**4. Physiologic radioiodine uptake**

Following thyroid ablation, physiologic activity is expected in the salivary glands, stomach, breast, oropharynx, nasopharynx, oesophagus, gastrointestinal tract and genitourinary tract.(Ozguven, Ilgan et al. 2004) Physiologic radioiodine accumulation is related to the expression of the NIS and metabolism related to or the retention of excreted iodine. (Bakheet, Hammami et al. 2000; Ahn, Lee et al. 2011) Uptake of radioiodine in the thyroid tissue, salivary gland, stomach, lacrimal sac, nasolacrimal duct and choroid plexus is related to the NIS expression of the cells of the organs.(Morgenstern, Vadysirisack et al. 2005) Ectopic thyroid tissues are found by a variety of embryological maldevelopments of the thyroid gland such as lingual or sublingual thyroid (by failure of migration), a thyroglossal duct (by functioning thyroid tissue in the migration route) and a mediastinal thyroid gland (by excessive migration). Other abnormal migration may produce widely divergent ectopic thyroid tissue in many organs such as liver, oesophagus, trachea, etc. In addition, normal thyroid tissue can be in the ovary (Struma ovarii. It can be classified as uptake in a pathologic lesion.). (Shapiro, Rufini et al. 2000) Ectopic gastric mucosa can be located in the small bowel (Meckel's

imaging and it is known to have higher sensitivity and better contrast resolution than planar imaging. Radioiodine SPECT has higher performance for detecting recurrent lesion compared to planar imaging in thyroidectomized thyroid cancer patients and it also changes

Radioiodine SPECT has excellent capability to detect thyroid cancer tissues, yet the anatomic evaluation of lesion sites with radioiodine uptake remains difficult due to the minimal background uptake of the radioiodine. The performance of SPECT with radioiodine may be further improved by fusing the SPECT and CT images or by using an integrated SPECT/CT system that permits simultaneous anatomic mapping and functional imaging.(Geerlings, van Zuijlen et al.; Spanu, Solinas et al. 2009) The fusion imaging modality can synergistically and significantly improve the diagnostic process and its outcome when compared to a single diagnostic technique. (Von Schulthess and Hany 2008) Therefore, SPECT/CT with radioiodine can demonstrate a higher number of radioiodine uptake lesions, and it can more correctly differentiate between physiologic and pathologic uptakes, and so it permits a more appropriate therapeutic approach to be chosen.(Spanu, Solinas et al. 2009) Despite its many advantages, SPECT/CT cannot be applied for routine use or whole body imaging due to the long scanning time and the additional radiation burden, and so the fusion image should be selected on a personalized basis for those who clinically need the imaging. (Oh, Byun et al. 2011)

PET detects a pair of gamma rays produced by annihilation of a positron which is introduced by a positron emitting radionuclide and this produces three-dimensional image. Owing to its electronic collimation, I-124 PET gives better efficiency and resolution than in I-123 or I-131 SPECT, and so it offers the best image quality. (Rault, Vandenberghe et al. 2007) A fusion imaging modality with I-124 PET and CT can improve the diagnostic efficacy when compared to I-124 PET imaging by the same reasons of SPECT/CT over SEPCT only. I-124 PET/CT has superiority due to the better spatial resolution and faster imaging speed compared to I-123 or I-131 SPECT/CT.(Van Nostrand, Moreau et al. 2010) PET fused with MR is recently being used for research and in clinic fields and it will allow state of art

Following thyroid ablation, physiologic activity is expected in the salivary glands, stomach, breast, oropharynx, nasopharynx, oesophagus, gastrointestinal tract and genitourinary tract.(Ozguven, Ilgan et al. 2004) Physiologic radioiodine accumulation is related to the expression of the NIS and metabolism related to or the retention of excreted iodine. (Bakheet, Hammami et al. 2000; Ahn, Lee et al. 2011) Uptake of radioiodine in the thyroid tissue, salivary gland, stomach, lacrimal sac, nasolacrimal duct and choroid plexus is related to the NIS expression of the cells of the organs.(Morgenstern, Vadysirisack et al. 2005) Ectopic thyroid tissues are found by a variety of embryological maldevelopments of the thyroid gland such as lingual or sublingual thyroid (by failure of migration), a thyroglossal duct (by functioning thyroid tissue in the migration route) and a mediastinal thyroid gland (by excessive migration). Other abnormal migration may produce widely divergent ectopic thyroid tissue in many organs such as liver, oesophagus, trachea, etc. In addition, normal thyroid tissue can be in the ovary (Struma ovarii. It can be classified as uptake in a pathologic lesion.). (Shapiro, Rufini et al. 2000) Ectopic gastric mucosa can be located in the small bowel (Meckel's

**3.3.3 PET (Positron Emission Tomography) or PET/CT imaging** 

the patients' management.

imaging in the near future.

