124 I PET/CT in Patients with Differentiated Thyroid Cancer: Clinical and Quantitative Image Analysis

Abstract

Background:

Methods:

The study was designed as a prospective phase II diagnostic trial of patients with confirmed DTC. Following adequate preparation, patients received 2 mCi ¹²⁴I in liquid form and sequential whole-body PET/CT imaging was performed at five time points (2–4 h, 24 ± 6 h, 48 ± 6 h, 72 ± 6 h, and 96 ± 6 h post-administration). All patients who had ¹²⁴I imaging subsequently underwent RAI treatment with ¹³¹I, with administered activities ranging from 100 to 300 mCi. Post-treatment scans were obtained 5–7 days after RAI treatment. A by-patient and by-lesion analysis of the ¹²⁴I images was performed and compared with the post-treatment ¹³¹I scans as well as F-18 FDG PET/CT images. Quantitative image analysis was also performed to determine the total functional volume (mL), activity per functional volume (μCi/mL), and cumulated activity (μCi/h) for remnants, salivary glands, and nodal metastases.

Results:

Fifteen patients (6 women; M _age = 57 years; range 29–91 years) were enrolled into the study. Forty-six distinct lesions were identified in these 15 patients on ¹²⁴I PET/CT images, with a sensitivity of 92.5%. In addition, ¹²⁴I identified 22.5% more foci of RAI-avid lesions compared with the planar ¹³¹I post-treatment scans. This study demonstrates different kinetic profiles for normal thyroid remnants (peaked at 24 h with mono-exponential clearance), salivary glands (peaked at 4 h with bi-exponential clearance), and metastatic lesions (protracted retention), as well as individual variations in functional volumes and thus cumulated activities.

Conclusions:

¹²⁴I PET/CT is a valuable clinical imaging tool/agent, both in determining the extent of disease in the setting of metastatic DTC and in the functional volumetric and kinetic evaluation of target lesions.

Introduction

Although radioactive iodine (RAI) imaging/therapy is one of the earliest applications of theranostics, there remain a number of unresolved clinical questions as to the optimization of diagnostic techniques/protocols as well as improvements in patient-specific treatment planning strategies (1 –9). Current clinical RAI imaging is performed by using either ¹³¹I or ¹²³I. ¹³¹I has a half-life of 8.02 days and has beta (Emax = 606 keV) and gamma (364 keV) emissions. The administered activity is usually 2–5 mCi. The clinical safety/efficacy of higher administered activities has been questioned due to the concern for stunning when it is used just before RAI treatment (10 –12). Although the half-life is suitable for sequential (time course) imaging, the image quality is less than optimal for accurate extent of disease (EOD) evaluation and quantitation. ¹²³I has gamma (159 keV) emissions only. This energy profile is better suited for standard gamma camera imaging, and higher activities can be used with much less concern for stunning. However, the 13-hour half-life does not allow sequential imaging over a period of several days. ¹²⁴I sodium iodide (¹²⁴I) is a positron emission tomography (PET) radiopharmaceutical with a 4.2-day half-life. It potentially offers better imaging characteristics and has a favorable half-life that permits the evaluation of in vivo iodine kinetics. It has a rather complex decay schema, which creates challenges in optimal imaging (13). There exist a number of reports attesting the potential clinical benefits of ¹²⁴I imaging in patients with differentiated thyroid cancer (DTC). However, a uniform clinical protocol for imaging, image analysis, and quantitation has not been firmly established (14 –22).

Study Design

The study was designed as a prospective phase II diagnostic trial with the objectives to determine the imaging characteristics and clinical feasibility of ¹²⁴I PET/computed tomography (CT) imaging for determination of extent of disease and evaluation of RAI kinetics in its physiologic and neoplastic distribution in patients with DTC. Patients with confirmed differentiated (both well-differentiated and poorly differentiated) thyroid cancers were studied. Patients who were newly diagnosed, as well as those who had known or suspected recurrent/metastatic disease, were eligible for the trial. The inclusion criteria for the study included a histological confirmation of DTC and a clinical indication for RAI imaging (detection of known or suspected postoperative residual thyroid bed or nodal disease, extent-of-disease evaluation in known recurrent/metastatic disease, suspicious nodule/mass detected by physical exam, imaging study or fine-needle aspiration, recurrent/metastatic disease suspected by elevated thyroglobulin), age ≥18 years, ability and willingness to give written consent, life expectancy >3 months, and Karnofsky performance status ≥70. Pregnant and nursing women and individuals allergic to iodine were excluded from the study. The study was approved by the Institutional Review Board, and was conducted in accordance with institutional investigational new drug (IND)/research guidelines.

