**9. Scintimetric characterization of primary tumors by dual phase PETCT study**

The utility and advantage of the dual phase PETCT evaluation in the tumor detection was reported by Kuboto K et al. [41]. The optimal time interval between the early and delayed phase PETCT scans had been proved to be 3 hr. post injection by Chen YM et al. [42]. In our study protocol the delayed PETCT was conducted at 4 hours post injection due to logistic reasons. Rong et al. reported a quantitative estimation to differentiate between the benign and malignant bone lesions using the dual phase PETCT evaluation termed as Rong's Retention Index [43]. The Rong's retention index (RRI), computed as follows:

$$\text{RRI} = \text{(SUVmaxD-SUVmaxE)} \mathbf{X} \ \mathbf{100} \tag{2}$$

Even though there is a noticeable difference between the malignant and benign bone lesions, they also have a major overlap in between.

> Dr.V.Siva's modified Retention ratio SUV max Delayed / SUV max Early X 100 = (3)

We have focused on the clinical and technical aspects of a novel method in this oncologic utility of "Positron Emission Tomography (PET)". In this method, the PET scanner is combined with a CT scanner in a single device [44–47].

In May 2019, this study was conducted among 19 patients aged 9 to 76 years (12 females, 7 males) with a median of 46 ± 18 years with active primary and metabolically lesions of several types of cancers. Permission was taken from each volunteer before they joined the study for delayed 4 h PET/CT scan without injecting F18-FDG any further. The protocol of "F-18 FDG PET image reconstruction and acquisition" was approved by the ethics group and all cases have obtained official consent.

Patients did not drink or eat anything for 4 to 6 hours before IV injection of "F-18 FDG (185 to 375 MBq, i.e. 4 MBq/kg of weight of the body)". Before getting injected, patients received the concentration of serum glucose and all patients had glucose levels below 200 mg/dl. After the injection at 1 hour early and PET/CT scans at 4 hour (delayed) after injection with PET/CT scanner (from PETCT and Wipro GE), the patients settled down in a silent room. The Spiral CT was used for acquiring CT image at 0.75 s per rotation with 4 mm of section thickness, 4 mm of interval, and 40mAs and 120 kVp.

No IV contrast injection was used. We obtained the early images of PET emission from thigh to cranium, usually with 6–7 positions with acquisition of 2 minutes in each bed position. We acquired the images of delayed PET emission of abnormal spots at 4 h after F-18 FDG injection, with 2 minutes of interval between 2 to 3 bed positions. We used the LOR algorithm to reconstruct all PET scans while applying CT-based correction of attenuation. We used the "Advantage 4.7 Volume Viewer"program to obtain the images. The F-18 FDG uptake was evaluated with delayed and early PET images, evaluation of parameters and interpretation of PET image, semi quantitatively. A circular ROI was positioned above the detected bone lesion for semi-quantitative analysis with transverse PET picture.

The ROI was positioned above the whole "F18 FDG lesion" for visualized lesions on PET, including utmost radioactivity. The following formula was used to estimate the "Standardized Uptake Value":

<sup>&</sup>quot;SUV tissue concentration / g /[injected dos = ( *MBq* ) e / body weight g " ( *MBq*) ( )

*Focal Increased Radiopharmaceutical Uptake Differentiation Using Quantitative Indices DOI: http://dx.doi.org/10.5772/intechopen.99065*

For each region of interest, the SUVmax or maximal SUV was calculated in lesion ROI. The variations in the lesions' uptake were measured as retention index:

$$\text{"RI} = \text{(SUVmaxD} - \text{SUVmaxE} ) \times \text{100/SUVmaxE''} \tag{4}$$

Here is the formula to calculate RRI modification by Dr. V. Siva:

$$\text{"RRI} = \text{SUV} \text{maxD} / \text{SUV} \text{maxE} \times \text{100}"\tag{5}$$

The dual time point based quantifications of metabolic uptake rate in 18F-FDG PET had been reported by den Hoff et al. [48]. The potential diagnostic role of dual phase 18F-FDG PETCT scanning was reported by Jones c et al. [49]. This is the first study reporting the findings of the dual phase PETCT in the evaluation and characterization in various primary lesions. The Rong's Retention values showed a wide ranging value and no definite cut off value could be arrived at. But Dr. V. Siva's modification of Rong's Retention Ratio revealed that the cut off value to be 100 and above for confirming the malignant nature of the lesions. The statistical evaluation of the values by Student t Test showed good p value confirming the significance that the two values were significantly different. There is a strong positive correlation in the "Pearson evaluation". It means a high y variable with high x scores and vice versa (**Figure 8**). The inclusion of the various primary malignancies in both the sexes adds advantage to the study. However the non-inclusion of primary benign lesions in the study is the greatest disadvantage. The other limitations being the single institutional study and the small number of patient population.

Scintimetric Characterization of metastatic lymph nodes in various primary malignancies by Dual Phase PETCT study.

