A Whole Body Dosimetry Protocol for Peptide-Receptor Radionuclide Therapy (PRRT): 2D Planar Image and Hybrid 2D+3D SPECT/CT Image Methods

Summary

This method estimates the absorbed dose of different structures for peptide-receptor-radionuclide-therapy (PRRT) with the possibility of avoiding organ overlap on 2D-projections. Serial whole-body planar images permit estimation of mean absorbed doses along the whole body, while the hybrid approach, combining planar images and 3D-SPECT/CT image, overcomes the limitations of structure overlapping.

Abstract

Peptide-receptor-radionuclide-therapy (PPRT) is a targeted therapy that combines a short-range energy radionuclide with a substrate with high specificity for cancer cell receptors. After injection, the radiotracer is distributed throughout the entire body, with a higher uptake in tissues where targeted receptors are overexpressed. The use of beta/gamma radionuclide emitters enables therapy imaging (beta-emission) and post-therapy imaging (gamma-emission) to be performed at the same time. Post-treatment sequential images permit absorbed dose calculation based on local uptake and wash-in/wash-out kinetics. We implemented a hybrid method that combines information derived from both 2D and 3D images. Serial whole-body images and blood samples are acquired to estimate the absorbed dose to different organs at risk and to lesions disseminated throughout the body. A single 3D-SPECT/CT image, limited to the abdominal region, overcomes projection overlap on planar images of different structures such as the intestines and kidneys. The hybrid 2D+3D-SPECT/CT method combines the effective half-life information derived from 2D planar images with the local uptake distribution derived from 3D images. We implemented this methodology to estimate the absorbed dose for patients undergoing PRRT with ¹⁷⁷Lu-PSMA-617. The methodology could, however, be implemented with other beta-gamma radiotracers. To date, 10 patients have been enrolled into the dosimetry study with ¹⁷⁷Lu-PSMA-617 combined with drug protectors for kidneys and salivary glands (mannitol and glutamate tablets, respectively). The median ratio between kidney uptake at 24 h evaluated on planar images and 3D-SPECT/CT is 0.45 (range:0.32-1.23). The comparison between hybrid and full 3D approach has been tested on one patient, resulting in a 1.6% underestimation with respect to full 3D (2D: 0.829 mGy/MBq, hybrid: 0.315 mGy/MBq, 3D: 0.320 mGy/MBq). Treatment safety has been confirmed, with a mean absorbed dose of 0.73 mGy/MBq (range:0.26-1.07) for kidneys, 0.56 mGy/MBq (0.33-2.63) for the parotid glands and 0.63 mGy/MBq (0.23-1.20) for submandibular glands, values in accordance with previously published data.

Introduction

Among peptide-receptor radionuclide therapies, ¹⁷⁷Lu-PSMA-617 PRRT combines a short-range beta emitter ¹⁷⁷Lu (1.9 mm maximum range in water, half-life 6.71 days) with a prostate-specific membrane antigen (PSMA) ligand. The overexpression of PSMA in 90-100% of local prostate cancer lesions and metastatic disease (lymph node and bone) is the key to this therapy. However, PSMA receptors are also expressed in different healthy tissues where high uptake is often observed during treatments. The main organs at risk are the kidneys, red marrow, salivary and lachrymal glands. The dose to these organs may reduce maximum injectable activity, impairing the t....

Protocol

The dosimetry procedure was performed according to the treatment protocol "Radiometabolic Therapy (RMT) with ¹⁷⁷Lu-PSMA-617 in advanced castration resistant prostate cancer (CRPC): efficacy and toxicity evaluation" (EUDRACT/RSO number: 2016-002732-32) (Figure 1). Selected patients underwent dosimetry evaluation based on performance status. All patients signed informed consent. Prior to treatment delivery, each patient underwent a ⁶⁸Ga-PSMA-11 PET/CT whole body scan.

NOTE: It is important to underline that some steps are linked specifically to the scanner used.

1. ....

Results

Dosimetry was performed for 10 patients (7 undergoing first treatment cycle, 3 second cycle).  Blood samples were acquired from all but 3 patients. One patient voided the bladder before the first post-infusion image acquisition. Injected activity was 5.5 GBq for 5 patients and 4.4 GBq for 5 patients.

With regard to curve fitting, mono or bi-exponential curve fitting was used for organ time-activity-curves. Bi-exponential curve f.......

Discussion

The method described enables whole body dosimetry to be performed for PRRT therapies and is a valid compromise between 2D whole-body and 3D dosimetry information in that it provides valuable information without significantly increasing image acquisition load. The method is also useful for the evaluation of the absorbed dose of overlapping structures and provides information on the structures lying outside the 3D SPCET/CT limited field of view.

The implementation of the methodology requires a h.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
177Lu EndolucinBeta	ITG - Isotopen Technologien München AG, Lichtenbergstrasse 1, 85748 Garching, Germany, info@itm.ag		Radiotracer 177Lu for therapy purpuse
Biograph mCT Flow PET/CT	Siemens Healthineers, Erlangen, Germany		PET/CT scanner
C-Thru 57Co planar flood - Model MED3709	Eckert & Ziegler, Strahlen- und Medizintechnik AG, Robert-Rössle-Str. 10, 13125 Berlin, Germany, info@ezag.de		Calibration/planar source
Cylindrical phantom with spheric insert	Data Spectrum Corporation, 1605 East Club Boulevard, Durham NC 27704-3406, US, info@spect.com		Phantom for SPECT/CT calibration
Discovery NM/CT 670 SPECT/CT	International General Electric, General Electric Medical System, Haifa, Israel		SPECT/CT scanner
GalliaPharm 68Ge/68Ga Generator	Eckert & Ziegler, Strahlen- und Medizintechnik AG, Robert-Rössle-Str. 10, 13125 Berlin, Germany, info@ezag.de		68Ge/68Ga Generator of 68Ga for imaging purposes
GammaVision v 6.08	Ortec, Ametek - Advanced Measurement Technology, 801 South Illinois Avenue, Oak Ridge, Tennessee 37830, US, ortec.info@ametek.com		Gamma Spectorscopy software
High Purity Germanium HPGe, model GEM30P4-70	Ortec, Ametek - Advanced Measurement Technology, 801 South Illinois Avenue, Oak Ridge, Tennessee 37830, US, ortec.info@ametek.com		Gamma spectometer
MimVista Software	MIM Software INC, Cleveland, OH 44122, US		Workstation
OLINDA/EXM v 1.1	RADAR - RAdiation Dose Assessment Resource, West End Ave, Nashville, TN 37235, US (now commercially available as OLINDA/EXM v 2.0, Hermes Medical Solutions, Strandbergsgatan 16, 112 51 Stockholm, Sweden, info@hermesmedical.com)		Dosimetry software
PSMA 11	ABX advanced biochemical compounds - Biomedizinische,Heinrich-Gläser-Straße 10-14, 01454 Radeberg, Germania, info@abx.de		Carrier for 68Ga radiotracer
PSMA 617	Endocyte Inc. (Headquarters), 3000 Kent Avenue, West Lafayette, IN 47906		Carrier for 177Lu radiotracer
Xeleris4.0	International General Electric, General Electric Medical System, Haifa, Israel		Workstation