Material and Methods

¹²⁴I sodium iodide

The ¹²⁴I sodium iodide utilized for this study was obtained from IBA Molecular N.A., Inc. It was provided in a 0.02 N aqueous NaOH solution with a radiochemical purity (RCP) >95% iodide, radiochemical impurity <5% (iodate and diiodate), and a radionuclide purity (RNP) >99.9% at calibration. The chemical purity was determined with Tellurium (Te) <1 μg/mL. The RCP and RNP stabilities were verified for 10 days.

¹²⁴I imaging protocol

The administered activity for ¹²⁴I was 2 mCi by oral administration in liquid form. The basic imaging protocol involved a five time-point (2–4 h, 24 ± 6 h, 48 ± 6 h, 72 ± 6 h, and 96 ± 6 h post-administration) whole-body PET/CT imaging schedule. The patients were prepared for RAI imaging/dosimetry either by withholding suppressive thyroxine for an adequate length of time (to achieve a thyrotropin [TSH] level of >50 at the time of imaging) or by administering recombinant human TSH (rhTSH; two consecutive daily doses of 0.9 mg intramuscularly, in the days preceding RAI administration). Two patients in the study cohort were prepared using the rhTSH protocol. These patients underwent ¹²⁴I imaging after receiving the standard two-day rhTSH injections. They received a second set of rhTSH injections for the ¹³¹I treatment. The remaining patients were prepared using the withdrawal protocol. PET/CT scans were performed on a Siemens Biograph Truepoint™ scanner and combined with low-dose CT for attenuation correction and anatomic localization. Scans were obtained from the top of the head to the feet. An acquisition time of 5 min per bed position was used, with iterative 3D reconstruction by four iterations with eight subsets and a Gaussian filter.

¹³¹I imaging protocol

All patients who had ¹²⁴I imaging subsequently underwent RAI treatment with ¹³¹I sodium iodide, with administered activities in the range 100–300 mCi. Post-treatment scans were obtained 5–7 days after RAI treatment. Anterior and posterior planar whole-body scans, as well as static antero-posterior and oblique neck images, were acquired.

Image analysis

The localization of ¹²⁴I in known/suspected lesions, including cervical and remote metastatic sites, was documented. ¹²⁴I images were compared to post-treatment ¹³¹I images. Comparisons were performed on a by-patient and by-lesion basis. All images were reviewed and analyzed by two experienced nuclear medicine physicians. Quantitative image analysis was performed using semiautomatic region of interest (ROI) methodology. The total functional volume (mL), activity per functional volume (μCi/mL), and cumulated activity (μCi/h) for remnants, salivary glands, and nodal metastases were calculated. The ¹²⁴I images were also compared to F-18 FDG PET/CT images that were acquired prior to RAI treatment in all patients. F-18 FDG PET/CT imaging was performed as part of a comprehensive extent of disease evaluation and not for the purpose of this study per se.

Relative sensitivity determination for ¹²⁴I PET/CT versus post-treatment planar ¹³¹I imaging

Comparative image analysis was performed on a by-patient and by-lesion basis. For the purposes of by lesion analysis, any distinct uptake noted on ¹²⁴I PET/CT or post-treatment ¹³¹I planar images was considered “positive reference.” A positive reference implies presence of a tumor/remnant with RAI uptake. The true positive (TP) and false negative (FN) designations, and the sensitivity calculations for ¹²⁴I and ¹³¹I imaging were performed based on the “positive reference.” The sites of physiologic uptake were carefully identified. A physiologic uptake was not considered as false positive (FP). A true negative (TN) designation was used when both ¹²⁴I and ¹³¹I images were negative. The complete chart for TP, TN, FP, and FN designations are explained in Table 1.