In the proven cases of various primary malignancies like Ca. Breast, Ca. Prostate, Lymphomas and alveolar tumors the SUV max values of the metastatic lymph nodes were calculated in both the Early and Delayed phase scans. The PETCT study was performed using the GE Discovery IQ PETCT in those patients with positive lymph node uptake. The early scan was done One hour post injection of 5 to 10 mCi of F18- FDG tracer in the fasting state with their informed consent with optimal serum blood

**Figure 8.** *Pearson correlation coefficient test.*

#### *Radiopharmaceuticals - Current Research for Better Diagnosis and Therapy*

**Figure 9.** *The difference between group 1 Rong's ratio group 2 Dr. V. Siva's modification.*

sugar level of 150 mg/dl. The delayed PETCT was done Four hours after the post injection time with voluntary consent of the patients without any additional injection of the tracer or contrast medium. The SUV max values were obtained utilizing the Advantage 4.4 software provided by the GE. Total of Forty eight lymph nodes at various locations were included in the study. The calculated SUV max values were used to arrive at the Rong's Retention Ratio and the Dr. V. Siva's modification of RRI.

The Rong's retention ratio in the Metastatic lymph nodes group showed the mean value of 37.2 ± 17.0. Dr. V. Siva's modification of the Rong's Ratio showed the mean value of 132.7 ± 19.8. The Dr. V. Siva'a modification of Rong's Retention ratio resulted in the increase in value by 100 with no significant overlap.

In the previous study of dual PETCT scintimentric characterization of the various primary malignancies the Rong's Retention ratio showed the mean value of 35.8 ± 8 and the Dr. V. Siva's modification of RRI showed the mean value of 135 ± 8.1 as reported confirming that the definitive cut of value of 100 and above could be assigned to indicate the malignant and metastatic lesions in the Dual Phase PETCT scans in the Dr. V. Siva's modification method. By eliminating the subtraction of early SUV max value from the delayed SUV max value the negative values were avoided. The statistical analysis of the data using student t test evaluation showed that there is clear cut demarcation between the original Rong's Retention Ratio values and the Dr. V. Siva's modification of Rong's Ratio as shown in the **Figure 9**.

The p value is < 0.0001 indicating the validity of Dr. V. Siva's modification of Rong's Ratio in the Scintimetric characterization of the metastatic lymph nodes of various primary cancers. However the homogeneous population of cancer patients and non-inclusion of the benign lymph nodal enlargement is a definitive limitation of this study. Further evaluation of this concept is warranted as this is a single institutional study of short duration and small number of cases.

#### **10. Conclusions**

The Scintimetric Characterization of the skeletal hot spots helps in the differentiation of benign and malignant lesions that might coexist in a carcinoma prostate patient and treat them accordingly. This has been proved to be useful in the assessment of non healing fractures and pathological fractures as well. The usefulness of this in the evaluation of Rheumatoid Arthritis opens up a new era of research on clinical utilization in both the diagnostic and prognostic aspects of the disease process. The identification and characterization of the diastolic dysfunction directly by applying the Systolic/Diastolic count ration in the gated SPECT myocardial viability studies remains to be explored further.

*Focal Increased Radiopharmaceutical Uptake Differentiation Using Quantitative Indices DOI: http://dx.doi.org/10.5772/intechopen.99065*

The advent and quantification of FDG uptake in a hot spot in the Dual Phase PETCT scan helps in the identification and differentiation of various primary malignant processes and the Metastatic involvement of the lymph nodes. The clinical application of the quantitative indices like the Israel's ratio, Dr. V. Siva's retention ratio in the conventional nuclear medicine studies must see the light of clinical utilization of day to day practice. Similarly in the case of PETCT evaluation of Oncology the utilization of the Rong's retention ratio and the Dr. V. Siva's modification of Rong's Ratio should reach the daily practice mode from the bench [50–52].

## **11. Future perspectives**

In the current era of large volume Data handling and DATAMATIC scenario this quantitative approach will be more suitable for the QBOT establishment for qualitative standardization of the Nuclear Medicine studies [53]. These quantitative indices can be incorporated into the automatic report generation aspect of the Artificial Intelligence in Nuclear medicine as reported by Cumali Aktolun and Felix Nensa [54, 55]. The recent explosion in DATA sciences and ARTIFICIAL INTELLIGENCE provide a new arena worth exploring in the future.

## **Conflict of interest**

The authors declare no conflict of interest.

#### **Notes/thanks**

The authors express their gratitude and fervent references at the divine lotus feet of Bhagawan Sri Sathya Sai Baba varu with whose sole blessings alone this work had become a reality.

### **Author details**

V. Sivasubramaniyan1,2\* and K. Venkataramaniah1

1 Department of Physics, Sri Sathya Sai Institute of Higher Learning, Puttaparthi, Andhra Pradesh, India

2 Department of Nuclear Medicine, Sri Aurobindo Institute of Medical Sciences, Indore, Madhya Pradesh, India

\*Address all correspondence to: drvssm@gmail.com

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
