Direct intratumoral infusion of liposome encapsulated rhenium radionuclides for cancer therapy: Effects of nonuniform intratumoral dose distribution

Journal Article · Tue Mar 15 00:00:00 EDT 2011 · Medical Physics

DOI:https://doi.org/10.1118/1.3552923· OSTI ID:22096924

Hrycushko, Brian A.; Shihong, Li; Goins, Beth; Otto, Randal A.; Bao, Ande ^[1]

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1. Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229 (United States)

Purpose: Focused radiation therapy by direct intratumoral infusion of lipid nanoparticle (liposome)-carried beta-emitting radionuclides has shown promising results in animal model studies; however, little is known about the impact the intratumoral liposomal radionuclide distribution may have on tumor control. The primary objective of this work was to investigate the effects the intratumoral absorbed dose distributions from this cancer therapy modality have on tumor control and treatment planning by combining dosimetric and radiobiological modeling with in vivo imaging data. Methods: {sup 99m}Tc-encapsulated liposomes were intratumorally infused with a single injection location to human head and neck squamous cell carcinoma xenografts in nude rats. High resolution in vivo planar imaging was performed at various time points for quantifying intratumoral retention following infusion. The intratumoral liposomal radioactivity distribution was obtained from 1 mm resolution pinhole collimator SPECT imaging coregistered with CT imaging of excised tumors at 20 h postinfusion. Coregistered images were used for intratumoral dosimetric and radiobiological modeling at a voxel level following extrapolation to the therapeutic analogs, {sup 186}Re/{sup 188}Re liposomes. Effective uniform dose (EUD) and tumor control probability (TCP) were used to assess therapy effectiveness and possible methods of improving upon tumor control with this radiation therapy modality. Results: Dosimetric analysis showed that average tumor absorbed doses of 8.6 Gy/MBq (318.2 Gy/mCi) and 5.7 Gy/MBq (209.1 Gy/mCi) could be delivered with this protocol of radiation delivery for {sup 186}Re/{sup 188}Re liposomes, respectively, and 37-92 MBq (1-2.5 mCi)/g tumor administered activity; however, large intratumoral absorbed dose heterogeneity, as seen in dose-volume histograms, resulted in insignificant values of EUD and TCP for achieving tumor control. It is indicated that the use of liposomes encapsulating radionuclides with higher energy beta emissions, dose escalation through increased specific activity, and increasing the number of direct tumor infusion sites improve tumor control. For larger tumors, the use of multiple infusion locations was modeled to be much more efficient, in terms of activity usage, at improving EUD and TCP to achieve a tumoricidal effect. Conclusions: Direct intratumoral infusion of beta-emitting radionuclide encapsulated liposomes shows promise for cancer therapy by achieving large focally delivered tumor doses. However, the results of this work also indicate that average tumor dose may underestimate tumoricidal effect due to substantial heterogeneity in intratumoral liposomal radionuclide distributions. The resulting intratumoral distribution of liposomes following infusion should be taken into account in treatment planning and evaluation in a clinical setting for an optimal cancer therapy.

• OSTI ID: 22096924
• Journal Information: Medical Physics, Vol. 38, Issue 3; Other Information: (c) 2011 American Association of Physicists in Medicine; Country of input: International Atomic Energy Agency (IAEA); ISSN 0094-2405
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
61 RADIATION PROTECTION AND DOSIMETRY
60 APPLIED LIFE SCIENCES
CARCINOMAS
CONTROL
DISTRIBUTION
DOSIMETRY
HEAD
IN VIVO
INFUSION
LIPOSOMES
NECK
RADIATION DOSE DISTRIBUTIONS
RADIATION DOSES
RADIONUCLIDE KINETICS
RADIOTHERAPY
RATS
RHENIUM 186
RHENIUM 188
SIMULATION
SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY
TECHNETIUM 99