Table 1.

Diagnostic Utility Profile for RAI Imaging, and the TP, TN, FP, and FN Designations Based on Disease Detection Profile and Image Characteristics

				Image characteristics
Disease detection profile				¹²⁴ I	¹³¹ I
¹²⁴I (+)	¹³¹I (+)	FDG (±)	Tg (±)	TP	TP
¹²⁴I (+)	¹³¹I (−)	FDG (±)	Tg (±)	TP	FN
¹²⁴I (−)	¹³¹I (+)	FDG (±)	Tg (±)	FN	TP
¹²⁴I (−)	¹³¹I (−)	FDG (−)	Tg (−)	TN NED
¹²⁴I (−)	¹³¹I (−)	FDG (+)	Tg (±)	TN iodine-refractory measurable disease
¹²⁴I (−)	¹³¹I (−)	FDG (−)	Tg (+)	TN iodine-refractory unmeasurable disease

TP, true positive; TN, true negative; FP, false positive; FN, false negative; NED, no evidence of disease; RAI, radioactive iodine; Tg, thyroglobulin.

Results

Fifteen patients (6 women; M _age = 57 years; range 29–91 years) were enrolled into the study. All patients underwent 2 mCi diagnostic ¹²⁴I imaging. All but one patient completed all 5 days of data collection for dosimetry; one patient only completed 2 days of data collection due to personal reasons. Forty-six distinct lesions were identified in 15 patients (11 remnant tissue, 19 metastatic neck nodes, 3 residual neck tumors, 5 metastatic mediastinal/hilar nodes, 5 metastatic lung disease [diffuse micro- or macronodular uptake], and 3 metastatic abdominal tumors). The 46 distinct lesions are the aggregate sum of all the imaging modalities. This number also includes the lesions identified on FDG PET/CT. By virtue of image detail on ¹²⁴I images, the thyroid remnant was further divided into ROIs, including the right and left remnant lobes as well as the pyramidal lobe. These were not separately identified on the post-treatment ¹³¹I scans. FDG PET/CT was clinically indicated and performed in all 15 patients. Therefore, ¹²⁴I PET/CT to FDG PET/CT image comparison was possible in all patients. The FDG(+)/RAI(–) lesions were considered to be functionally dedifferentiated, and were thus stratified as a different biological group, and not considered FN. All patients received therapeutic ¹³¹I, with administered activities ranging from 100 to 300 mCi, and underwent post-treatment imaging.

Remnant uptake and kinetics

There were eight patients with thyroid remnants, status post recent total thyroidectomy (RAI-naive). By-patient analysis indicated that remnant uptake was demonstrated in all of these patients on both ¹²⁴I and ¹³¹I imaging studies. A total of 11 distinct foci of remnant uptake were identified. ¹²⁴I distinctly defined remnant uptake in right lobe, left lobe, and isthmus/pyramidal lobe anatomic sites. ¹²⁴I was positive in 11/11 (100%). ¹³¹I revealed 9/11 (82%) distinct remnant foci. The two missed foci of remnant uptake by ¹³¹I were in the trajectory of the pyramidal lobe in the midline. FDG was negative in all remnant tissue, and none of the thyroid remnants was visually detected as a soft-tissue abnormality on CT. The sequential ¹²⁴I images consistently demonstrated the maximum remnant activity to occur at 24 h. After the peak activity was reached, the clearance was mono-exponential, as shown in Figure 1. The maximum remnant activity ranged from 1.2 to 215.9 μCi, with the total functional remnant volume (the total number of voxels within the remnant ROI) ranging from 1 to 60 mL. The activity per volume of remnant tissue ranged from 0.036 to 11.265 μCi/mL. The total cumulated activity within the remnant ranged from 68 to 12757.3 μCi/h.

FIG. 1.

The uptake and clearance pattern in thyroid remnants. The time–activity curve shows a peak at 24 hours followed by exponential decay.