**4. Physiologic radioiodine uptake** 

diverticulum) or terminal oesophagus (Barrett's oesophagus). (Ma, Kuang et al. 2005) The ectopic thyroid and gastric mucosal tissues are able to take up radioiodine.

Uptake of iodine in the liver after radioiodine administration is related to the metabolism of radioiodinated thyroglobulin and thyroid hormones in the organ. The gall bladder also may occasionally be depicted with the biliary excretion of the radioiodine. (Shapiro, Rufini et al. 2000; Carlisle, Lu et al. 2003) A simultaneous hepatobiliary scan with Tc-99m DISIDA (Diisopropyl Iminodiacetic Acid) or mebrofenin is useful for characterizing the gall bladder uptake. Tracer accumulation in the oropharynx, nasopharynx and oesophagus is related to retention of salivary excretion of administered radioiodine.

Visualization of the oesophagus is extremely common and vertical linear uptake in the thorax that is removed by drinking water is characteristic of oesophageal uptake by swallowing of radioactive saliva. The oesophageal activity may also arise from gastric reflux. (Carlisle, Lu et al. 2003) Image acquisition after a drink of water is able to distinguish the activity from mediastinal node metastasis. (Shapiro, Rufini et al. 2000)

Urinary or gastrointestinal anomalies can be responsible for false positive radioiodine uptake. (Ma, Kuang et al. 2005) Visualization of kidney and bladder after radioiodine administration is possible and this is known to be related to the urinary excretion of radioiodine into the urinary collecting system. Administered radioiodine is excreted mainly by the urinary system, and so all dilations, diverticuli and fistulae of the kidney, ureter and bladder may produce radioiodine retention.(Shapiro, Rufini et al. 2000) Visualizing the location of the renal pelvis of ectopic, horseshoe and transplanted kidneys is not usual and radioiodine at the pelvis may lead to misinterpretation. In fact, the renal pelvis and ureter are usually not visualized due to the rapid transit time of the radioiodine. (Bakheet, Hammami et al. 1996) A simultaneous renal scan with Tc-99m DTPA (Diethylene Triamine Pentaacetic Acid) or MAG3 (Mercapto Acetyl Triglycine) is useful for characterizing the urinary tract uptakes. (Shapiro, Rufini et al. 2000) Although the incidence is very uncommon, renal cysts are known to produce radioiodine uptake. The proposed mechanisms for the renal cyst uptake are a communication between the cyst and the urinary tract and radioiodine secretion by the lining epithelium of the cyst. (Shapiro, Rufini et al. 2000)

Tracer accumulation in the colon is very common. Incomplete absorption of the oral radioiodine administration is not considered as the reason of colonic activity due to the lack of colonic activity seen on the early images. Tracer accumulation is probably due to transport of radioiodine into the intestine from the mesenteric circulation and biliary excretion of the metabolites of radioiodinated thyroglobulin. (Hays 1993) Appropriate use of laxatives can be a simple remedy for the activity. (Shapiro, Rufini et al. 2000)

Fig. 3. Physiologic uptake of radioiodine in the nasal cavity, the so called "hot nose". Intense tracer uptake was noted at the thyroid bed area (due to residual thyroid tissue), breast and salivary gland (by the NIS expression of the glands).

Physiologic and False Positive Pathologic Uptakes on Radioiodine Whole Body Scan 11

Fig. 6. Physiologic uptake of radioiodine in both the parotid and submandibular salivary glands. Intense activity in the oral and nasal cavities (by saliva and nasal secretion) was also

anterior posterior

Fig. 7. Physiologic uptake of radioiodine in the breast. Diffuse, moderate radioactivity in the

anterior posterior

breast was noted. There was also noted physiologic tracer uptake in the thyroid bed (suggesting remnant thyroid tissue, which has the NIS expression), salivary glands (by the NIS expression of the glands), stomach (by the NIS expression of the glands), bowel (by secretion of radioiodine into the intestine or biliary excretion of the metabolites of

Fig. 8. Physiologic uptake of radioiodine in the breast. Intense tracer accumulation was noted in both breasts. Physiologic tracer uptake was also noted in the thyroid bed

anterior posterior

radioiodinated proteins) and urinary bladder (by urine activity).

