The Carcinoma Prostate had been found to involve the skeletal tissues as their preferred metastatic sites during the course of the disease. The metastatic lesions predominantly appear as focal hot spots. In some rare cases they might appear as a Photopenic lesion as well. The focal hot spots showed multiplicity, asymmetrical distribution on both sides of the body in the metastatic involvement. The single Focal hot spot when seen in a bone scan cannot be attributed to the metastatic origin only as it could have been caused by other benign causes as well. The role of imaging in the evaluation of metastatic involvement in Carcinoma Prostate had been described by Langsteger et al. [1]. Hence various methods were resorted to quantify and characterize them. Soloway et al. [2] have classified them by visual inspection method based on the presence and number of focal hotspots as follows. No lesion -0, less than 6 – stage 1, 6 to 20 stage - 2, more than 20 without super scan stage - 3 and Super Scan – Stage 4. The staging by Amico similar but it had not taken the Super Scan appearance into account there by resulting in three stages only. Chylowski [3] proposed a simpler classification into negative, positive and intermediate stages. Dann et al. [4] had measured the 24hr whole body retention as an objective method. Erdi et al. [5] have established a computer analysis based Bone Scan Index using Image segmentation. Noguchi et al. [6] have devised a quantitative evaluation by measuring the percentage area of positive bone scan combining both visual and computer analysis. Elzabeth R Dennis et al. [7] have documented the utility of Bone Scan index as an effective measure of treatment response assessment in Castration resistant Ca. Prostate cases along with the bio-markers. However all these methods could not differentiate between the malignant and benign causes of the focal hot spots in a bone scan. The Temporal scintimetric method of characterizing the Skeletal Hotspots in a bone scan was first reported by Israel et al. [8]. The maximum counts in the focal hotspot in the 24hr Bone scan was divided by the maximum counts in the 4hr bone scan image. He had proved that clear cut differentiation could be established between the degenerative lesions, metastases and the treated metastatic group of patients. However the resultant ratio was in decimal fraction values and no useful cut off values could be derived. Hence it was not accepted for wide clinical usage.

Dr. V. Siva’s retention ratio

In our method the procedure was reversed to get the whole number values. The maximum counts in the Focal hotspot region were obtained by using the region ratio protocol in both the 4hr and 24hr whole body bone scans. The retention ratio was calculated by dividing the 4hr counts by the 24hr counts for the focal hot spot sites. The method of calculating the Dr.V.Siva’s retention ratio is depicted in Figure 1. The whole body total counts in the 4hr and 24hr also were tabulated and the retention ratio was calculated as mentioned above. This scintimetric characterization of the skeletal hotspots had been proved to have different values for the malignant and benign origin by us [9].

Figure 1: Dr. V. Siva’s retention ratio calculation method.

The bone scan was done 4 and 24 hours after intravenous injection of 15 to 25 mCi of Tc99m Methylene Di-Phosponate with adequate hydration using the e-cam Siemens dual head gamma camera with e-cam whole body acquisition protocol in 75 patients with biopsy proven carcinoma prostate. Metastatic involvement was seen in 53 patients and was negative in 22. The Serum PSA levels were obtained from the Patient medical records was tabulated. The 185 focal hotspots in various sites in 34 patients were characterized using the temporal scintimetric method as the 24hr images were not available in the 12 patients of the positive group. Both 4 and 24hr bone scan images were selected using the general display protocol. Then with the help of the region ratio processing protocol the 4 and 24hr anterior and posterior images were selected separately. Maximum counts in the selected regions were then tabulated. Then the 4/ 24hr of Dr. V. Siva’s retention ratio was derived by dividing the 4hr counts with 24hr counts along with the Israel’s 24/ 4hr ratio as well. Then 4/ 24hr Dr. V. Siva’s retention ratio derived by dividing the whole body counts of 4 and 24hr whole body bone scan. The results were compared and analysed.

The details of the Focal hot spot sites, 4hr and 24hr counts, derived 24/ 4hr Israel’s ratio and 4/24hr Dr.V.Siva’s retention ratio values were tabulated and shown in the Table 1.

Table 1: Dr.V.Siva’s retention ratio values.

