Use of Integrated SPECT/CT Imaging for Tumor Dosimetry in I-131 Radioimmunotherapy: A Pilot Patient Study

Abstract Integrated systems combining functional (single-photon emission computed tomography; SPECT) imaging with anatomic (computed tomography; CT) imaging have the potential to greatly improve the accuracy of dose estimation in radionuclide therapy. In this article, we present the methodology for highly patient-specific tumor dosimetry by utilizing such a system and apply it to a pilot study of 4 follicular lymphoma patients treated with I-131 tositumomab. SPECT quantification included three-dimensional ordered-subset expectation-maximization reconstruction and CT-defined tumor outlines at each time point. SPECT/CT images from multiple time points were coupled to a Monte Carlo algorithm to calculate a mean tumor dose that incorporated measured changes in tumor volume. The tumor shrinkage, defined as the difference between volumes drawn on the first and last CT scan (a typical time period of 15 days) was in the range 5%-49%. The therapy-delivered mean tumor-absorbed dose was in the range 146-334cGy. For comparison, the therapy dose was also calculated by assuming a static volume from the initial CT and was found to underestimate this dose by up to 47%. The agreement between tracer-predicted and therapy-delivered tumor-absorbed dose was in the range 7%-21%. In summary, malignant lymphomas can have dramatic tumor regression within days of treatment, and advanced imaging methods allow for a highly patient-specific tumor-dosimetry calculation that accounts for this regression.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78152/1/cbr.2008.0568.pd

Prospective SPECT-CT organ dosimetry-driven radiation-absorbed dose escalation using the In-111 (111In)/yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin ®) theranostic pair in patients with lymphoma at myeloablative dose levels

PURPOSE: We prospectively evaluated the feasibility of SPECT-CT/planar organ dosimetry-based radiation dose escalation radioimmunotherapy in patients with recurrent non-Hodgkin\u27s lymphoma using the theranostic pair of METHODS: 24 patients with CD20-positive relapsed or refractory rituximab-sensitive, low-grade, mantle cell, or diffuse large-cell NHL, with normal organ function, platelet counts \u3e 75,000/mm RESULTS: Patient-specific hybrid SPECT/CT + planar organ dosimetry was feasible in all 18 cases and used to determine the patient-specific therapeutic dose and guide dose escalation (26.8 ± 7.3 MBq/kg (mean), 26.3 MBq/kg (median) of CONCLUSIONS: Patient-specific outpatien

A computational method for internal radiation dosimetry at the voxel level

The current development of hybrid SPECT/CT and PET/CT systems allows not only accurate attenuation correction of images, but also provide an anatomical frame for the 3D spatial representation of the dose distribution. The main goal of this thesis project was to develop computational algorithms for calculation of the 3D dose distribution delivered by internal emitters based on the images and information provided by new hybrid SPECT/CT and PET/CT systems. Although many experimental problems exist in patient-specific dosimetry, current drawback is the lack of radionuclide voxel S values for the set of all possible combinations of cubical and non-cubical pixel edges and thickness used in SPECT and PET studies. This work presents an alternative and computationally efficient method for calculating voxel S values based on the Monte Carlo volume integration of tabulated dose point-kernels of beta emissions over a voxel-to-voxel geometry. The accuracy of the calculations was compared with those determined by direct Monte Carlo radiation transport simulation