(suggesting remnant thyroid tissue, which has the NIS expression).

noted.

Fig. 4. Physiologic uptake of radioiodine in residual thyroid tissue. Intense tracer uptake was noted at the thyroid bed area due to residual thyroid tissue.

Lactating mammary glands express the NIS, and so the lactating breast shows intense radioiodine uptake that might persist for months after cessation of lactation. Mild to moderate uptake is also seen in non-lactating breast tissue, which can be asymmetrical, presumably owing to the same mechanism that operates in lactation.(Shapiro, Rufini et al. 2000; Tazebay, Wapnir et al. 2000)

Uptake of radioiodine can occur in a residual normal thymus or in thymic hyperplasia and the suggested mechanisms for the uptake are the expression of the NIS in thymic tissues and the iodine concentration by the Hassal's bodies that are present in the thymic tissue, which resemble the follicular cells of the thyroid. Thymic radioiodine uptake is more common in young patients compared to older patients. Even though the incidence is very rare, an intrathymic ectopic thyroid tissue or thyroid cancer metastases to the thymus can be a possible cause of uptake. (Mello, Flamini et al. 2009)

Fig. 5. Physiologic uptake of radioiodine in residual thyroid tissue. Intense tracer uptake was noted at the midline of the upper neck due to residual thyroid tissue in the thyroglossal duct. Mild tracer uptake of the salivary gland (by the NIS expression of the glands) was also noted.

Fig. 4. Physiologic uptake of radioiodine in residual thyroid tissue. Intense tracer uptake

right lateral left lateral

anterior

Lactating mammary glands express the NIS, and so the lactating breast shows intense radioiodine uptake that might persist for months after cessation of lactation. Mild to moderate uptake is also seen in non-lactating breast tissue, which can be asymmetrical, presumably owing to the same mechanism that operates in lactation.(Shapiro, Rufini et al.

posterior

Uptake of radioiodine can occur in a residual normal thymus or in thymic hyperplasia and the suggested mechanisms for the uptake are the expression of the NIS in thymic tissues and the iodine concentration by the Hassal's bodies that are present in the thymic tissue, which resemble the follicular cells of the thyroid. Thymic radioiodine uptake is more common in young patients compared to older patients. Even though the incidence is very rare, an intrathymic ectopic thyroid tissue or thyroid cancer metastases to the thymus can be a

Fig. 5. Physiologic uptake of radioiodine in residual thyroid tissue. Intense tracer uptake was noted at the midline of the upper neck due to residual thyroid tissue in the thyroglossal duct. Mild tracer uptake of the salivary gland (by the NIS expression of the glands) was also noted.

right lateral left lateral

posterior

anterior

was noted at the thyroid bed area due to residual thyroid tissue.

2000; Tazebay, Wapnir et al. 2000)

possible cause of uptake. (Mello, Flamini et al. 2009)

Fig. 6. Physiologic uptake of radioiodine in both the parotid and submandibular salivary glands. Intense activity in the oral and nasal cavities (by saliva and nasal secretion) was also noted.

Fig. 7. Physiologic uptake of radioiodine in the breast. Diffuse, moderate radioactivity in the breast was noted. There was also noted physiologic tracer uptake in the thyroid bed (suggesting remnant thyroid tissue, which has the NIS expression), salivary glands (by the NIS expression of the glands), stomach (by the NIS expression of the glands), bowel (by secretion of radioiodine into the intestine or biliary excretion of the metabolites of radioiodinated proteins) and urinary bladder (by urine activity).

Fig. 8. Physiologic uptake of radioiodine in the breast. Intense tracer accumulation was noted in both breasts. Physiologic tracer uptake was also noted in the thyroid bed (suggesting remnant thyroid tissue, which has the NIS expression).