Salivary gland uptake and kinetics

Physiologic salivary gland activity was demonstrated in all 15 patients, with the activity reaching a peak at 4 h after radioiodine administration. The salivary gland clearance was bi-exponential, with an average of 81% of the activity being cleared from the salivary glands by 24 h.

Nodal disease uptake and kinetics

There were 19 distinct foci of uptake identified as nodal metastasis. ¹²⁴I was positive in 16/19 (84%). ¹³¹I revealed 9/19 (47%) distinct foci of nodal uptake. The three negative nodes by ¹²⁴I were also negative by ¹³¹I but positive on FDG (iodine-refractory nodal disease). Nodal metastatic disease demonstrated a pattern of uptake that was significantly different from the thyroid remnant or physiologic salivary gland activity. A protracted retention was identified as a characteristic pattern for metastatic nodal disease, as shown in Figure 2.

FIG. 2.

The uptake and clearance pattern in lymph node metastasis. The time–activity curve demonstrates a slow upslope to the peak activity with a protracted retention.

Lung disease

There were five cases of metastatic lung disease (2 micronodular, 3 macronodular). One case was negative on both ¹²⁴I and ¹³¹I, but was positive on FDG (iodine-refractory disease). Of the remaining four cases with metastatic lung disease, ¹²⁴I was positive in 1/2 cases with macronodular disease, but was negative in 2/2 cases with micronodular metastatic disease. ¹³¹I post-treatment scans were positive in 4/4 cases. The case of macronodular disease that was negative on ¹²⁴I and positive on ¹³¹I was also positive on FDG and may be in the process of undergoing dedifferentiation.

Abdominal disease

There was only one patient with abdominal disease. This was a very unusual case that presented with metastatic abdominal disease, and no primary was identified in the total thyroidectomy specimen. The disease was discovered at exploratory laparotomy and confirmed by hematoxylin and eosin and immunohistochemistry (for thyroglobulin and TTF-1 staining). A subsequent FDG study showed hepatic, mesenteric nodal, and peritoneal disease. ¹²⁴I demonstrated positive uptake in all abdominal lesions. However, ¹³¹I was only positive in the hepatic disease.

The comparative uptake patterns of ¹²⁴I and ¹³¹I and the overall sensitivity for respective imaging modalities are presented in Tables 2 and 3.

Table 2.

Comparative Diagnostic Efficacy, and By-Lesion Uptake Characteristics of Diagnostic ¹²⁴ I, Post-Treatment ¹³¹ I, and FDG

Lesion definition	¹²⁴ I	¹³¹ I	FDG
Neck, remnant, right	+	+	−
Neck, remnant, left	+	+	−
Neck, remnant, right	+	+	−
Neck, remnant, pyramidal	+	+	−
Neck, remnant, pyramidal	+	−	−
Neck, remnant, midline	+	+	−
Neck, remnant, left	+	−	−
Neck, remnant, left	+	+	−
Neck, remnant, left	+	+	−
Neck, remnant, midline	+	+	−
Neck, remnant, midline	+	+	−
Neck, node, L5, right	+	−	+
Neck, node, L5, right	−	−	+
Neck, node, L5, left	+	−	−
Neck, node, L4, right	−	−	+
Neck, node, L3, right	+	+	−
Neck, node, L3, right	+	−	−
Neck, node, L3, left	+	+	−
Neck, node, L3, left	+	+	+
Neck, node, L2, right	+	−	−
Neck, node, L2, left	−	−	+
Neck, node, L2, left	+	+	−
Neck, node, L2, right	+	−	−
Neck, node, L1, left	+	−	−
Neck, node, L1, left	+	−	−
Neck, L6, left	+	+	−
Neck, L6, left	+	+	−
Neck, L6, left	+	+	−
Neck, L6, left	+	+	−
Neck, L6, midline	+	+	−
Neck, residual disease, left	+	+	+
Neck, residual disease, right	+	+	+
Neck, residual disease, right	+	+	−
Sup med, residual disease, right	+	−	−
Sup med, node, right	+	+	−
Sup med, node, right	+	+	+
Sup med, node, midline	−	−	+
Hilar, node, right	−	−	+
Lung, nodule, right	−	−	+
Lung, micronodular disease, bilat	−	+	−
Lung, micronodular disease, bilat	−	+	+
Lung, macronodular disease, bilat	−	+	+
Lung, macronodular disease, bilat	+	+	−
Abdomen, peritoneal	+	−	+
Abdomen, nodal	+	−	+
Abdomen, liver	+	+	+
	37/46	28/46	16/46

Table 3.

