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 Table of Contents 
ORIGINAL ARTICLE
Year : 2016  |  Volume : 39  |  Issue : 4  |  Page : 194-198  

Correlation between dose rate and physical factors of patients undergoing peptide receptor radionuclide therapy with (Lu-177)-DOTATATE


1 Radiation Safety Systems Division, Bhabha Atomic Research Centre, Trombay, Mumbai, Maharashtra, India
2 Radiation Medicine Centre, Bhabha Atomic Research Centre, Trombay, Mumbai, Maharashtra, India

Date of Web Publication13-Feb-2017

Correspondence Address:
Kamaldeep
RHC Unit, Radiation Medicine Centre, Tata Memorial Centre Annexe Building, Jerbai Wadia Road, Parel, Mumbai - 400 012, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-0464.199974

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  Abstract 

In peptide receptor radionuclide therapy (PRRNT) for the treatment of neuroendocrine tumors with (Lu-177)-DOTATATE, large variations in dose rate at 1 m from the patient's body surface administered with same amount of Lu-177 activity are observed. The aim of this prospective study was to explain the cause of the variations and see if there is correlation between the dose rate per unit activity at 1 m distance from patient's body surface in PRRNT with (Lu-177)-DOTATATE and physical factors such as height, weight, age, body surface area (BSA), body mass index (BMI), height/weight (H/W) ratio, and BSA/BMI ratio. From this study, it is observed that dose rate per unit activity at 1 m distance from patient's body surface is significantly correlated with BMI, H/W ratio, and weight of the patients. Male and female patient's data were also separately analyzed, and there was no statistically significant difference observed in these groups of patients. As BMI or weight of the patient is increases, dose rate per unit activity at 1 m distance from patient's body surface decreases and as H/W ratio increases dose rate per unit activity at 1 m distance from patient's body surface also increases. Moderate correlation was seen with BSA and BSA/BMI ratio of the patients. No correlation was seen with age and height of the patients. From this study, H/W ratio can be considered as a good parameter for correlating the dose rate and activity retained in the patient's body. H/W ratio of patient affects the external dose measurement at 1 m from body surface immediately post-Lu-177 labeled PRRNT therapy. Thus, the study is important in formulating the regulatory criterion for discharge of patients after the treatment.

Keywords: (Lu-177)-DOTATATE, body mass index, body surface area, dose rate, peptide receptor radionuclide therapy


How to cite this article:
Kamaldeep, Kaisar S, Maletha P, Tervankar S, Gopalakrishnan R K, Basu S, Rajan M. Correlation between dose rate and physical factors of patients undergoing peptide receptor radionuclide therapy with (Lu-177)-DOTATATE. Radiat Prot Environ 2016;39:194-8

How to cite this URL:
Kamaldeep, Kaisar S, Maletha P, Tervankar S, Gopalakrishnan R K, Basu S, Rajan M. Correlation between dose rate and physical factors of patients undergoing peptide receptor radionuclide therapy with (Lu-177)-DOTATATE. Radiat Prot Environ [serial online] 2016 [cited 2020 Sep 19];39:194-8. Available from: http://www.rpe.org.in/text.asp?2016/39/4/194/199974


  Introduction Top


Peptide receptor radionuclide therapy (PRRNT) is a molecular targeted radiation therapy involving the systemic administration of radiolabeled somatostatin analogs such as (177-Lu)-DOTATATE. These molecules are designed to target with high affinity and specificity somatostatin receptors overexpressed on tumors. PRRNT with radiolabeled somatostatin analogs has been shown to be an effective treatment in patients with metastatic neuroendocrine tumors (NET's).[1],[2],[3],[4],[5] PRRNT employing the radio-tagged somatostatin receptors agonists (Lu-177)-DOTATATE has been successfully used in Radiation Medicine Centre for the past over 5 years to target metastatic or inoperable NET's expressing the somatostatin receptor. For the treatment of NET's, patients are treated with a therapeutic dose of 4.44–8.73 GBq of (Lu-177)-DOTATATE. The radiological half-life of Lu-177 is 161.0 h.[6] It decays by beta particles emissions (Emax = 498 keV [79.4%], 177 keV [11.6%], 385 keV [9.0%], and 249 keV [0.006%]) and gamma radiation emissions (208 keV [11.1%], 113 keV [6.2%], and 321 keV [0.2%]).[7] Other emissions with lower intensities are not mentioned here. Gamma radiations emitted from the Lu-177 are contributing to the external radiation dose emitted from the patients treated with (Lu-177)-DOTATATE and contributing external exposure to the family members and persons who come in close contact with such patients. As per the institution policy, these patients are hospitalized in isolation room for 1 day. Data available about dose rate at 1 m distance from patients in PRRNT with (Lu-177)-DOTATATE are scarce. A large variation in dose rate per unit activity at 1 m from the patient's body surface, administered with same amount of Lu-177 activity, is found among various patients. The aim of this prospective study was to explain the cause of the variations and see if there is correlation between the dose rate per unit activity at 1 m distance from patient's body surface in PRRNT with (Lu-177)-DOTATATE and physical factors such as height, weight, age, body surface area (BSA), body mass index (BMI), height/weight (H/W) ratio, and BSA/BMI ratio. In literature of radioiodine treatment, there are studies where different models are used to study the correction factors for more accurate estimates of exposure rates near radioactive patients.[8],[9] Yi et al.[10] used self-shielding factors to obtain the ratio of calculated/measured exposure rates near thyroid cancer patients receiving I-131, patients receiving 18 F-fludeoxyglucose, and patients receiving (99m Tc)-radiopharmaceuticals. Correlation between physical factors and dose rate can be used for more accurate estimates of exposure rates near radioactive patients.