Physiologic and False Positive Pathologic Uptakes on Radioiodine Whole Body Scan 13

Fig. 12. Physiologic uptake of radioiodine in the thymus. Diffuse, mild radioactivity in the mid-thorax was noted. There was also noted physiologic tracer uptake in the salivary glands (by the NIS expression of the glands) and oral cavity (by saliva containing radioiodine).

right lateral anterior left lateral

Fig. 13. Physiologic uptake of radioiodine in the stomach. Intense tracer uptake was noted at the left upper quadrant of abdomen due to stomach uptake of the tracer. There was also noted tracer uptake in the oral cavity (radioactivity of secreted saliva), salivary gland (by the NIS expression of the glands), thyroid bed (suggesting remnant thyroid tissue, which has

anterior posterior

Fig. 14. Focal radioiodine uptake was noted at the center of the abdomen. The uptake might be related to ectopic gastric mucosa in the Meckel's diverticulum. There was also noted tracer uptake in the stomach (by the NIS expression of the gastric mucosa), oral cavity (radioactivity of the secreted saliva) and salivary gland (by the NIS expression of the glands).

anterior posterior

the NIS expression) and urinary bladder (by urine activity).

Fig. 9. Physiologic uptake of radioiodine in the breast. Focal tracer uptake in the breast was noted. SPECT/CT revealed the accurate location of the breast uptake. Physiologic intense tracer uptake was noted in the thyroid bed (suggesting remnant thyroid tissue, which has the NIS expression) and mild tracer uptake in the liver (by metabolism of radioiodinated thyroglobulin and thyroid hormones).

Fig. 10. Physiologic uptake of radioiodine in the oesophagus. Vertical linear radioactivity in the chest was noted by stagnation of swallowed saliva containing radioiodine. There was also noted physiologic tracer uptake in the thyroid bed area (by residual thyroid tissue) and salivary glands (by the NIS expression of the glands).

Fig. 11. Physiologic uptake of radioiodine in the gall bladder. Intense tracer accumulation was noted at the GB fossa area on the whole body scan and SPECT/CT revealed accurate localization of the uptake. There was also noted physiologic tracer uptake in the thyroid bed area by residual thyroid tissue.

Fig. 9. Physiologic uptake of radioiodine in the breast. Focal tracer uptake in the breast was noted. SPECT/CT revealed the accurate location of the breast uptake. Physiologic intense tracer uptake was noted in the thyroid bed (suggesting remnant thyroid tissue, which has the NIS expression) and mild tracer uptake in the liver (by metabolism of radioiodinated

anterior posterior

anterior CT

Fig. 10. Physiologic uptake of radioiodine in the oesophagus. Vertical linear radioactivity in the chest was noted by stagnation of swallowed saliva containing radioiodine. There was also noted physiologic tracer uptake in the thyroid bed area (by residual thyroid tissue) and

anterior posterior

Fig. 11. Physiologic uptake of radioiodine in the gall bladder. Intense tracer accumulation was noted at the GB fossa area on the whole body scan and SPECT/CT revealed accurate localization of the uptake. There was also noted physiologic tracer uptake in the thyroid bed

CT

thyroglobulin and thyroid hormones).

area by residual thyroid tissue.

salivary glands (by the NIS expression of the glands).

Fig. 12. Physiologic uptake of radioiodine in the thymus. Diffuse, mild radioactivity in the mid-thorax was noted. There was also noted physiologic tracer uptake in the salivary glands (by the NIS expression of the glands) and oral cavity (by saliva containing radioiodine).

Fig. 13. Physiologic uptake of radioiodine in the stomach. Intense tracer uptake was noted at the left upper quadrant of abdomen due to stomach uptake of the tracer. There was also noted tracer uptake in the oral cavity (radioactivity of secreted saliva), salivary gland (by the NIS expression of the glands), thyroid bed (suggesting remnant thyroid tissue, which has the NIS expression) and urinary bladder (by urine activity).

Fig. 14. Focal radioiodine uptake was noted at the center of the abdomen. The uptake might be related to ectopic gastric mucosa in the Meckel's diverticulum. There was also noted tracer uptake in the stomach (by the NIS expression of the gastric mucosa), oral cavity (radioactivity of the secreted saliva) and salivary gland (by the NIS expression of the glands).