The Comparative Sensitivity Figures for Diagnostic ¹²⁴ I Versus Post-Treatment ¹³¹ I

	TP	TN	FP	FN	Sensitivity
¹²⁴I	37	6	—	3	92.5%
¹³¹I	28	6	—	12	70%

Discussion

This prospective phase II study demonstrates that ¹²⁴I PET/CT imaging is clinically feasible, has high lesion detection sensitivity, and offers an additional advantage of quantitation, which can readily be translated into high-quality dosimetric input (activity determination for absorbed dose calculations). This study is unique in that it utilizes post-treatment ¹³¹I imaging as the gold standard as opposed to routine diagnostic activities of ¹³¹I, which have known limitations in lesion detection.

Van Nostrand et al. compared the ability of diagnostic ¹²⁴I PET/CT images (1.7 mCi) with ¹³¹I planar whole-body imaging (1–2 mCi) in detecting residual thyroid tissue and/or metastatic well-differentiated thyroid cancer. Their data concluded that relative to ¹³¹I planar whole-body imaging, ¹²⁴I PET/CT identified as many as 50% more foci of radioiodine uptake in as many as 32% more patients (23). The present study not only indicates an improved benefit in lesion detectability with ¹²⁴I PET/CT, but also demonstrates its by lesion detection power (sensitivity) when matched against the gold standard of iodine-avid disease, which is a post-treatment ¹³¹I scan after therapeutic doses ranging from 100 to 300 mCi. When using ¹³¹I post-treatment scans as the gold standard, ¹²⁴I PET/CT identified 22.5% more foci of RAI-avid lesions.

The kinetic data derived from the current study demonstrate that normal thyroid remnants, salivary glands, and tumoral lesions (residual cancer tissue and metastatic foci) have different kinetic profiles. Sequential ¹²⁴I images consistently demonstrated that the maximum activity within the thyroid remnant occurs at 24 hours and, after the peak activity is reached, the clearance is mono-exponential. Physiologic salivary gland activity also demonstrated a dependable kinetic pattern reaching a peak at four hours after radioiodine administration and the clearance is bi-exponential. Nodal metastatic disease demonstrated a pattern of uptake that was significantly different from the thyroid remnant or physiologic salivary gland activity. A protracted retention was identified as a characteristic pattern for metastatic nodal disease.

The notable variation in individual kinetic parameters suggests that dosimetry with ¹²⁴I PET/CT could enhance the theranostic value that is always emphasized more than the traditional ¹³¹I methodology. The decision making and selection of appropriate therapeutic activities of ¹³¹I could be more reproducible and accurately determined with ¹²⁴I. It is well known that ¹³¹I has many drawbacks as an imaging agent emitting high-energy 364 keV photons, which are too high for standard nuclear medicine gamma cameras. The low count detection sensitivity resulting from penetration of the crystal and collimator septa by the high-energy photons causes image degradation. These shortcomings of ¹³¹I conventional gamma camera imaging are overcome by the improved spatial resolution of coincidence detection in ¹²⁴I PET/CT. The higher spatial resolution of ¹²⁴I PET/CT is the basis for improved quantitation. Furthermore, the four-day half-life of ¹²⁴I allows for time sequence imaging, which is essential for dosimetry applications. The visual image analysis in this study demonstrated that clinically relevant information as to the extent of disease can be obtained within a 72-hour time period. A future detailed dosimetric analysis will finalize a clinically applicable and logistically feasible protocol (not demanding on patient and physician time and resources).