The mean of 4/24 hr Dr. V. Siva’s retention ratio was found to be 12.32 +/- 3.3 and that of 24/4hr Israel’s ratio to be 0.08 +/- 0.02 in the focal hot spot evaluation. The retention ratios of the focal hotspots and the whole body bone scan total counts obtained were shown in Table 2.

Table 2: Dr. V. Siva’S retention ratio in focal hot spots - Rrfhs & whole body bone scans –Rrwbs.

The 4/24 hr Dr. V. Siva’s retention ratio derived by dividing the whole body counts of 4 and 24hr whole body bone scan was 12.21 +/- 2.78 which was identical to that of the Focal hot spot retention ratio. The serum Total PSA, Free PSA and the %PSA levels in the Bone scan metastasis positive and negative groups were shown in Tables 3 and 4.

Table 3: Serum PSA levels in bone metastasis positive group.

Table 4: PSA level is in bone metastasis negative group.

The Total PSA, Free PSA and the %PSA Values are 61.8, 19.2 and 26.8 in the Metastatic positive group and 34.5, 6.8 and 12.8 in the negative group respectively.

The counts in the focal hotspots represent the osteoblastic activity occurring at that site. The basic mechanism of localization of the radiotracer Tc99m MDP is termed as Chemisorption.

The ionic radius of the Tc99m MDP complex is equal to that of the Calcium -hydroxy appetite crystals. Hence they are adsorbed to the basic building blocks of the skeletal tissue. The retention ratio of benign lesions has been shown to be between 1 to 5 numerical value as the metabolic bone turnover of the skeletal tissue is minimal and constant. Whereas the metastatic and malignant lesion which have increased and rapid metabolic bone turnover due to the underlying disease process always have the numerical value of 10 and above. The fact that the focal hotspot retention ratio and the whole body count retention ratios are identical values confirms the fact that the retention ration is the true representative of skeletal tissue turnover. The student t test evaluation of the focal retention ratio values and the whole body count retention ratio values confirms that there is no significant difference between them as shown in Figure 2.

Figure 2: Focal Hotspot retention ratio vs whole body count retention ratio.

The roles of modern techniques in the detection of Prostate Cancer’s Bone Metastasis have been well narrated and the question about the end of era of bone scan is discussed [10]. The role of serum PSA concentration in determining the need for bone scan was reported by John et al. [11]. The cut of level of serum PSA>8 ng/ ml was mentioned.

The good correlation between the serum PSA levels of >10 ng/ml and the presence of bone metastasis had been documented by Wojcieh Szot [12]. In a study of 1116 it had been proved that the chance of detecting bone metastasis was greater when the srum PSA level was >20 ng/ml by Lojanapiwat et al. [13]. In a study of 48 patients of Ca. Prostate the mean serum PSA level was >109.9 ng/ml in the positive bone metastasis group and it was >54.7 ng/ml in the negative group as documented by Oommen et al. [14]. The serum PSA level in the bone scan positive group was almost TWICE the serum PSA value in the negative bone scan group in this study too as shown by our reported values. Recently the elevated levels of serum miR-141 was shown to be well correlated with bone metastasis in Ca. Prostate patients than the serum PSA levels by Hai-Liang Zhang [15]. This clearly depicts the current situation of lack of implementation of quantitative measurements in the regular practice of bone scan studies.

The current study proves that the skeletal metastatic lesions could be characterised correctly by the non-invasive quantitative Dr.V.Siva’s retention ratio as they show the value to above 10. This will help in the characterization of solitary hotspots as metastatic lesion or not, so that appropriate correct treatment could be decided without resorting to invasive bone biopsy. Similarly the benign degenerative lesion that might be interspersed along with metastatic lesions in a proven case of Carcinoma Prostate could be identified and treated accordingly. However the method is dependent on the correct method of procedure in both 4 and 24hr scans, identical and exact drawing of the region of focal hot spots in both the images for the best results. Any error in these will hamper the outcome of the results. More over this single institutional study must be put to test in more institutions for assessing its universal applicability. It can be concluded that the non-invasive quantitative scintimetric characterization of skeletal metastasis in Carcinoma Prostate patients deserves a place in the proper management protocol.