Radiation absorbed doses were calculated according to the MIRD method using OLINDA/EXM 1.0 software.

Results: Gall bladder and liver demonstrated high [(11)C]docetaxel uptake, whilst uptake in brain and normal lung was low. The percentage injected dose at 1 h in the liver was 47 +/- 9%. [(11)C]docetaxel was rapidly cleared from plasma and no radiolabelled metabolites were detected. [(11)C]docetaxel uptake in tumours was moderate and highly variable between tumours.

Conclusion: The effective dose of [(11)C]docetaxel was 4.7 microSv/MBq. As uptake in normal lung is low, [(11)C]docetaxel may be a promising tracer for tumours in the thoracic region.

Fig. 1

For organs with activity clearly exceeding background (e.g. liver) ROIs were defined on the PET scan with the highest uptake. PET/CT fusion image (a) and PET image (b) demonstrate high [¹¹C]docetaxel uptake in liver. The liver ROI as determined on the PET image is presented in green (b)

Fig. 2

For organs with lower tracer uptake (e.g. lung), ROIs were drawn on the LD-CT scan and subsequently copied onto the PET scans. PET/CT fusion image (a) and PET image demonstrate low [¹¹C]docetaxel uptake in lungs. The lung ROIs were drawn on the CT image (b) and projected onto the PET image (c). The lung ROIs as determined on the LD-CT scan are presented in green (b, c)

Fig. 3

Maximum intensity projections of the biodistribution of [¹¹C]docetaxel in a 71-year-old male patient with metastatic malignant pleural mesothelioma. The four successive whole-body PET scans (0–6, 8–19, 23–39 and 42–63 min p.i.) demonstrate high liver uptake at all time points and low uptake in brain and normal lung. On the fourth scan, [¹¹C]docetaxel uptake is observed in intestine

Fig. 4

Decay-corrected TACs of [¹¹C]docetaxel (%ID versus time p.i.) (n = 7) in a liver, b ULI and gall bladder, c brain, lung, heart contents and myocardial wall, and d urinary bladder, spleen, kidney and red marrow. Vertical bars indicate standard deviation

Fig. 5

Decay-corrected TACs of [¹¹C]docetaxel (%ID/ml versus time p.i.) in plasma and whole blood

Fig. 6

PET/CT images of [¹¹C]docetaxel in a 71-year-old male patient with metastatic malignant pleural mesothelioma. Mediastinal metastasis (arrow) on CT scan (a) with [¹¹C]docetaxel uptake on PET scan (b) and on PET/CT fusion image (c)

Fig. 7

Decay-corrected TACs of [¹¹C]docetaxel for seven different tumours (SUV_max versus time p.i.) including mediastinal metastasis of malignant pleural mesothelioma (a), metastasis of NSCLC (b, d), primary tumour of NSCLC (c, e, f) and lung metastasis of prostate cancer (g)

Fig. 8

Total activity (non-decay-corrected) in gall bladder in a single patient who underwent an additional fifth whole-body scan. Solid lines show the interpolated data from which the trapezoidal integral was computed, assuming physical decay after the fourth whole-body scan, whereas dashed lines show the integral after inclusion of the fifth whole-body scan