The present data reveal that on a by-patient basis, the mere presence of remnant tissue can be demonstrated on ¹²⁴I pre-ablation imaging comparable to post-ablation ¹³¹I imaging. However, ¹²⁴I imaging was clearly superior, providing exquisite details in terms of location and laterality of the remnant tissue. High pyramidal lobe remnants were identifiable by ¹²⁴I, but not by ¹³¹I. ¹²⁴I was also superior in the distinction between nodal versus remnant tissue. Perhaps one of the most important findings obtained was the identification of functional thyroid tissue without an anatomic depiction/appreciation of remnant tissue. In all eight patients who had ¹²⁴I imaging performed postoperatively, functional thyroid tissue (remnant) was demonstrated with a measurable functional volume. None of these patients had an anatomically definable volume of tissue by CT imaging in the thyroid bed. The functional remnant volume was different for each lobe (side), in addition to the absolute uptake value at 24 hours, as well as the clearance, and thus the cumulated activity. This finding could challenge the recent trend to utilize fixed and low(er) administered activities to ablate the thyroid remnants (24 –26). Obviously, a larger-scale remnant dosimetry study is required to address this concern.

Diagnostic ¹²⁴I PET/CT imaging failed to demonstrate lung metastases clearly in three patients, two with micronodular disease and one with macronodular disease. All of these cases of lung metastases were detected on the post-treatment ¹³¹I scans. The discrepancy in regards to detection of micronodular lung disease may at least in part be explainable by the fractional uptake that could be under the threshold of detectability/visibility, in the individual nodules from an administered activity of 2 mCi ¹²⁴I. Visibility threshold is defined as adequate activity concentration within a given target volume high enough to be discernable from the background activity. Obviously, the fractional uptake of RAI within a lesion is a function of the NaI symporter (NIS), its expression, and its temporal and spatial functional activity. Taking into consideration the observation of a protracted retention of radioiodine in metastatic lesions and given the process of physical decay, it is possible that these two dynamic processes (in opposing directions) reach the detectability/visibility threshold at different time points. Not only is the administered activity higher for the post-treatment ¹³¹I versus diagnostic ¹²⁴I scans, there is also a 50% difference in physical half-life between the two radiotracers. Therefore, at any reference time point, the relative cumulated activity will be higher with ¹³¹I. In addition, it was observed that there is a progressive increase in activity in metastatic lesions over time. It is postulated that the visibility threshold may not be reached with a 2 mCi administered activity of ¹²⁴I because the point of intersection of the time activity curve for the tumor and the effective half-life curve for ¹²⁴I might remain under the detection threshold.

In one patient, who was proven to have multiple mesenteric/peritoneal nodules by surgical exploration, the pre-treatment ¹²⁴I imaging demonstrated intense uptake in all metastatic lesions. These lesions were not seen on post-treatment ¹³¹I images (which also included SPECT). In this particular patient, a metastatic liver lesion was seen in both imaging modalities (¹²⁴I and ¹³¹I). This perhaps could also be explained by the temporal and spatial functional activity of NIS, which may vary at different metastatic sites or lesions.

The issue of NIS activity has a pivotal importance in the design of the study as well as the data analysis. The functional dedifferentiation process (in thyroid cancers of follicular cell origin) involves downregulation of NIS, and therefore not all thyroid cancer lesions show similar avidity for RAI (27 –29). For this reason, in a strict sense, a FN designation in a given lesion may not (does not) apply. Similarly, other tissues expressing NIS will be positive on RAI imaging, and a FP designation for those does not apply. The sensitivity of ¹²⁴I, as a function of lesion size, is best evaluated by comparison to the post-treatment ¹³¹I scan, which typically is performed with administered activities >100 mCi. A discordance between the two RAI images (¹²⁴I and ¹³¹I) will indicate a different technical performance of the respective radiopharmaceutical/imaging technology. A discordance between RAI images (¹²⁴I or ¹³¹I) and F-18 FDG, on the other hand, will indicate a different functional profile.

