Evaluation of ¹⁸⁸Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

Figures & data

Figure 1 Relationship between F98_luc cell number and bioluminescent intensity (n=3).

Notes: (A) In vitro monitoring of bioluminescence of F98_luc cells via BLI. (B) In vitro cell growth curve of F98_luc cells. (C) Linear correlation between mean cell number and mean bioluminescent intensity (R²=0.99).

Abbreviations: BLI, bioluminescent imaging; T_d, doubling time; h, hours.

Figure 2 The Fischer344/F98_luc rat tumor growth curve as a function of bioluminescent intensity versus time (n=3).

Notes: (A) Non-invasive in vivo monitoring of tumor growth via BLI; (B) quantitative analysis of tumor growth with bioluminescent intensity; (C) the histopathological examination (H and E staining; photo with 40× magnification) of tumor parenchyma at Day 13 post-inoculation.

Abbreviations: BLI, bioluminescent imaging; H and E, hematoxylin and eosin; d, days.

Figure 3 The graphical representation of body weight monitoring of rats (n=5).

Notes: Normal Fischer344 rats administered 296 (▼), 333 (○), and 370 (•) MBq ¹⁸⁸Re-liposome via single intravenous injection.

Abbreviation: d, days.

Table 1 Equivalent dose of ¹⁸⁸Re-liposome in human organs estimated from extrapolation of orthotopic glioma-bearing rat model*

Organ	Estimated dose (mSv/MBq)
Adrenals	7.62E−02
Brain	2.75E−02
Breasts	7.09E−02
Gallbladder	7.61E−02
LLI wall	1.35E−01
Small intestine	2.01E−01
Stomach wall	1.19E−01
ULI wall	7.29E−02
Heart wall	8.89E−01
Kidneys	1.20E+00
Liver	8.11E−01
Lungs	4.26E−01
Muscle	2.55E−02
Ovaries	7.16E−02
Pancreas	1.32E−01
Red marrow	5.13E−02
Osteogenic cells	1.14E−01
Skin	6.97E−02
Spleen	6.96E+00
Testes	5.41E−02
Thymus	7.27E−02
Thyroid	7.04E−02
Urinary bladder wall	7.09E−02
Uterus	7.16E−02
Total body	1.35E−01
Effective dose	3.34E−01

Note:

* The OLINDA/EXM 1.1 software was applied in the radiation dosimetry with equivalent doses estimated for a 73 kg male adult.

Abbreviations: LLI, lower large intestine; ULI, upper large intestine.

Table 2 Therapeutic efficacy evaluation of 333 MBq ¹⁸⁸Re-liposome in orthotopic glioma-bearing rat model

Injection	No of rat/group	Dose (MBq)	Maximum survival time (days)	Median survival time (days)	Prolongation in lifespan (%)	P-value
^188Re-liposome	7	333	24	20.75	10.67	0.007
Normal saline	7	None	19	18.75	–	–

Figure 4 The Kaplan–Meier survival curves of Fischer344/F98_luc orthotopic glioma bearing rat model n=7.

Notes: Single intravenous injection of normal saline (•) or 333 MBq ¹⁸⁸Re-liposome (¡) was performed on Day 7 post-inoculation as marked by an arrow.

Abbreviation: d, days.

Figure 5 Tumor growth inhibition monitoring at Day 10, 14, and 17 after treatment with normal saline and ¹⁸⁸Re-liposome, respectively (n=3).

Notes: (A) Photograph of excised tumor masses after treatment with normal saline (left) and ¹⁸⁸Re-liposome (right). (B) Histological examination of H and E staining for tumor parenchyma at Day 14 post-treatment with normal saline (upper) and ¹⁸⁸Re-liposome (bottom). (C) Tumor volume (mm³) growth curve after treatment with normal saline (•) and ¹⁸⁸Re-liposome (○). (D) Tumor weight (mg) growth curve after treatment with normal saline (•) and ¹⁸⁸Re-liposome (○). * and *** indicating the significant differences with P<0.05 and P<0.001 between treated group and control group, respectively.

Abbreviations: d, days; H and E, hematoxylin and eosin.

VredenburghJJDesjardinsAReardonDAThe addition of bevacizumab to standard radiation therapy and temozolomide followed by bevacizumab, temozolomide, and irinotecan for newly diagnosed glioblastomaClin Cancer Res201117124119412421531816

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