  Materials and Methods Top


Patients

Sixty-seven patients from all over India, with NET expressing somatostatin receptors, who underwent 105 therapeutic procedures (2 patients underwent 4 treatment cycles, 6 patients underwent 3 treatment cycles, 20 patients underwent 2 treatment cycles, and 39 patients underwent 1 treatment cycle), were the cohorts of this study. Twenty-three patients were females (40 therapeutic procedures) and forty-four patients were males (65 therapeutic procedures).

Dose rate measurement

After the administration of (Lu-177)-DOTATATE through infusion over a period of 25–30 min, the dose rate at 1 m distance from the patient's body surface (scanned from head to toe and the maximum value is recorded) was taken using plastic scintillator detector based AT1121 Atomtex make radiation survey meter (sensitivity for 137 Cs is 70 cps/µSv/h). The dose rate obtained is normalized with the amount of radioactivity administered.

Physical parameters

This study investigates the factors influencing the dose rate at 1 m distance from patient's body surface. Several physical parameters such as height, weight, age, BSA, BMI, H/W ratio, and BSA/BMI ratio are chosen as parameters. Before dosage administration, height and weight are measured, and their age was recorded. The mean ± 1 standard deviation (SD) and ranges are given in [Table 1].
Table 1: Patient's physical characteristics

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Body surface area and body mass index

In physiology and medicine, the BSA which is the measured or calculated surface area of a human body has various clinical purposes as it serves as a better indicator of metabolic mass than body weight because it is less affected by abnormal adipose mass.[11] Different mathematical formulations are available for predicting surface area from measurements of height and weight of the individual.[12] Following empirical expression was used in this work for estimating the BSA of the patients from the measured H and W:



The BMI provides a simple numeric measure of a person's thickness or thinness. The ratio of weight to height squared, here termed the BMI.[13]

BMI was calculated using the following relation:



Statistical analysis

Pearson's correlation coefficient [14] was calculated for height and dose rate, weight and dose rate, BSA and dose rate, BMI and dose rate, age and dose rate, H/W ratio and dose rate, and BSA/BMI ratio and dose rate using Origin Pro 8SRO. From Pearson's correlation coefficient, coefficient of determination was also calculated. A P ≤ 0.05 was considered significant.


  Results and Discussions Top


The range and mean ± 1SD of BSA, BMI, and radioactivity administered and dose rate per unit activity at 1 m distance from the patient body are presented in [Table 2].
Table 2: Patient's parameters

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From the study, it is observed that dose rate per unit activity at 1 m distance from patient's body surface is significantly correlated [15] with weight of the patient [Figure 1]a; the observed value of correlation coefficient is found to be 0.68. As weight of the patient is increases dose rate per unit activity at 1 m distance from patient's body surface decreases, there was no correlation observed with age [Figure 1]b and height [Figure 1]c of the patient. In case of derived parameters such as BSA, BMI, H/W ratio, and BSA/BMI ratio of the patients, dose rate per unit activity at 1 m distance from patient's body surface is significantly correlated with H/W ratio [Figure 1]d and BMI [Figure 1]e of the patients; the observed value of correlation coefficient is found to be 0.71and 0.64, respectively. Moderate correlation of dose rate per unit activity at 1 m distance from patient's body surface is seen with BSA [Figure 1]f of the patients, and poor correlation of dose rate per unit activity at 1 m distance from patient's body surface is seen with BSA/BMI [Figure 1]g of the patients. Male and female patient's data were also separately analyzed, and there was no statistical difference observed in these groups of patients. All the statistical results, namely, correlation coefficient (r), coefficient of determination (r2), P value, intercept, slope, and number of data points are presented in [Table 3]. From the statistical parameters obtained from this study, a fit equation is generated which correlate the H/W ratio with the dose rate at 1 m distance from the patient, treated with (Lu-177)-DOTATATE.
Figure 1: Correlation between the dose rate per unit activity and weight (a), age (b), height (c), height/weight ratio (d), body mass index (e), body surface area (f), and body surface area/body mass index (g) in patients treated with (Lu-177)-DOTATATE

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Table 3: Patient's statistical data (n=105)

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Where, D = Dose rate per unit activity at 1 m distance (µSv/h/GBq).