Voxel-level dosimetry of 177Lu-octreotate : from phantoms to patients

In radionuclide therapy, the patient is injected with relatively high amounts of therapeutic radiopharmaceutical which localises to target tissue and emits ionising radiation. Unfortunately, a perfectly targeting radiopharmaceutical has not been discovered and part of the radiopharmaceutical accumulates to healthy tissues, which are also thus irradiated. In order to ensure safe use, the absorbed dose of radiation-sensitive organs must be monitored. The focus of this thesis is on patient specific dosimetry of lutetium-177 (Lu-177) labelled somatostatin analogue Lu-177-DOTA-Tyr3-octreotate (Lu-177-DOTATATE) treatments and development of internal dosimetry software. Lu-177-DOTATATE is a radiopharmaceutical that binds to somatostatin receptors and is used to treat patients with metastatic neuroendocrine tumours. Recent studies have shown significant treatment outcome improvements with Lu-177-DOTATATE when compared to previously used somatostatin analogue treatments. However, the kidneys are the healthy organ which receives the highest amount of radiation dose from Lu-177-DOTATATE treatments and could be the organ that limits the number of treatments a patient can tolerate. In addition, absorbed dose to kidneys varies highly from patient to patient and thus patient specific dosimetry is recommended. Despite many years of dosimetry research and the existence of several published scientific dosimetry tools, there is no clinically validated kidney dosimetry software for Lu-177-DOTATATE treatments. The aim of this thesis was to study quantification accuracy of Lu-177 radionuclide using SPECT/CT imaging and to study mean absorbed doses to kidneys and dose distribution characteristics of Lu-177-DOTATATE. A streamlined voxel level absorbed dose software for clinical practice was developed and validated for kidney dosimetry of Lu-177-DOTATATE treatments. The effect of reconstruction methods on Lu-177 quantification accuracy was studied using an anthropomorphic phantom with known Lu-177 sources. Acquired data were reconstructed using different image compensation methods and results were compared with known source activities in the phantom. It was found that Monte Carlo simulation based scatter compensation and SPECT detector response compensation improved Lu-177 quantification accuracy considerably. Similar findings were also observed with data from patients treated with Lu-177-DOTATATE. A Monte Carlo simulation study was carried out to investigate absorbed dose distribution of Lu-177. Two main findings were that electrons emitted by Lu-177 can be assumed to absorb locally when the resolution of the imaging system is taken into account and the photon cross-irradiation can contribute significantly to total absorbed dose especially in the vicinity of highly active volumes. Using Lu-177-DOTATATE patient data, two different kidney absorbed dose calculation methods were compared. Comparing the mean kidney absorbed dose with the estimated maximum absorbed dose, it was observed that Lu-177-DOTATATE accumulates unevenly to kidney causing significantly heterogeneous dose distribution within kidneys. In addition, a simplified imaging protocol was found to be adequate for dosimetry purposes and was later adopted clinical practice. Combining previous findings new voxel level dosimetry software was developed. The clinical feasibility of the proposed software was tested with digital phantom simulations and reanalysing patient data from Lu-177-DOTATATE treatments. The software was found to be reliable and to speed up and simplify the dosimetry workflow.Lutetium-177 (Lu-177) -oktreotaattihoito on tehokas hoitomenetelmä levinneisiin neuroendokriinisiin kasvaimiin. Suonensisäisesti annettava Lu-177 -isotoopilla leimattu oktreotaatti sitoutuu kasvaimien pinnalla ilmeneviin somatostatiinireseptoreihin ja Lu-177:n emittoima elektronisäteily tuhoaa syöpäsolukkoa. Paikallisesti ionisoivan elektronisäteilyn lisäksi Lu-177 emittoi myös gammasäteilyä, joka voidaan kuvantaa gammakameralla potilaan ulkopuolelta. Oktreotaatti sitoutuu pieninä määrinä myös terveisiin kudoksiin. Sitoutumaton lääke erittyy munuaisten kautta virtsaan, minkä seurauksena munuaiset voivat saada hoidoista suuren säteilyannoksen. Tämä voi johtaa munuaisten vajaatoimintaan. Munuaisiin kertyvän radiolääkkeen määrä vaihtelee suuresti potilaiden välillä, minkä vuoksi munuaisiin kohdistuvaa säderasitusta tulee seurata potilaskohtaisesti. Tämän väitöskirjan tavoite oli kehittää annoslaskentaohjelma radionuklidihoitoihin keskittyen Lu-177 -oktreotaattihoitoihin. Työssä tutkittiin Lu-177 -aktiivisuuden määrityksen tarkkuutta SPECT-TT-kuvauksilla ja eri kuvarekonstruktiomenetelmien vaikutusta aktiivisuuden määrityksen suorituskykyyn. Monte Carlo -simuloinneilla tutkittiin Lu-177:n elektroni- ja gammasäteilyn annosjakaumia. Kliinisesti käytössä olevilla annoslaskentamenetelmillä vertailtiin Lu-177 -oktreotaattihoidettujen potilaiden munuaisannoksia ja annosten vaihtelua hoitokertojen välillä. Yhdistämällä näiden töiden tulokset kehitettiin uusi potilaan yksilöllisiin SPECT-TT-kuviin perustuva annoslaskentaohjelma. Työssä osoitettiin, että kuvarekonstruktiossa käytettävillä kompensaatiomenetelmillä on huomattava vaikutus Lu-177:n aktiivisuuden määrityksen tarkkuuteen etenkin pienten kohteiden kohdalla. Tarkimmat tulokset saavutettiin yhdistämällä kuvarekonstruktioon vaimennuskorjaus, sirontakorjaus ja kollimaattori-detektori-vastemallinnus. Monte Carlo -simulointien avulla havaittiin elektronisäteilyn kantaman olevan häviävän pieni verrattuna gammakameran erotuskykyyn. Tämän takia SPECT-kuviin perustuvassa Lu-177:n annoslaskennassa voidaankin olettaa elektronien absorboituvan paikallisesti. Toisaalta simuloinneissa havaittiin, että hyvin aktiivisista lähteistä aiheutuu suuri gammasäteilyannos, joka tulisi ottaa huomioon annoslaskennassa. Lu-177 -oktreotaattihoidettujen potilaiden munuaisten säteilyannokset vaihtelivat suuresti. Potilaskuvista määritetyistä annosjakaumista havaittiin, että munuaisten keskimääräinen annos ja maksimiannos erosivat toisistaan tilastollisesti merkitsevästi. Radionuklidihoitojen annoslaskenta on monivaiheinen prosessi, jossa SPECT-kuvaus- ja rekonstruktiomenetelmät ovat keskeisessä asemassa. Tämän lisäksi annoslaskenta- ja analyysimenetelmien tulee olla käyttötarkoitukseen validoituja. Väitöskirjassa esitetty annoslaskentaohjelma mahdollistaa potilaan yksilöllisiin SPECT-TT-kuviin perustuvan annoslaskennan. Ohjelma validoitiin Lu-177 -oktreotaattihoitojen munuaisannoksen määrittämiseen, mutta sen kehittäminen muiden radionuklidien annoslaskentaan on mahdollista. Ohjelmiston kehitys on tehty yhteistyössä HERMES Medical Solution -yrityksen kanssa ja ohjelma tulee kaupallisesti saataville