Article

177Lu-[DOTA0,Tyr3] octreotate therapy in patients with disseminated neuroendocrine tumors: Analysis of dosimetry with impact on future therapeutic strategy.

Department of Oncology, Lund University and Lund University Hospital, Lund, Sweden.
Cancer (Impact Factor: 4.9). 02/2010; 116(4 Suppl):1084-92. DOI: 10.1002/cncr.24796
Source: PubMed

ABSTRACT (177)Lu-(DOTA0,Tyr3) octreotate is a new treatment modality for disseminated neuroendocrine tumors. According to a consensus protocol, the calculated maximally tolerated absorbed dose to the kidney should not exceed 27 Gy. In commonly used dosimetry methods, planar imaging is used for determination of the residence time, whereas the kidney mass is determined from a computed tomography (CT) scan.
Three different quantification methods were used to evaluate the absorbed dose to the kidneys. The first method involved common planar activity imaging, and the absorbed dose was calculated using the medical internal radiation dose (MIRD) formalism, using CT scan-based kidney masses. For this method, 2 region of interest locations for the background correction were investigated. The second method also included single-photon emission computed tomography (SPECT) data, which were used to scale the amplitude of the time-activity curve obtained from planar images. The absorbed dose was calculated as in the planar method. The third method used quantitative SPECT images converted to absorbed dose rate images, where the median absorbed dose rate in the kidneys was calculated in a volume of interest defined over the renal cortex.
For some patients, the results showed a large difference in calculated kidney-absorbed doses, depending on the dosimetry method. The 2 SPECT-based methods generally gave consistent values, although the calculations were based on different assumptions. Dosimetry using the baseline planar method gave higher absorbed doses in all patients. The values obtained from planar imaging with a background region of interest placed adjacent to the kidneys were more consistent with dosimetry also including SPECT. For the accumulated tumor absorbed dose, the first 2 of the 4 planned therapy cycles made the major contribution.
The results suggested that patients evaluated according to the conventional planar-based dosimetry method may have been undertreated compared with the other methods. Hematology and creatinine did not indicate any restriction for a more aggressive approach, which would be especially useful in patients with more aggressive tumors where there is not time for more protracted therapy.

Download full-text

Full-text

Available from: Sven-Erik Strand, Dec 30, 2014
0 Followers
 · 
130 Views
  • Source
    • "When 90 Y is the radiopharmaceutical, either 111 In-or 86 Y-labeled peptides are used as a surrogate and 2 to 5 scans are collected up to 2-3 days p.i. [3]. These activity data are usually fitted by means of monoexponential functions [4] [5] [6], biexponential [3], or trapezoids [7]. The great value of dosimetry is an established tenet, nonetheless each experimental point requires time-consuming acquisitions. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Kidney dosimetry in 177Lu and 90Y PRRT requires 3 to 6 whole-body/SPECT scans to extrapolate the peptide kinetics, and it is considered time and resource consuming. We investigated the most adequate timing for imaging and time-activity interpolating curve, as well as the performance of a simplified dosimetry, by means of just 1-2 scans. Finally the influence of risk factors and of the peptide (DOTATOC versus DOTATATE) is considered. 28 patients treated at first cycle with 177Lu DOTATATE and 30 with 177Lu DOTATOC underwent SPECT scans at 2 and 6 hours, 1, 2, and 3 days after the radiopharmaceutical injection. Dose was calculated with our simplified method, as well as the ones most used in the clinic, that is, trapezoids, monoexponential, and biexponential functions. The same was done skipping the 6 h and the 3 d points. We found that data should be collected until 100 h for 177Lu therapy and 70 h for 90Y therapy, otherwise the dose calculation is strongly influenced by the curve interpolating the data and should be carefully chosen. Risk factors (hypertension, diabetes) cause a rather statistically significant 20% increase in dose (t-test, P < 0.10), with DOTATATE affecting an increase of 25% compared to DOTATOC (t-test, P < 0.05).
    06/2013; 2013:935351. DOI:10.1155/2013/935351
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Paragangliomas are rare tumors of neural crest origin. They are benign in the majority of cases and are characterized by a strong vascularisation. In the head and neck region they most commonly occur as carotid body tumors. Jugulotympanic and especially vagal paragangliomas are seen less frequently. Complete surgical resection represents the only curative treatment option even though resection of locally advanced tumors regularly results in lesions of the lower cranial nerves and major vessels. Appoximately 30% of all head and neck paragangliomas (HNPs) are hereditary and associated with different tumor syndromes. The paraganglioma syndromes 1, 3 and 4 (PGL 1, 3 and 4) make up the majority of those familial cases. PGL 1 is associated with mutations of the succinate dehydrogenase subunit D (SDHD) gene, PGL 3 is caused by SDHC and PGL 4 by SDHB gene mutations. Multiple HNPs and the occurance of HNPs together with pheochromocytomas are seen in SDHD as well as SDHB mutation carriers. In patients with SDHB mutations the risk for the development of malignant paraganglial tumors is significantly higher compared to SDHC and SDHD patients as well as patients with sporadic tumors. SDHC mutation carriers almost exclusively present with benign HNP that are unifocal in the majority of cases. The role of transmission is autosomal dominant for all three symptoms. Interestingly, there is a “parent-of-origin-dependent-inheritance” in subjects with SDHD gene mutations. This means that the disease phenotype may only become present if the mutation is inherited through the paternal line. We recommend screening for mutations of the genes SDHB, SDHC and SDHD in patients with HNPs. Certain clinical parameters can help to set up the order in which the three genes should be tested.
    01/2011; 10:Doc03. DOI:10.3205/cto000076
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The combination of single photon emission computed tomography (SPECT) and computer tomography (CT) that incorporates iterative reconstruction algorithms with attenuation and scatter correction should facilitate accurate non-invasive quantitative imaging. Quantitative SPECT (QSPECT) may improve diagnostic ability and could be useful for many applications including dosimetry assessment. Using (177)Lu, we developed a QSPECT method using a commercially available SPECT/CT system. Serial SPECT of (177)Lu sources (89-12,400 MBq) were acquired with multiple contiguous energy windows along with a co-registered CT, and were reconstructed using an iterative algorithm with attenuation and scatter correction. Camera sensitivity (based on reconstructed SPECT count rate) and dead-time (based on wide-energy spectrum count rate) were resolved by non-linear curve fit. Utilizing these parameters, a SPECT dataset can be converted to a QSPECT dataset allowing quantitation in Becquerels per cubic centimetre or standardized uptake value (SUV). Validation QSPECT/CT studies were performed on a (177)Lu cylindrical phantom (7 studies) and on 5 patients (6 studies) who were administered a therapeutic dose of [(177)Lu]octreotate. The QSPECT sensitivity was 1.08 x 10(-5) ± 0.02 x 10(-5) s(-1) Bq(-1). The paralyzing dead-time constant was 0.78 ± 0.03 µs. The measured total activity with QSPECT deviated from the calibrated activity by 5.6 ± 1.9% and 2.6 ± 1.8%, respectively, in phantom and patients. Dead-time count loss up to 11.7% was observed in patient studies. QSPECT has high accuracy both in our phantom model and in clinical practice following [(177)Lu]octreotate therapy. This has the potential to yield more accurate dosimetry estimates than planar imaging and facilitate therapeutic response assessment. Validating this method with other radionuclides could open the way for many other research and clinical applications.
    Cancer Imaging 06/2011; 11(1):56-66. DOI:10.1102/1470-7330.2011.0012 · 1.29 Impact Factor
Show more