HW = Height/weight ratio (m/kg).

From this study, it is observed that the external dose rate per unit activity at 1 m distance from patient's body surface demonstrates the highest correlation with H/W ratio. As H/W ratio increases, dose rate per unit activity at 1 m distance from patient's body surface also increases. H/W ratio can be considered as a good parameter for correlating the dose rate and activity retained in the patient body; also it can be used as a marker for estimation of attenuation of the radiation by the body fat for external radiation exposure measurement, especially for the low-energy gamma emitted by Lu-177. This appears to be the most reasonable explanation for the wide variation in the dose rate at 1 m from the patient's body surface administered with same amount of Lu-177 activity.


  Conclusions Top


Increase in the H/W ratio of the patient increases the dose rate per unit activity at 1 m distance from patient's body surface. H/W ratio demonstrates the highest correlation with the dose rate per unit activity at 1 m from the surface of patient in PRRNT with (Lu-177)-DOTATATE. H/W ratio of patient affects the external dose measurement at 1 m from body surface immediately post-Lu-177 labeled PRRNT therapy. Results from this study indicate that this correlation of H/W ratio and dose rate per unit activity can be used to provide greater accuracy in estimating the exposure rate at 1 m distance from the surface of patients treated with Lu-DOTATATE. Thus, the study is important in formulating the regulatory criterion for discharge of patients after the treatment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Kwekkeboom DJ, Bakker WH, Kam BL, Teunissen JJ, Kooij PP, de Herder WW, et al. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA(0), Tyr3] octreotate. Eur J Nucl Med Mol Imaging 2003;30:417-22.  Back to cited text no. 1
    
2.
Kwekkeboom DJ, Teunissen JJ, Bakker WH, Kooij PP, de Herder WW, Feelders RA, et al. Radiolabeled somatostatin analog [177Lu-DOTA0, Tyr3] octreotate in patients with endocrine gastroenteropancreatic tumors. J Clin Oncol 2005;23:2754-62.  Back to cited text no. 2
    
3.
Kwekkeboom DJ, Mueller-Brand J, Paganelli G, Anthony LB, Pauwels S, Kvols LK, et al. Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs. J Nucl Med 2005;46 Suppl 1:62S-6S.  Back to cited text no. 3
    
4.
Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr3] octreotate: Toxicity, efficacy, and survival. J Clin Oncol 2008;26:2124-30.  Back to cited text no. 4
    
5.
Bodei L, Cremonesi M, Grana CM, Fazio N, Iodice S, Baio SM, et al. Peptide receptor radionuclide therapy with 177Lu-DOTATATE: The IEO phase I-II study. Eur J Nucl Med Mol Imaging 2011;38:2125-35.  Back to cited text no. 5
    
6.
Lederer CM, Shirley V. Table of Isotopes. 7th ed. New York: Wiley and Sons; 1978.  Back to cited text no. 6
    
7.
Kondev FG. Nuclear Data Sheets. Vol. 98; 2003. p. 824-77.  Back to cited text no. 7
    
8.
Willegaignon J, Guimarães MI, Stabin MG, Sapienza MT, Malvestiti LF, Marone MM, et al. Correction factors for more accurate estimates of exposure rates near radioactive patients: Experimental, point, and line source models. Health Phys 2007;93:678-88.  Back to cited text no. 8
    
9.
Siegel JA, Marcus CS, Sparks RB. Calculating the absorbed dose from radioactive patients: The line-source versus point-source model. J Nucl Med 2002;43:1241-4.  Back to cited text no. 9
    
10.
Yi Y, Stabin MG, McKaskle MH, Shone MD, Johnson AB. Comparison of measured and calculated dose rates near nuclear medicine patients. Health Phys 2013;105:187-91.  Back to cited text no. 10
    
11.
Available from: http://www.en.wikipedia.org/wiki/Body_surface_area. [Last accessed on 2012 Jun 07].  Back to cited text no. 11
    
12.
Dubois D, Dubois EF. A formula to estimate the approximate surface area if height and weight be known. Arch Int Med 1916;17:863-71.  Back to cited text no. 12
    
13.
Keys A, Fidanza F, Karvonen MJ, Kimura N, Taylor HL. Indices of relative weight and obesity. J Chronic Dis 1972;25:329-43.  Back to cited text no. 13
    
14.
Available from: http://www.pindling.org/Math/Statistics/Textbook/Chapter 3_Regression_Correlation. [Last accessed on 2012 Jun 07].  Back to cited text no. 14
    
15.
Taylor R. Interpretation of the correlation coefficient: A basic review. JDMS 1990;1:35-9.  Back to cited text no. 15
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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