Physiologic and False Positive Pathologic Uptakes on Radioiodine Whole Body Scan 15

Fig. 18. Physiologic uptake of radioiodine in a simple cyst of the right kidney. Focal tracer uptake was noted at the right side abdomen. The proposed mechanisms are communication between the cyst and the urinary tract and radioiodine secretion by the lining epithelium of the cyst. There was intense tracer uptake noted in the thyroid bed area (by the remnant tissue of the gland) and mild tracer uptake in the salivary gland (by the NIS expression of

anterior CT right lateral left lateral

(A) (B)

anterior posterior anterior posterior

Fig. 19. Physiologic uptake of radioiodine in the colon. Intense tracer uptake was noted at the colon. The suggested mechanisms for the uptake are transportation of radioiodine into the intestine from the mesenteric circulation and biliary excretion of the metabolites of radioiodinated thyroglobulin or thyroid hormones. There was also noted tracer uptake in (A) the oral cavity (by the radioactivity of secreted saliva), (B) the salivary glands (by the NIS expression of the glands) and stomach (by the NIS expression of the gastric mucosa).

A variety of pathologic lesions producing a false positive radioiodine whole body scan have been reported and contrary to the physiologic uptakes that usually do not create diagnostic confusion, they might be tricky enough to cause some patients to undergo unnecessary fruitless invasive surgical or high dose radioiodine treatment.(Mitchell, Pratt et al. 2000) The not uncommon pathologic lesions showing radioiodine uptake are cystic, inflammatory, non-thyroidal neoplastic diseases. Cystic lesions in various organs can accumulate radioiodine and the mechanism of the uptake is passive diffusion of the tracer into the cysts. Radioiodine accumulation in ovarian, breast and pleuropericardial cysts has been reported.

**5. Pathologic lesions might show false positive radioiodine uptake** 

the glands).

Fig. 15. Physiologic uptake of radioiodine in the lacrimal sac. The uptake is known to be related to active iodine transport by the NIS at the lining epithelium of the sac. There was also noted intense tracer accumulation in the thyroid bed (by remnant tissue of the thyroid, which has the NIS expression) and oral cavity (by the radioactivity of secreted saliva) and minimal tracer uptake in the salivary glands (by the NIS expression of the glands).

Fig. 16. Physiologic uptake of radioiodine in the liver. The uptake is known to be related to metabolism of radioiodinated thyroglobulin and thyroid hormones in the liver. There was also noted intense tracer accumulation in the thyroid bed (by the remnant tissue of the thyroid).

Fig. 17. Physiologic uptake of radioiodine in the urinary bladder. Intense tracer uptake was noted at the suprapubic area by radioactive urine in the bladder. Tracer uptake was noted in the salivary glands (by the NIS expression of the glands) and perineal area (due to urine contamination).

anterior

right lateral left lateral

Fig. 15. Physiologic uptake of radioiodine in the lacrimal sac. The uptake is known to be related to active iodine transport by the NIS at the lining epithelium of the sac. There was also noted intense tracer accumulation in the thyroid bed (by remnant tissue of the thyroid, which has the NIS expression) and oral cavity (by the radioactivity of secreted saliva) and minimal tracer uptake in the salivary glands (by the NIS expression of the glands).

posterior

Fig. 16. Physiologic uptake of radioiodine in the liver. The uptake is known to be related to metabolism of radioiodinated thyroglobulin and thyroid hormones in the liver. There was also noted intense tracer accumulation in the thyroid bed (by the remnant tissue of the

anterior posterior

Fig. 17. Physiologic uptake of radioiodine in the urinary bladder. Intense tracer uptake was noted at the suprapubic area by radioactive urine in the bladder. Tracer uptake was noted in the salivary glands (by the NIS expression of the glands) and perineal area (due to urine

anterior posterior

thyroid).

contamination).

Fig. 18. Physiologic uptake of radioiodine in a simple cyst of the right kidney. Focal tracer uptake was noted at the right side abdomen. The proposed mechanisms are communication between the cyst and the urinary tract and radioiodine secretion by the lining epithelium of the cyst. There was intense tracer uptake noted in the thyroid bed area (by the remnant tissue of the gland) and mild tracer uptake in the salivary gland (by the NIS expression of the glands).

Fig. 19. Physiologic uptake of radioiodine in the colon. Intense tracer uptake was noted at the colon. The suggested mechanisms for the uptake are transportation of radioiodine into the intestine from the mesenteric circulation and biliary excretion of the metabolites of radioiodinated thyroglobulin or thyroid hormones. There was also noted tracer uptake in (A) the oral cavity (by the radioactivity of secreted saliva), (B) the salivary glands (by the NIS expression of the glands) and stomach (by the NIS expression of the gastric mucosa).