¹²⁴I imaging is not without potential technical challenges. The physical characteristics of ¹²⁴I compared with ¹³¹I are summarized in Table 4. One important technical consideration as it directly applies to clinical imaging performance is that ¹²⁴I has a complicated decay schema. First and foremost, ¹²⁴I is not a pure positron emitter. Thus, a potential factor that may degrade image quality is an aberrant source of “true coincidences.” In addition to positron emission, ¹²⁴I has prompt gamma-ray emission that can directly fall within the 511-keV energy window, or down-scatter and result in signal detection within this window. The consequence of prompt gamma-ray emission is that they provide an aberrant source of “true coincidences” when one of the two co-linear 511-keV photons is absorbed or otherwise not detected. However, these coincidences contain no information about the origin of the source decay (30,31). The contribution of this aberrant coincidence detection and its relevance to clinical imaging/dosimetry is yet to be determined.

Table 4.

The Physical Characteristics of ¹²⁴ I Compared with ¹³¹ I

	¹²⁴ I	¹³¹ I
Physical half-life	4.2 days	8.02 days
Emissions	Gamma>90% abundance	Gamma364 keV 81% abundance
	Max energy 603–1691 keV
	Beta +23% abundance	Beta −606 keV max 89% abundance
	Average energy 366–974 keV
Production	Cyclotron	Reactor
Estimated cost	$500/mCi	$5/mCi

Another potentially important technical consideration is the “spillover effect.” The spillover effect can be defined as an apparent gain in activity for small objects or regions. Although partial volume effect and spillover essentially refer to the same physical phenomenon, it is important to distinguish the outcome of these two different effects. For partial volume effect, the apparent loss of activity in the object is distributed across adjacent voxels, which are considered outside the object, resulting in increased activity in these voxels. This increase in activity is referred to as spillover, whereas loss in activity is referred to as partial volume loss (32). In ¹²⁴I PET/CT imaging of thyroid remnants and cancers, this effect could be very important. Remnant tissue, having normal thyroid function, has a preserved capacity of RAI uptake. A very small volume, undiscernible by CT, may have significant uptake of RAI. By virtue of the “spillover” effect, the visible PET activity might be overly exaggerated. In contrast to the remnant tissue, a small metastatic deposit with suppressed uptake function may not be appreciated due to partial volume effect.

Conclusion

In conclusion, ¹²⁴I PET/CT is a valuable clinical imaging tool/agent, in both extent of disease evaluation in the setting of metastatic DTC and in the functional volumetric and kinetic evaluation of target lesions. On a by-lesion and by-patient analysis, ¹²⁴I clearly demonstrated superior clinical characteristics by identifying 22.5% more foci of RAI-avid lesions with a sensitivity of 92.5% (compared with the gold standard ¹³¹I post-treatment scan) and by providing exquisite detail in terms of location and laterality of the remnant thyroid tissue (even when no remnant tissue was appreciated on anatomical imaging). ¹²⁴I, by virtue of being a PET agent, provides discriminating visual image details, which not only facilitate detection and visualization of disease, but also potentially affords quantitative input for accurate dosimetry. The present study demonstrates different kinetic profiles for normal thyroid remnants, salivary glands, and metastatic lesions, as well as individual variations in functional volumes, and thus cumulated activities, which may have implications for treatment planning. The quantitative power of ¹²⁴I PET/CT can be optimized by modifying image acquisition settings and creating indication-specific (remnant vs. disease imaging) protocols.

Footnotes

Acknowledgments

This study was supported by the Simpkins Foundation Grant for thyroid cancer research.

Author Disclosure Statement

None of the study authors has competing financial interests in connection with the submitted manuscript.

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124 I PET/CT in Patients with Differentiated Thyroid Cancer: Clinical and Quantitative Image Analysis

Abstract

Background:

Methods:

Results:

Conclusions:

Introduction

Study Design

Material and Methods

124I sodium iodide

124I imaging protocol

131I imaging protocol

Image analysis

Relative sensitivity determination for 124I PET/CT versus post-treatment planar 131I imaging

Results

Remnant uptake and kinetics

Salivary gland uptake and kinetics

Nodal disease uptake and kinetics

Lung disease

Abdominal disease

Discussion

Conclusion

Footnotes

Acknowledgments

Author Disclosure Statement

References

¹²⁴I sodium iodide

¹²⁴I imaging protocol

¹³¹I imaging protocol

Relative sensitivity determination for ¹²⁴I PET/CT versus post-treatment planar ¹³¹I imaging